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John Ferguson Infectious Diseases Physician and Microbiologist Newcastle NSW
2019 Part 1 M Med UPNG revision weeks
a An infection which leads to death
b An infection with a SIRS response
c Sepsis in an immunosompromised host
d Sepsis leading to acute organ dysfunction
e An infection plus at least 3 SIRS criteria
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
From the Greek word for ldquoputrefactionrdquo
An exaggerated host response to invasive infection
AKA ldquoblood poisoningrdquo ldquosepticaemiardquo
Infection PLUS a systemic inflammatory response syndrome (SIRS)
Research definition (ACCPSCCM 1992)1
Proven or suspected infection plus SIRS
SIRS=2 or more of
Fever (or hypothermia)
Tachycardia (HRgt90)
Tachypnoea (RRgt20 or PaCO2lt32)
Abnormal white blood cell count (lt4 or gt12)
1 ndash Bone (1992) Chest 1011644
ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction
httpsjamanetworkcomjournalsjamafullarticle2492881
Sepsis = life-threatening organ dysfunction
caused by a dysregulated host response to
infection
Organ dysfunction = an increase in the
Sequential [Sepsis-related] Organ Failure
Assessment (SOFA) score of 2 points or more
Septic shock = subset of sepsis in which hellip
vasopressor requirement to maintain a mean
arterial pressure of 65 mm Hg or greater and
serum lactate level greater than 2 mmolL (gt18 mgdL) in the absence of hypovolemia
httpsjamanetworkcomjournalsjamafullarticle2492881
Martin et al (2003) NEJM 348(16)
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
a An infection which leads to death
b An infection with a SIRS response
c Sepsis in an immunosompromised host
d Sepsis leading to acute organ dysfunction
e An infection plus at least 3 SIRS criteria
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
From the Greek word for ldquoputrefactionrdquo
An exaggerated host response to invasive infection
AKA ldquoblood poisoningrdquo ldquosepticaemiardquo
Infection PLUS a systemic inflammatory response syndrome (SIRS)
Research definition (ACCPSCCM 1992)1
Proven or suspected infection plus SIRS
SIRS=2 or more of
Fever (or hypothermia)
Tachycardia (HRgt90)
Tachypnoea (RRgt20 or PaCO2lt32)
Abnormal white blood cell count (lt4 or gt12)
1 ndash Bone (1992) Chest 1011644
ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction
httpsjamanetworkcomjournalsjamafullarticle2492881
Sepsis = life-threatening organ dysfunction
caused by a dysregulated host response to
infection
Organ dysfunction = an increase in the
Sequential [Sepsis-related] Organ Failure
Assessment (SOFA) score of 2 points or more
Septic shock = subset of sepsis in which hellip
vasopressor requirement to maintain a mean
arterial pressure of 65 mm Hg or greater and
serum lactate level greater than 2 mmolL (gt18 mgdL) in the absence of hypovolemia
httpsjamanetworkcomjournalsjamafullarticle2492881
Martin et al (2003) NEJM 348(16)
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
From the Greek word for ldquoputrefactionrdquo
An exaggerated host response to invasive infection
AKA ldquoblood poisoningrdquo ldquosepticaemiardquo
Infection PLUS a systemic inflammatory response syndrome (SIRS)
Research definition (ACCPSCCM 1992)1
Proven or suspected infection plus SIRS
SIRS=2 or more of
Fever (or hypothermia)
Tachycardia (HRgt90)
Tachypnoea (RRgt20 or PaCO2lt32)
Abnormal white blood cell count (lt4 or gt12)
1 ndash Bone (1992) Chest 1011644
ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction
httpsjamanetworkcomjournalsjamafullarticle2492881
Sepsis = life-threatening organ dysfunction
caused by a dysregulated host response to
infection
Organ dysfunction = an increase in the
Sequential [Sepsis-related] Organ Failure
Assessment (SOFA) score of 2 points or more
Septic shock = subset of sepsis in which hellip
vasopressor requirement to maintain a mean
arterial pressure of 65 mm Hg or greater and
serum lactate level greater than 2 mmolL (gt18 mgdL) in the absence of hypovolemia
httpsjamanetworkcomjournalsjamafullarticle2492881
Martin et al (2003) NEJM 348(16)
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
From the Greek word for ldquoputrefactionrdquo
An exaggerated host response to invasive infection
AKA ldquoblood poisoningrdquo ldquosepticaemiardquo
Infection PLUS a systemic inflammatory response syndrome (SIRS)
Research definition (ACCPSCCM 1992)1
Proven or suspected infection plus SIRS
SIRS=2 or more of
Fever (or hypothermia)
Tachycardia (HRgt90)
Tachypnoea (RRgt20 or PaCO2lt32)
Abnormal white blood cell count (lt4 or gt12)
1 ndash Bone (1992) Chest 1011644
ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction
httpsjamanetworkcomjournalsjamafullarticle2492881
Sepsis = life-threatening organ dysfunction
caused by a dysregulated host response to
infection
Organ dysfunction = an increase in the
Sequential [Sepsis-related] Organ Failure
Assessment (SOFA) score of 2 points or more
Septic shock = subset of sepsis in which hellip
vasopressor requirement to maintain a mean
arterial pressure of 65 mm Hg or greater and
serum lactate level greater than 2 mmolL (gt18 mgdL) in the absence of hypovolemia
httpsjamanetworkcomjournalsjamafullarticle2492881
Martin et al (2003) NEJM 348(16)
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Research definition (ACCPSCCM 1992)1
Proven or suspected infection plus SIRS
SIRS=2 or more of
Fever (or hypothermia)
Tachycardia (HRgt90)
Tachypnoea (RRgt20 or PaCO2lt32)
Abnormal white blood cell count (lt4 or gt12)
1 ndash Bone (1992) Chest 1011644
ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction
httpsjamanetworkcomjournalsjamafullarticle2492881
Sepsis = life-threatening organ dysfunction
caused by a dysregulated host response to
infection
Organ dysfunction = an increase in the
Sequential [Sepsis-related] Organ Failure
Assessment (SOFA) score of 2 points or more
Septic shock = subset of sepsis in which hellip
vasopressor requirement to maintain a mean
arterial pressure of 65 mm Hg or greater and
serum lactate level greater than 2 mmolL (gt18 mgdL) in the absence of hypovolemia
httpsjamanetworkcomjournalsjamafullarticle2492881
Martin et al (2003) NEJM 348(16)
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
ACCPSCCM 1992)1 Severe sepsis= sepsis + organ dysfunction
httpsjamanetworkcomjournalsjamafullarticle2492881
Sepsis = life-threatening organ dysfunction
caused by a dysregulated host response to
infection
Organ dysfunction = an increase in the
Sequential [Sepsis-related] Organ Failure
Assessment (SOFA) score of 2 points or more
Septic shock = subset of sepsis in which hellip
vasopressor requirement to maintain a mean
arterial pressure of 65 mm Hg or greater and
serum lactate level greater than 2 mmolL (gt18 mgdL) in the absence of hypovolemia
httpsjamanetworkcomjournalsjamafullarticle2492881
Martin et al (2003) NEJM 348(16)
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
httpsjamanetworkcomjournalsjamafullarticle2492881
Sepsis = life-threatening organ dysfunction
caused by a dysregulated host response to
infection
Organ dysfunction = an increase in the
Sequential [Sepsis-related] Organ Failure
Assessment (SOFA) score of 2 points or more
Septic shock = subset of sepsis in which hellip
vasopressor requirement to maintain a mean
arterial pressure of 65 mm Hg or greater and
serum lactate level greater than 2 mmolL (gt18 mgdL) in the absence of hypovolemia
httpsjamanetworkcomjournalsjamafullarticle2492881
Martin et al (2003) NEJM 348(16)
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Sepsis = life-threatening organ dysfunction
caused by a dysregulated host response to
infection
Organ dysfunction = an increase in the
Sequential [Sepsis-related] Organ Failure
Assessment (SOFA) score of 2 points or more
Septic shock = subset of sepsis in which hellip
vasopressor requirement to maintain a mean
arterial pressure of 65 mm Hg or greater and
serum lactate level greater than 2 mmolL (gt18 mgdL) in the absence of hypovolemia
httpsjamanetworkcomjournalsjamafullarticle2492881
Martin et al (2003) NEJM 348(16)
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Martin et al (2003) NEJM 348(16)
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Leading cause of death in intensive care Estimated 18 million casesyear
worldwide1
215000 deaths per year in USA 2
Estimated 13000 ICU admissions and 4875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care 71-2
2 Angus (2001) Crit Care Med 291303
3 Finfer (2004) Int Care Med 30589
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
28-day mortality in AustraliaUSA Sepsis 10-30 Severe sepsis 25-40 Septic shock 30-60
Long-term outcomes are even worse
These high mortality rates continue despite Advanced supportive care Aggressive antibiotic and surgical
management of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Community presentation Healthcare associated
bull Urine bull Skinsoft tissue bull Biliary bull Intra-abdominal bull Pneumonia empyaemabull Brain
bull Severe malariabull Severe denguebull Disseminated TB
bull Intravenous linesbull Urinary cathetersbull Post-operative woundsbull Pneumonia (ICU)bull Skin- decubitus ulcers
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Between April 1998 and
March 2000 multi-
resistant enteric gram
negative sepsis occurred
in 106 of 5331 paediatric
admissions (2) but
caused 87 (25) of 353
deaths
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Oct 2007- Oct 2008 57 neonates with Klebsiella infection 23 died 31 multi-drug resistant including to 3 G
cephalosporins
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Severe malaria Dengue shock syndrome
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Incidence of MRSA now high from community and hospital sources (38+)
cf 1990 bacteraemia study by Naraqi et al- no MRSA detected
Lab identification and MRSA detection-must use cefoxitin screen
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Mediators- cytokines and
other products of the
immune response to
infection Often an
exaggerated immune
response harms the patient
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
This is a view of the blood
vessels under the tongue of two
patients
Sublingual lsquoOrthogonal
Polarization Spectralrsquo imaging
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Sorensen (1988)
Large cohort of adult adoptees (960 families) in Denmark
Examined risk of premature death (before age 50) in biological parents vs adopted children
If one biological parent had premature death risk in child
All cause 171
Cancers 119
Infections 452 N Engl J Med 1988 Mar 24318(12)727-32
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
N Engl J Med 1988 Mar 24318(12)727-32Genetic and environmental influences on premature death in adult adopteesSoslashrensen TI1 Nielsen GG Andersen PK Teasdale TWAuthor informationAbstractTo assess genetic and environmental influences on adult mortality we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70 We compared these risks with the adoptees risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70 The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 171 (95 percent confidence interval 114 to 257) for all causes 198 (125 to 312) for natural causes 581 (247 to 137) for infections 452 (132 to 154) for cardiovascular and cerebrovascular causes and 119 (016 to 899) for cancers The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes natural causes and infections 302 (072 to 128) for vascular causes and 516 (120 to 222) for cancers A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70 We conclude that premature death in adults has a strong genetic background--especially death due to infections and vascular causes
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Definitions amp Pathogenesis Burden and causes of sepsis Identifying septic patients patient
assessment Approach to septic patient
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
1 Clinical assessment- origin of patient HIV past medical history including diabetes immunosuppressive medication
2 Laboratory diagnostic testing3 Antibiotics after cultures- as early as possible4 Administer oxygen5 Resuscitation ndash Fluids 6 Source identification and control7 Adequate glycaemic control (keep blood glucose
near normal )8 Consider corticosteroids ndash patients unresponsive to
fluid challenge vasopressors
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Early appropriate RECOGNITION is the key NSW health Sepsis Pathway
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Automated system ndash BACTEC- better media for growing bacteria accommodates larger volume of patientrsquos blood- increases sensitivity
Aseptic collection procedure important to avoid contamination with skin flora
Quicker to become positive ndash usually within 12 hours
Broth is Gram stained and then subcultured
httpsaimednetau20150918maximising-the-value-of-blood-cultures
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Cocci in clumps ndashStaph aureus coagulase negative staph (contaminants usually)
Cocci in chains-streptococci or enterococci
Gram positive rods -clostridia bacillus listeria
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Rods- plump- E coli Klebsiella and similar anaerobic species
Slender rods-pseudomonas
Cocci ndash Neisseria meningitidis (the meningococcus)
Cocco-bacilli -Acinetobacter
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Candida (left) Cryptococcus (right with capsule ndashindia ink preparation) predominantly filamentous moulds very rare
IV line infections (candida)
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Skinsoft tissuebone infection High rates of methicillin-resistant Staphylococcus aureus (MRSA)
PMGH 2016 - 39 to 60 isolate testing as MRSA across adult and paediatric groups inpatient and non-inpatient locations
Implication ndash MRSA resistant to all available betalactam agents ndash eg flucloxacillin amoxycillin+clavulanate ceftriaxone
Pneumonia Streptococcus pneumoniae- benzylpenicillin remains
the mainstay Meningitis
Streptococcus pneumoniae- ceftriaxone (also covers Haemophilus influenzae and Neisseria meningitidis)
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Options
Vancomycin iv ndash given as loading dose 25mgkg (actual body weight) slow infusion (red man syndrome) then twice daily dosage
[Chloramphenicol ivoral
[doxycycline or co-trimoxazole- oral options
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
High mortality- correlated with age of patient higher for MRSA
Define lsquouncomplicatedrsquo and lsquocomplicatedrsquo cases
Risk of relapse up to 3 months later Echocardiogram in the second week of
treatment Minimum 2 weeks IV treatment at
endocarditis doses 4 weeks minimum for complicated cases httpsaimednetau20151015essential-
clinical-care-of-staphylococcus-aureus-bloodstream-infection-sab
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Intra-abdominal biliary urine source infections high mortality especially if treatment delayed
NB 15 of Gram negative (E coli and Klebsiella pneumoniae) isolates were susceptible to chloramphenicol in 2016
Ceftriaxone-resistant isolates (ldquoextended spectrum betalactamaserdquo) are usually resistant to gentamicin cotrimoxazole and ciprofloxacin in POM
Multi-resistant Gram negative sepsis antibiotic options Meropenem (last resort betalactam ndash a carbapenem)
[Fosfomycin (old antibiotic with broad Gram negative spectrum ndash really only practical for urine source infections)
Carbapenemase producing Gram negatives lsquoCPErsquo Colistin (old nephrotoxic IV antibiotic also used via nebulised route)
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Essential Drainage of collections Repair of GIT perforations and lavage of
peritoneum Removal of infected invasive devices- IV lines
pacemakers prosthetic joints
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
SAFE
6997 critically ill
09 Saline vs 4 Albumin
No difference in mortality
Trend to benefit of albumin in sepsis subgroup
OR for mortality 087 [074-102]
aOR for mortality 071 [052-097]
1 SAFE investigators NEJM 3502247
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Most physicians under-fill Fluid overloadpulmonary oedema is easier to
treat than established septic shock
(If there is access to modern ICUs)
Excess fluids potentially hazardous in children
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
httpswwwncbinlmnihgovpubmed27062617
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Annane study 300 refractory septic shock within 8 hours of onset Hydrocortisone 50mg q6h + fludrocortisone 28-Day mortality decreased 55 vs 61 Inadequate adrenal reserve group 53 vs 63
CORTICUS 499 septic shock within 72h (not refractory) Hydrocortisone 50mg q6h 28-Day mortality no change 35 vs 32 Faster reversal of shock 33 vs 58 days No difference according to ldquoadrenal reserverdquo
ADRENAL just reported (2018)
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
httpswwwncbinlmnihgovpubmed29347874
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
There were no significant between-group differences with respect to mortality at 28 days the rate of recurrence of shock the number of days alive and out of the ICU the number of days alive and out of the hospital the recurrence of mechanical ventilation the rate of renal-replacement therapy and the incidence of new-onset bacteremia or fungemia
httpswwwncbinlmnihgovpubmed29347874
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Tight blood sugar control increases mortality Earlier studies suggested benefit1
NICE-SUGAR2
6104 medical and surgical ICU patients
BSL targets 45-6 vs lt10
Mortality 275 vs 249 (plt005)
Severe hypoglycaemia 68 vs 05
1 van den Berghe (2001) 345 1359 2 NICE-SUGAR investigators (2009) NEJM 360 1283
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection
Prevention (infection control reduce unnecessary antibiotic exposure)
Early recognition Early aggressive resuscitation (children beware) Early diagnostics amp antibiotics
Gram negative- gentamicin ciprofloxacin ceftriaxone meropenem hellip (ESBL)
Gram positive ndash benzylpenicillin (S pneumoniae) flucloxacillin (MSSA) vancomycin hellip (MRSA)
Meningitis- ceftriaxone Source control Directed (specific) antibiotic treatment for durations
based on site of infection