TAE Trainees Day

TAE Trainees Day A time for trainees to share their knowledge under the supervision of seniors Arranged with the ESCMID Trainee Association, German Society for Infectious Diseases (DGI) & Akademie für Infektionsmedizin

Convenors: K. Adams (Hull, GB)

W.V. Kern (Freiburg, DE)

P. Maver (Ljubljana, SI)

Faculty: K. Adams (Hull, GB)

R. Köck (Münster, DE) S. Stone, B. Cookson (London, GB) – no handout available P.A. Grossi (Varese, IT) K. Graf (Hanover, DE)

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Adams - Welcome and TAE President's address

Trainee Association of ESCMIDTrainees Day 2013

Dr Kate AdamsPresident of TAE

Welcome

• Third Trainees Day Session• The only session at ECCMID dedicated to

trainees• Run in collaboration with the German

Society of Infectious Diseases

• To find out more information – visit our website www.escmid.org/tae,– send an e-mail to [email protected] or – contact us through the discussion forum

http://forum.escmid.org– Fill out your evaluation forms!!

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Adams - Welcome and TAE President's address

Online Quiz

• Running now• Log in through:• Have a go and test your knowledge• Tell a friend• Please fill out the demographic data

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Köck - Hidden dangers: important epidemiological links between infections and animal exposure

Hidden dangers: importantepidemiological links betweeninfections and animal exposure

Robin Koeck, MD

University Hospital Münster

Institute of Hygiene & National Consulting Laboratory for Hemolytic Uremic Syndrome

Münster, Germany

It has been estimated that among 1,415 organisms causing human infections, 61% are zoonotic

direct contact (wounds, sexual contact, vertical transmission, inhalation) 35%

indirect contact (environmental contact, food) 61%

vectors (biting or mechnical transfer by arthropods) 22%

unknown route 6%

also transmissible from human‐to‐human 33%

Main transmission routes:

Fig 1. Among all zoonotic pathogens, x% are…

Classification by infectious agent Classification by reservoir

Salmonellosis, Campylobacteriosis. Anthrax, brucellosis,

verotoxigenicEscherichia coli,

leptospirosis, plague, Q fever, shigellosisand tularaemia

Bacteria

Cysticercosis/Taeniasis trematodosis, echinococcosis/hyd

atidosis, toxoplasmosis and

trichinellosis

Rabies, avian influenza, Crimean‐Congo hemorrhagic fever, Ebola and Rift

Valley fever

Dermatophytoses, sporotrichosis

Parasites

Viruses

Fungi

Adapted from WHO „Zoonoses and veterinary public health”

Ticks, mosquitos, flies

Wild animals(e.g. foxes,

monkeys, apes, birds) and fish

BSE

Prions

Companion animals, horses

Livestock (cattle, pigs, poultry, goats,

sheep)

Rodents (e.g. mice, rats, squirrels, beavers)

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Case report 1

• 31‐year old male; Turkish origin, lives in Germany since 25 years.

• Pulmonary tuberculosis in childhood

• One week pre‐admission: start of diarrhea & fever (up to 38.8°C); diarrhea treated succesfully with loperamide by GP. Origin of diarrhea unknown. Has had fast‐food meals in several „diners“.

• Admission due to paresthesia of the legs and progressive „weakness“

• Paresis of both legs (about 50% of force left); tendinous reflexes were still present

• CSF: leukocyte count of 25 x106/L (25/mm8) (0.62 [62%] lymphocytes, 0.14 [14% monocytes, and 0.24 [24%] polymorphonuclear cells), a total protein level of 0.365 g/L (36.5 mg/dL), and a glucose level of 3.1 mmol/L (56 mg/dL) (simultaneous venous glucose level 4.7 mmol/L [85 mg/dL]).

Data on „classical“ zoonoses in Europe• ECDC/EFSA estimates for cases of zoonotic diseases in 27

European countries in 2010

• Numbers depending on national reporting systems

1. Campylobacter (n=212,064 cases among humans; trend ↑)

2. Salmonella (n= 99,020 cases among humans; trend ↓)

3. Yersinia (n=6,776 cases among humans; trend ↓)

4. EHEC/VTEC infec on (n=4,000 cases among humans; trend ↑)

5. Listeria (n=1,601 cases among humans; trend =)

6. Q‐Fever (n=1,414 cases among humans; trend ↓)

7. Tularaemia (n=807 cases among humans, trend ↓)

8. Echinococcus (n=750 cases among humans; trend ↓)

9. Brucella (n=356 cases among humans; trend ↓)

10. Trichinella (n=223 cases among humans; trend ↓)

11. Mycobacterium bovis (n=133 cases among humans; trend ↑)

12. Congenital toxoplasma infection (n=21 cases among humans; trend =)

13. Rabies (n=2 cases among humans; in animals slightly ↑)

ECDC/EFSA EFSA Journal 2012;10(3):2597

Reservoir: Livestock animals

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Direct professional exposure to livestock

Direct exposure to livestock environment

Exposure to contaminated meat items (ingestion & handling)

Risk factors for transmission between humans and livestock

Poultry

• Salmonella: 1‐2% of the EU breeding flocks are positive (5 target serovars) 6% in laying hen flocks; trends downward.

• Campylobacter: at retail 30% of samples (range 3‐59%) are contaminated

• VTEC / EHEC: 0‐14% (Belgium) of meat samples VTEC positive; 0% positive for VTEC O157.


Pigs

• Salmonella: 0.5‐1% of the animals; 6‐7% of the herds contaminated

• Campylobacter: at retail 0.6% of meat samples contaminated

• VTEC / EHEC: 1‐2% of meat samples VTEC positive; 0‐1% positive for VTEC O157.

• Yersinia: 2‐5% of the meat samples intended to be cooked were contaminated


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Cattle

• Salmonella: 1% of the animals; 8% of the herds contaminated

• Campylobacter: at retail 0.4% of meat samples contaminated

• VTEC / EHEC: 0.5% of meat samples VTEC positive (range 0‐5.4%); 0.1% positive for VTEC O157. Raw‐milk: 3.3% (up to 18% in Germany)


Livestock animals: Wolfs in sheep‘s clothing?

VTEC & food production animals:reliable detection vs. only „eyes of

the crocodile“?

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Case report 2• 4‐year old girl

• Developed initially watery then bloody diarrhea. Origin of diarrhea unknown. Family are cattle farmers; frequently drink raw milk

• Five days after onset of diarrhea: girl develops anemia, thrombocytopenia and acute renal failure

• Stool cultures were positive for Shiga Toxin (by EIA)

Recovery(~90%)

HUS(~10%)

Friedrich et al., Clin. Infect. Dis. 2007Mellmann et al., Clin. Infect. Dis. 2005

‐3 ‐2 ‐1 0 1 2 3 4 5 6 7 8 910

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Watery diarrhea Bloody diarrhea(~60%)

Infection

Large outbreaks caused by EHEC O157:H7

Year Country Cases/HUS/deaths Source Reference

1982 USA 47/0/0 Hamburger* Riley et al., 1983

1992‐93 USA 732/55/4 Hamburger* Bell et al., 1994

1996 Scotland 501/34/20 Meat* Dundas et al., 001

1996 Japan >6000/100/3 Radish sprouts* Watanabe et al., 1996

2000 Canada ~2300/28/7 Drinking water* Hrudey et al., 2003

2005 Sweden 135/11/0 Lettuce Söderström et al., 2005

2006 USA 205/32/1 Spinach* CDC 2006

2006 USA 77/7/0 Iceberg lettuce Sodha et al., 2011

2008 USA 64/2/0 Ground beef Novicki et al., 2010

* strain isolated from the source

EHEC O157:H7 and SF EHEC O157:H-

EHEC Colonies on Sorbitol‐Mac Conkey Agar: EHEC O157:H7 cannot ferment Sorbitol (as most physiological E. coli can)

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EHECStx 1,2 +eae +/‐

STECStx 1,2 positiveeae negative

Mainly colonizing animals Subgroup of Shiga toxin-

producing E. coli (STEC)

380 EHEC serotypes isolated from humans with gastrointestinal disease (O157:H7, non-O157)

42 different strains of HUS-associated E. coli (HUSEC001 –HUSEC042) in Germany

6 confirmed HUS outbreaks in Germany (1988-2010)

EHEC vs STEC

Reliable detection of VTEC in food samples?

EFSA Journal 2009; 7(11):1366, Technical specifications for the monitoring and reporting ofverotoxigenic Escherichia coli (VTEC) on animals and food (VTEC surveys on animals and food)

Normal flora: green = variant susceptible to the selective stimulus; red = resistant to the selective stimulus

Selection process

Selective stimulus: e.g. antibiotics (disinfection, pH, temperature, metals…)

Predominance of resistant variant

Faciliated dissemination (high number of colony forming units) via direct and indirect transmission

Antibiotic use in animals & humans

Animal reservoir of antibiotic resistance

Human reservoir of antibiotic resistance

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ESBL in fecal/rectal samples from cattle, pigs, chickens

UK: 31/48 calves and 2/60 cows carry ESBL‐E. coli. Liebana JCM 2006

China: 3.1% of cattle ESBL‐E. coli positive. Duan RS Micro Drug Resist 2006

Japan: ESBL‐E. coli were in 12.5% of beef cattle. Hiroi M J Vet Med Sci. 2012

France: mastitis cases: 0.4% (6/1427) of E. coli/K. pneumoniae carried an ESBL gene. Dahmen S Vet Microbiol. 2013

Switzerland: 17.1% of fecal samples, mostly calves, ESBL positive. Geser N J Food

Prot 2011

Korea: 1/654 (0.2%) cattle fecal samples was positive for ESBL. Tamang MD

Foodborne Pathog Dis. 2013

Bavaria: n=196/598 (32.8%) ESBL E. coli positive; 39/45 farms 86.7%. Schmid A

Appl Environ Microbiol 2013

UK: ESBL‐E. coli were isolated from 54.5% of the broiler abattoirs and from 3.6% of individual broiler caecal samples . Randall LP JAC 2011

Poland: ESBL in 42.3% of samples from layers, 48.0% from turkey, and 54.5% from broilers. Wasyl D Microb Drug

Resist. 2012

Japan: ESBL‐carrying E. coli were isolated from 60.0% of individual broiler rectal samples, 5.9% of layers. Hiroi M J Vet Med Sci. 2012

Portugal: Cefotaxime‐resistant E. coli were recovered from 32 broiler fecal samples (42.1%). Costa D Vet Microbiol

2009

China: 2% of pigs had ESBL‐E. coli. Duan RS Micro Drug Resist 2006

China: faecal carriage rate of ESBL‐E. coli was 63.6% inpigs. Ho PL J Antimicrob Chemother. 2011

Poland: ESBL in 33.3% of samples from pigs. Wasyl D Microb Drug Resist. 2012

Japan: ESBL‐carrying E. coli in 3% of pigs. Hiroi M J Vet Med Sci. 2012

Czech Republic: 7/118 rectal samples from pigs were positive for ESBL‐E. coli. Bardon J Klin Mikrobiol Infekc Lek 2012

Switzerland: 15.2% of the porcine fecal samples yielded ESBL producers. Geser N J Food Prot 2011

Korea: 21.5% of swine fecal samples ESBL positive. Tamang MD Foodborne Pathog Dis. 2013

MRSA in samples from cattle, pigs, chickens

Belgium: MRSA carriage was 64% in calves, 5% in beef, 1% in dairy cows. Vandendriessche S JAC 2013

Germany: MRSA detected in nasal swabs of cows (7/15) and calves (4/7). Spohr M Zoonoses Public Health 2011

Netherlands: 50% of the beef calvesCarried LA‐MRSA in their nose. Vanderhaeghen W Epidemiol Infect 2010

Belgium: MRSA carriage 3% in broilers. Vandendriessche S JAC 2013

Germany: at farm level 18/20 (90%) of all urkey flocks were MRSA positive. Richter A Epidemiol Infect 2012

Belgium: Broiler flock prevalence 0‐28%. Plentickx LJ Infect Genet Evol. 2011

Netherlands: 7% of all broilers, 35% of all broiler farms MRSA positive. Mulders MN Epidemiol Infect 2010

Prevalence at farm level:

Netherlands: 23‐81% of the farms with MRSA positive pigs. Huijsdens XW Ann Cin Microbiol

Antimicrob 2006, van Duijkeren E Vet Microbiol 2008

Germany: 70% of the farms with MRSA positive pigs. Köck R EJMID 2010

Denmark: 66% of the farms with MRSA positive pigs. Guardabassi L Vet Microbiol 2007

Belgium: 68% of the farms with MRSA positive pigs. Willems G 2nd Symposium on Antimicrobial

Resistance in Animals and the Environment, 2007

Canada: 45% of the farms with MRSA positive pigs. Khanna T Vet Microbiol 2008

MRSA/ESBL contamination in food items at retail

Proportion of MRSA positive food items (%); German national Monitoring of zoonotic food pathogens 2009 and Dutch data (de Boer et al. 2009).

ESBL‐producing enterobacteria:

Chicken: 6‐38% ESBL‐producing enterobacteria positive (Kola A JAC 2012; German

National Institute for Risk Assessment (BfR) Nr. 002/2012 )

Pig meat: 2% ESBL‐E. coli positive (German National Institute for Risk Assessment (BfR) Nr. 002/2012 )

MRSA:

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MRSA in livestock: Relevance for humansBurden of colonization:

•Pig/cattle/Broiler farmers: 6‐86%. (Voss A EID 2005; Denis O Emerg Infect Dis 2009; Köck R Appl Environ Microbiol 2012; Cuny C

PlosOne 2009; Vandendriessche S JAC 2013; Mulders MN Epidemiol Infect 2010)

• Veterinarians: 5%‐45%. (Wulf M EID 2006; Cuny C PlosOne 2009)

• Slaughterhouse staff: 6% (VanCleef BA Epidemiol Infect 2010)

• Family members of pig farmers: 5% (Cuny C PlosOne 2009)

•General population: 0,5% MRSA; LA‐MRSA types rarely in persons without livestock exposure (Köck et al. ICAAC 2012)

Burden of infections:Proportion of livestock‐ass. MRSA types among MRSA from patients in a livestock‐dense region in Germany(Köck R PloSOne 2013)

Increase (0.3% to 5.4% of all MRSA) in LA‐MRSA detection in Germany between 2004‐2011(Schaumburg F JCM 2012)

ESBL in livestock: Relevance for humans

Burden of colonization:

People working with poultry have a higher risk for intestinal carriage of ESBL‐producing bacteria than the general population (30% versus 5%). EFSA Journal 2011;9(8):2322

Burden of infections:

„In a representative sample of human ESBL‐positive E. coli isolates in the Netherlands, 35% contained ESBL genes and 19% contained ESBL genes located on plasmids thatwere genetically indistinguishable from those obtained in poultry isolates.

(Leverstein‐van Hall CMI 2011)

Risk for persons with direct contact seems obvious; risk for consumers of contaminated food items remains controversial

Havelaar AH PlosOne 2010

Diseases transmissible via vectors (mosquitos, ticks…) among „high priority“ zoonoses

Prioritizing of zoonotic diseases in the Netherlands

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Mosquito‐borne transmission

Climate Change mean temperature;extreme temperatures;precipitation;

may have influence on the occurence of both vectors and hosts

GlobalisationInternational travel; International transport; Human population growth /aggregation;

may faciliatate dissemination of vectors / and infected humans

Conclusions

• Huge burden of zoonotic diseases in European countries by livestock / food‐producing animals

• Link between burden of antimicrobial resistance in humans and animals

• Climate change and internationalisation impact on occurrence of vector‐borne diseases

Consider the positive aspects of climate change….

Thank you for your attention

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Grossi - Surgical site infections - ID perspective

Paolo Grossi

SURGICAL SITE INFECTIONS – ID PERSPECTIVE

Infectious & Tropical Diseases UnitDepartment of Transplantation

Ospedale di Circolo e Fondazione Macchi –University of Insubria, Varese,Italy

TAE TRAINEES DAYECCMID 2013 ‐ BERLIN

Clinical presentations of SSTIs

• ~0.1% of adult population requires hospital treatment for SSTIs each year • SSTIs may become complicated if require hospitalisation, surgery, involve

deeper tissues, co-morbidities or systemic symptoms

Eron LJ, et al. J Antimicrob Chemother 2003; 52 Suppl1:i3–17

Skin and soft tissue infections

Infectedulcer

Infectedwound

Diabetic footinfection

Surgical siteinfection

Necrotising SSTI

Cellulitis

Abscess

Surgical Site Infections (SSI)

• Third most common nosocomial infection (14%–16%)

• Most common nosocomial infection among surgical patients (38%)

– 2/3 incisional

– 1/3 organs or spaces accessed during surgery

• 7.3 additional postoperative days at cost of $3,152 in extra charges

Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:250‐278.

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Surgical Site Infection (SSI)

• A surgical site infection is an infection that occurs aftersurgery in the part of the body where the surgery tookplace.

• Surgical site infections can sometimes be superficialinfections involving the skin only.

• Other surgical site infections are more serious and can involve tissues under the skin, organs, or implantedmaterial.

• CDC provides guidelines and tools to the healthcarecommunity to help end surgical site infections and resources to help the public understand these infectionsand take measures to safeguard their own health whenpossible.

Surgical site infections include:

• Those occurring post‐operatively and those severe enough to require surgical intervention for diagnosis and treatment.

• Surgical site infection rarely occurs during the first 48 h after surgery, and fever during that period usually arises from noninfectious or unknown causes.

• In contrast, after 48 h, surgical site infection is a more common source of fever, and careful inspection of the wound is indicated.

• Most SSIs have no clinical manifestations for at least 5 days after the operation, and many may not become apparent for up to 2 weeks.

Surgical site infections• For patients with a temperature <38.5°C and without

tachycardia, observation, dressing changes, or opening the incision site suffices.

• Patients with a temperature >38.5°C or a heart rate >110 beats/min generally require antibiotics as well as opening of the suture line.

• Infections developing after surgical procedures involving nonsterile tissue, such as colonic, vaginal, biliary or respiratory mucosa, may be caused by a combination of aerobic and anaerobic bacteria. These infections can rapidly progress and involve deeper structures than just the skin, such as fascia, fat, or muscle.

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Superficial Incisional SSI: NHSN Definition• Infection occurs within 30 days

after the operation and involves only skin or subcutaneous tissue of the incision with one or more of the following:– Purulent drainage from the

incision;– Positive culture from

superficial incision;– Pain or tenderness, swelling,

erythema, or heat at surgical wound that has been deliberately opened by a surgeon; or

– Diagnosis by a surgeon or attending physician

Subcutaneous tissue

SkinSuperficial incisional SSI

Deep Incisional SSI: NHSN Definition

• Infections involving deep soft tissue (fascia/muscle layers) occurring within 30 days (or up to 1 yr if implant is placed during surgery) after the procedure with one of the following:

– Purulent drainage from deep incision but not from organ space;

– Spontaneous dehiscence or deliberate opening by a surgeon with a positive incision culture or, if not cultured, has the presence of fever or local pain;

– Abscess involving a deep incision found by direct exam, radiologic exam or during reoperation; or

– Diagnosis by a surgeon or attending physician.

Deep soft tissue (fascia & muscle)

Deep incisional SSI

Superficial incisional SSI

Organ/Space SSI : NHSN Definition

• Infections that involve any part of the body opened or manipulated during the operative procedure, excluding skin incision/fascia/muscle layers, within 30 days after procedure (or up to 1 year if implant is placed) with one of the following:– Purulent drainage from a drain that is

placed through a stab wound into the organ/space;

– Positive culture growth of a specimen of tissue or fluid aseptically obtained during operation or aspiration;

– Evidence of infection during surgical procedure or by radiologic or histopathologic examination; or

– Diagnosis by a surgeon or attending physician

Deep incisional SSI

Superficial incisional SSI

Organ/space SSI

Organ/space

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SSI – Risk FactorsOperation Factors

• Duration of surgical scrub• Maintain body temp• Skin antisepsis• Preoperative shaving• Duration of operation• Antimicrobial prophylaxis• Operating room ventilation• Inadequate sterilization of

instruments


• Foreign material at surgical site

• Surgical drains• Surgical technique

– Poor hemostasis– Failure to obliterate dead space

– Tissue trauma

SSI – Risk FactorsPatient Characteristics

• Age

• Diabetes– HbA1C and SSI

– Glucose > 200 mg/dL postoperative period (<48 hours)

• Nicotine use: delays primary wound healing

• Steroid use: controversial

• Malnutrition: no epidemiological association

• Obesity: 20% over ideal body weight


• Prolonged preoperative stay: surrogate of the severity of illness and comorbid conditions

• Preoperative nares colonization with Staphylococcus aureus: significant association

• Perioperative transfusion: controversial

• Coexistent infections at a remote body site

• Altered immune response

SSI – Wound Classification

• Class 1 = Clean

• Class 2 = Clean contaminated

• Class 3 = Contaminated

• Class 4 = Dirty infected

Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:250-278.

Prophylactic antibiotics indicated

Therapeutic antibiotics

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Classification of Operative Wounds by Level of Bacterial Contamination

Surgical Wound Infection Rates According to Wound Class

Wound ClassCruse and Foord

n=62.937SENIC

n = 59352Olson and Lee

n = 36.439Culver et al.n = 84.691

Clean 1.5 2.9 1.3 2.1

Clean-contaminated 7.7 3.9 2.4 3.3

Contaminated 15.2 8.5 7.9 6.4

Dirty and infected 40 12.6 / 7.1

NNIS, 1986-1989

SSSIs etiology

Eron LJ et al. JAC. 2003; 52(suppl 1):i3-i17; Fung HB et al. Drugs, 2003; 63:1459-1480

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Staphylococcus aureusResistance to Oxacillin/Methicillin

EARSS Annual Report 2010

Growing evidence for vancomycin MRSA MIC creep

According to a study at a US medical centre for the period 2000–2004:1

Over 90% of S. aureus isolates had vancomycin MICs <2 μg/ml

The proportion of MSSA and MRSA isolates with vancomycin MIC of 1 µg/ml increased

The proportion of MSSA and MRSA isolates with vancomycin MIC ≤0.5 µg/ml decreased

Several other studies have demonstrated vancomycin MIC creep in MRSA2–7

Increased vancomycin MICs for S. aureus over a 5-year period

80

60

40

20

0

MRSAMSSA

2000 2001 2002 2003 2004

Prop

ortio

n of

isol

ates

with

va

ncom

ycin

MIC

= 1

µg/

ml,

%

Year

1. Wang G et al. J Clin Microbiol 2006;44:3883–38862. Delgado A et al. J Clin Microbiol 2007;45:1325–13293. Rodriguez-Morales AJ et al. Int J Antimicrob Agents

2007;29:607–609

4. Karpadia M et al. ICAAC 2005; Abstract E-807 5. Golan Y et al. IDSA 2006; Abstract LB-116. Zaragoza R et al. ICAAC 2007; Abstract K-7247. De Sanctis J et al. ICAAC 2007; Abstract D-882

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Vancomycin MIC significantly predicts for mortality in MRSA

Soriano A et al. Clin Infect Dis 2008;46:193–200

Treatment group Risk of mortality (OR [95% CI])

P-value

Vancomycin MIC=1 1

Vancomycin MIC=1.5 2.86 (0.87, 9.35) 0.08

Vancomycin MIC=2 6.39 (1.68, 24.3) <0.001

Inappropriate therapy* 3.62 (1.20, 10.9) <0.001

0.5 1 2 5 10

*Inappropriate therapy defined as empirical therapy to which the MRSA strain was resistant

Proportion of Patients with Surgical-Site Infection, According to Type of Infection (Intention-to-Treat Population)

Darouiche RO et al. N Engl J Med 2010;362:18-26

Algorithm for the management and treatment of SSI

Clin Infect Dis 2005;41:1373–406

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Antibiotic choices for incisional surgical site infectionsIDSA Guidelines 2005 (Update in progress)

• Cefoxitin

Intestinal or genital tract

Single agents

CefoxitinCeftizoximeAmpicillin/sulbactamTicarcillin/clavulanatePiperacillin/tazobactamImipenem/cilastatinMeropenemErtapenem

Combination agents

Facultative and aerobic activityFluoroquinoloneThird‐generation cephalosporinAztreonamAminoglycoside

Intestinal or genital tract

Anaerobic activityClindamycinMetronidazoleChloramphenicolPenicillin agent plus ß‐lactamase inhibitor

Nonintestinal

Trunk and extremities away from axilla or perineumOxacillinFirst‐generation cephalosporin

Axillary or perineumAmpicillin/sulbactamOther single agents as described above for intestinal and genital operations

Stevens DL, et al. CID 2005;41: 1373–406

Treatment options for extensively resistantGram‐positive cocci

Drug Approved indications

DaptomycinSSTIBacteremia/Endocarditis

TygecyclineSSTIIAICAP (US)

LinezolidSSTICAPHAP

TelavancincSSTI (US)HAP

CeftarolineSSTICAP

cSSSI: studies 300 and 305cSSSI: studies 300 and 305

Ellis-Grosse EJ et al. Clin Infect Dis 2005; 41(suppl 5):S341-S353

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cSSTI trials: clinical success* inS. aureus infected patients (ME)

85,9

75,069,4

87,0

0

20

40

60

80

100

MSSA (n=405)

–5.6 to 7.8

MRSA (n=64)

–28.5 to 17.4

ME, microbiologically evaluable

Arbeit et al. Clin Infect Dis 2004;38:1673–81

95% CI:

Patie

nts

(%)

*Cure or improvement sufficient to stop antibiotic treatment

DaptomycinComparator

Daptomycin: dosage• In cSSTI: 4 mg/kg once daily• In infective endocarditis/bacteremia 6 mg/kg

• Two minutes infusion recently licensed• No dose adjustment in patients with mild to moderate

hepatic impairment• No dose adjustment in patients with renal impairment

and creatinine clearance (CrCI) ≥30 mL/min• In patients with CrCI <30 mL/min:

– 4-6 mg/kg every 48 hours• In patients on haemodialysis or CAPD

– Administration post-dialysis on dialysis days

Clinical outcomes with daptomycin: success by infection type (ECCMID 2012)

The overall clinical success rate with daptomycin therapy in patients with sepsis was 71% (43% cured and 28% improved)

SSTI, skin and soft tissue infection

Other include : foreign body, septic arthritis, pyleonephritis/UTI, necrotizing infections, necrotizing fasciitis, surgical/non-surgical antibiotic prophylaxis, metastatic abscess

Clinical success: Cure + improved

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Treatment outcome by primary pathogen type (ECCMID 2012)

CoNS, coagulase-negative staphylococci; MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus; CoNS include S. epidermidis and other CoNS; Enterococci include E. faecalis, E. faecium and Enterococcus spp.

Clinical success in patients infected with CoNS and S. aureus was84% (n=49/58) and 72% (n=60/83), respectively

cSSSI: studies 300 and 305cSSSI: studies 300 and 305

Ellis-Grosse EJ et al. Clin Infect Dis 2005; 41(suppl 5):S341-S353

Linezolid (ZYVOX®)

• An oxazolidinone: a novel antimicrobial class

• 100% oral bioavailability

• Equivalent dosing oral/IV

• No dose adjustment in renal failure

• Bacteriostatic

• No cross‐resistance with other antibiotics

• Reversible thrombocytopenia with prolonged use

• Binds selectively to the 50S ribosomal subunit– Inhibits the formation of a functional initiation complex

ZYVOX® (linezolid injection, tablets, and oral suspension) [package insert]. Kalamazoo, Mich: Pharmacia & Upjohn, a Pfizer Company; revised June 2004.

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Linezolid vs Vancomycin in SSI:Clinical Cure Rates at TOC

8798

0

20

40

60

80

100

52/53 47/54

Clin

ical

cur

e ra

te (

%)

Linezolid 600 mg q12h IV/PO Vancomycin 1g q12h IV

P=0.06

-Weigelt J et al.: Am J Surg 2004;188:760-766.

Telavancin versus vancomycin for the treatment of complicated skin and skin‐structure infections associated with surgical procedures

Wilson SE, et al. The American Journal of Surgery (2009) 197, 791‐796

Ceftaroline

Ceftaroline is sometimes referred to as ‘a fifth generation’ cephalosporin because it is active (uniquely for licensed cephalosporins) against MRSA.

It has recently been approved for use in cSSSI and community‐acquired pneumonia by the FDA and by the EMA.

Ceftaroline binds to penicillin‐binding protein (PBP) 2a, an MRSA‐specific PBP that has low affinity for most other beta‐lactamantibacterials, and is active in vitro against MRSA, MR Staphylococcus epidermidis, penicillin‐resistant Streptococcuspneumoniae and vancomycin‐resistant Enterococcus faecalis (not E. faecium), and many Gram‐negative pathogens.

Ceftaroline is inactive against P. aeruginosa and nonfermentors and has no activity against ESBL‐producing Enterobacteriaceae

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Ceftaroline ‐ Dosage• The current dosing regimen used in patients who have

normal renal function in phase 2 and 3 clinical trials is 600 mg i.v. infused for 1 hour every 12 hours.

• Dosage adjustments are not required in the setting of mild renal dysfunction (CrCl >50–80 mL/min) but should be undertaken for patients who have more severe renal dysfunction – CrCl >30–50 mL/min: 400 mg i.v. for 1 hour every 12 hours

– Insufficient data to give specific dosage recommendations for patients with CrCl < 30 mL/min

Clinical response rates of selected baseline isolates at Day 3 (E‐MITT population)

Friedland H.D., et al. AAC Accepts, published online ahead of print on 6.2.2012

Summary

• SSI is a preventable morbidity

• Gram‐positive organisms are the primary pathogens

– MRSA increasing

• Treatment alternatives in MRSA SSIs and cSSTIs

– Vancomycin

– Linezolid

– Daptomycin

– Tigecyclin

– Ceftaroline

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Graf - Surgical site infections - CM perspective

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Documents

TAE Trainees Day