Bacterial Infections in Hemodialysis Patients Sandra A. Kemmerly, MD, MACP, FIDSA 26 June, 2015...
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- Slide 1
- Bacterial Infections in Hemodialysis Patients Sandra A.
Kemmerly, MD, MACP, FIDSA 26 June, 2015 Pathogenesis and
Prevention
- Slide 2
- Disclosure of Financial Relationship Sandra Kemmerly, Has no
relationships with any entity producing, marketing, re-selling, or
distributing health care goods or services consumed by, or used on,
patients
- Slide 3
- End Stage Renal Disease (ESDR) Bacterial infections common in
Hemodialysis (HD) patients Infection is second leading cause of
death ESDR patients Cardiovascular disease is 1 st Septicemia in HD
patients rose 51% from 1991-1999 Hospitalization for septicemia
results in Increased risk of myocardial infarction CHF Stoke
Peripheral vascular disease Evidence suggest HD patients have
higher incidence of infective endocarditis (IE) J Am Soc Nephrol
15:1038-1045, 2004 Nephrol Dial Transplant 19: 1360-1362, 2004
- Slide 4
- Annual Death Rate due to Sepsis in HD Patients Kidney
International, Vol. 67, 2005
- Slide 5
- Pathogenesis of Bacteremia in Hemodialysis Patients (HD)
- Slide 6
- Pathogenesis of Bacteremia in HD Patients Impaired Host
Immunity Factors Malnutrition Trace element deficiencies Iron
overload Impaired glucose metabolism Dialysis uremia Neutrophil
dysfunction Impaired chemotaxis Oxidative metabolism Phagocytic
activity Degranulation Intracellular killing apoptosis
- Slide 7
- Pathogenesis of Bacteremia in HD Patients Impaired Host
Immunity Abnormalities in cell-mediated immunity Primarily involves
T-lymphocytes Lymphocytopenia Impaired delayed skin reactivity
Decreased in vitro lymphocute proliferation Alterations in
B-lymphocyte function Affects humoral immunity Decreased
immunoglobulin levels Depressed antibody response to antigens
Dysregulation of cytokine synthesis Impaired macrophage receptor
function
- Slide 8
- Lymphocytes
- Slide 9
- Bacterial Virulence and Adherence Factors Expression of
virulence genes for bacterial survival Proteases, superoxide
dismutase, catalase inhibits bacterial killing Bacteria form SLIME
matrix Extracellular polysaccharides Biofilm Acts as barrier
between antibiotic and bacteria More likely with foreign surfaces
(central venous catheters) S.aureus adheres to host proteins on
fibronectin (CVC) Coagulase-negative staphylococci onto polymer
surface
- Slide 10
- The Hemodialysis Procedure Disruption of skin barrier during
access Dialysis water treatment system Dialyzer reuse
- Slide 11
- CVC used in Hemodialysis Non-tunneled Tunneled Implantable
- Slide 12
- Use of Vascular Access Catheters Non-tunneled: 1-2 weeks
Tunneled: months to years Fistula (AVF) 8-12 weeks to mature Graft
(AVG) 2-6 weeks after placement
- Slide 13
- Hemodialysis Vascular Access Device (HVAD) Infections
Thrombosis and infection most frequent cause of access failure
Simple arteriovenous fistula (AVF) preferred device for chronic
dialsyis >70% functional after 3 years Infection rate is on 2-3%
over life of AVF Limitations: exhaustion of arteries and veins to
create anastamosis, development of venous aneurysms, stenosis
Alternative: polytetrafluroroethylene synthetic (Gortex) Not as
durable, 3 yr survival rate is 50% Thrombectomy or revision can
repair the AVG
- Slide 14
- Arteriovenous Fistula
- Slide 15
- Cuffed Central Line Catheters Only use when no other limb
option Should be placed in OR as they are tunneled with protective
cuff More prone to infection the the AVF or AVG Rate of bacteremia
2 times that of AVG Temporary CVC bedside catheters should be
placed in right internal jugular or subclavian vein as bridge 30
days maximum recommendation Approximately removed due to
infection
- Slide 16
- Proper Insertion of Central Line
- Slide 17
- Hemodialysis Vascular Access Device (HVAD) Infections Most
common cause of infection in HD population Erythema / cellulitis
Skin breakdown Purulent drainage Bleeding Fever, drainage, abscess
< 50% cases Organisms: S.aureus, coagulase-negative
staphylococcus, gram- negative rods
- Slide 18
- Bacteremia in HD Patients HVAD responsible for half of
infections resulting in bacteremia S.aureus can lead to metastatic
soft tissue, bone infection and endocarditis Suggest TEE MSSA:
cefazolin or nafcillin MRSA: vancomycin, daptomycin, linezolide +/-
gentamicin or rifamipin Minimal treatment course 4 weeks if NO
endocarditis
- Slide 19
- Causes of Catheter-related Blood Stream Infections Colonization
of cutaneous catheter tract and tip with skin flora Intraluminal
colonization due to contamination of the hub Hematogenous seeding
to the catheter from another focus of infection Intraluminal
contamination with solvent or infusate
- Slide 20
- Prevention of Infections Central lines higher risk than fistula
or graft Promote fistula use Get catheters out Improve catheter
care Clean hands before and after every patient contact Teach
patients about good vascular access care
- Slide 21
- Catheter Care Exit site examination Aseptic technique Cleans
HUB Mask / eye protection Fresh sterile gloves Hub scrubbed with
CHG, alcohol, or provodine-iodine Immediate connection Same
procedure for disconnection Exit-site care After each HD session
for gauze/tape Every 7 days for transparent dressing
- Slide 22
- Emerging Bacterial Resistance Increasing MRSA, VRE in US
dialysis centers Colonization of VRE associated with outpt use of
vancomycin Some strains of VISA Vancomycin intermediate S.aureus
Black: MRSA Gray: VRE Source: US national surveillance of
dialysis-associated disease
- Slide 23
- Fever During Hemodialysis Must be aggressively evaluated
Indolent vascular access infection Blood cultures Usual organisms:
graft infection Waterborne organisms: contamination of water source
Burkholderia, Stenotrophomonas, Pseudomonas, Aeromas spp
- Slide 24
- Fever in HD: Empiric Antibiotics Empiric therapy should be
initiated Antibiotics post-dialysis Cefazolin, in absence of
methicillin resistance for gram- positive organisms Cefoxitin or
Ceftazidime and aminoglycosides for gram- negative organisms
Reserve vancomycin unless septic, previously documented MRSA
infection Minimize spread of vanc-resistant gram-positive
organisms
- Slide 25
- The Diabetic Foot in the Dialyzed Patient Independent risk fact
for foot ulceration 5 fold higher in dialysis-treated patients
Amputation, peripheral arterial disease, prior ulcer, neuropathy ~
2 fold higher Contributing factors Physical and psychological
health Mobility Manual dexterity Visual acuity Nutrition Leg edema
and neuropathy anemia Diabetes Care, vol 33, no 8, 2010
- Slide 26
- Diabetic Foot Infections Bacteria gain entry to subcutaneous
tissue by disruption of the normal cutaneous barrier Small fissures
between toes Traumatic wounds Burns Chronic pressure ulcers
Infection can be mild and localized Can spread rapidly via tendon
sheaths and fascial planes Abscesses in plantar spaces can begin
under a metatarsal head
- Slide 27
- Epidemiology of Foot Lesions in Diabetic Patients with Renal
Disease Rate of lower limb amputation with renal failure secondary
to diabetic nephropathy is ~14% 10 times higher than the diabetic
population at large 10% of new HD patients have already had above
or below-ankle amputation J Am Soc Nephrol 11: 2000
- Slide 28
- Causes of Diabetic Foot Lesions Ischemia from macroangiopathy
(ischemic foot) Microangiopathy (neuropathic foot) Neuropathy with
loss of sensory, autonomous and motor innervation
- Slide 29
- Mechanisms leading to the diabetic foot lesion. MICHAEL SCHMIG
et al. JASN 2000;11:1153-1159 2000 by American Society of
Nephrology
- Slide 30
- Diabetic Foot Lesions Ischemic Painful Foot cold, cyanotic,
atropic Foot pulses absent Sensation UNIMPAIRED Atrophy of
intrinsic foot muscles Acral necrosis Tip of toe, heel Neuropathic
Painless Foot warm, pink, dry Foot pulses present Sensation
IMPAIRED Atrophy of subcutaneous fat, necrosis under callus or
metatarsal ulcer
- Slide 31
- Examination of Diabetic Foot Lesions History of trauma
Inspection of shoes and stockings Inspection for callus formation,
interdigitial mycosis, necrosis, ulcers Neurologic exam (relexes,
perception of vibration, pedography Angiologic exam (Doppler
pressures ankle and toe) Angiography only prior to interventions
X-rays (2 planes)
- Slide 32
- Microbiology 1980s and early 1990s virtually all considered
polymicrobial Gram positive, gram negative and anaerobes Recent
studies have demonstrated monomicrobial, similar to non-diabetic
patients with skin and soft tissue infections S.aureus and
streptococcal species Chronic infections, previously treated can be
polymicrobial S.aureus, streptococci (Group B), Enterocoocus,
E.coli, Klebsiella, Proteus, Pseudomonas
- Slide 33
- Changing Microbiology Increasing isolation of
multidrug-resistant organisms (MDROs) MRSA Associated with higher
rate of treatment failure Panton-Valentine leukocidin virulence
factor Extended-spectrum beta-lactamase (ESBL)-producing strains of
Enterobacteriaceae Microbiologic sampling Tissue cultures,
curettage or biopsy
- Slide 34
- DrugsClassMRSA activityB.fragilis activity Dose adjustment for
renal impairment Ampicillin/ sulbactam -lactam/- lactamase
inhibitor NoYes Ticarcillin/ clavulanate -lactam/- lactamase
inhibitor NoYesyes Pip/tazo-lactam/- lactamase inhibitor NoYes
Imp/cilistatinCarbapenemNoYes ErtapenemCarbapenemNoYes
MoxifloxacinQuinoloneNoYesNo TigecyclineGlycylcyclcineYes No
VancomycinGlycopeptideYesNoYes LinezolidOxaxolidinoneYesNo
DaptomycinCyclic lipopeptide YesNoYes
- Slide 35
- Acute Management of Diabetic Gangrene Control infection Assess
need for revascularization Assess need for amputation Provide
long-term adequate foot care and foot wear to prevent
recurrences
- Slide 36
- Treatment Strategies with Gangrene Treatment Decide if high
amputation is necessary Bed rest (unloading foot) Control of
hyperglycemia Surgical debridement Culture of exudative material
Parenteral antibiotics If indicated Revascularization Resection of
exostoses, metatarsal heads Patience Wait for demarcation before
amputation if possible
- Slide 37
- Patient Prophylactic Measures for Prevention Avoid walking
barefoot to prevent trauma Avoid tight footwear Orthopedic shoes to
relieve pressure on deformed foot Correct trimming of toenails
Corns treated by physician or podiatrist Treat fungal infections
topically Foot powder for sweaty feet Lanolin ointment for dry skin
Inspect feet daily Exercise daily to improve collateral blood
flood
- Slide 38
- Osteomyelitis of Foot with Diabetes Contiguous spread from soft
tissue Takes days to weeks Uncommon in acute infection 20% of
diabetic foot infections have underlying bone involvement Some
studies suggest up to 2/3 Increases treatment failure and
amputations
- Slide 39
- Radiographic studies: Plain xray Scans CT MRI Culture of
organisms: bone (definitive) blood, joint fluid sinus tract
Diagnosing Osteomyelitis
- Slide 40
- Microbiology: Overview Type of osteo Organism(s )
hematogenousage - dependent contiguous focusmixed (staph, GNR)
vascular insufficiencymixed (GPC -strep, Staph, GNR - Psa,
anaerobes) puncture wound = pseudomonas
- Slide 41
- Plain X-rays In general, osteomyelitis must extend 1 cm &
compromise 30 - 50% of bone mineral content to produce noticeable
changes in plain radiographs. Findings: Osteopenia, periosteal
elevation Endosteal scalloping Loss of trabecular architecture
- Slide 42
- Slide 43
- Radionuclide Studies Technesium bone scan: (3 phase ) positive
earliest (48 hrs after infection) positive in inflammation and new
bone formation Can detect multifocal osteo Pooled
sensitivity/specificity 81% / 28% not useful after surgery (+ up to
2 years) negative scan in highly-suspected cases may indicate lack
of blood flow to area
- Slide 44
- Gallium and Indium Scanning Gallium scans: does not show bone
detail well, hard to tell from soft tissue, also positive in
metastatic disease 99mTc uptake < gallium infection 99mTc uptake
> gallium reactive Indium scans: positive in 40% of acute &
60% of chronic osteo, negative in areas of new bone formation
Pooled sensitivity / specificity 74% / 68% Better for diabetic feet
infections (no red marrow)
- Slide 45
- 99mTc and Gallium Scans
- Slide 46
- Slide 47
- CT Scanning Picks up early disease ( marrow density) Defines
extent of disease areas of necrosis/abscess/sinus tracts *Superior
to x-ray and MRI for bony margins and showing sequestrae and
involucrum helpful in planning surgical approach utility if metal
in place False (+)s: stress fractures, osteoid osteomas
- Slide 48
- Slide 49
- MR Scanning Good for distinguishing bone vs soft tissue/joint
Osteomyelitis: excellent - detecting abnormal bone marrow signal on
T-1 and signal on T-2 postsurgical/post-traumatic scarring:
decreased signal on T-1 and no impact on T-2
Sensitivity/specificity 90-100%/ 80% False (+)s: fractures,
tumors
- Slide 50
- Slide 51
- T 1 image; enhancement of calcaneal bone marrow
- Slide 52
- Contiguous Focus & Vascular Insufficiency Osteomyelitis
Symptoms can be delayed for > a month Low-grade fever, pain over
joint Local signs: redness, swelling Loss of bone stability May/
may not be painless (neuropathy) Frequently ulcer, drainage Fever
and sepsis often absent
- Slide 53
- Slide 54
- Vascular Insufficiency Osteo: Treatment Cover for staph aureus
MSSA vs MRSA Gram-negative coverage: Pseudomonal cephalosporins,
pip-tazo Quinolones, ampicillin-sulbactam carbapenems Anaerobic
coverage: MetronidazoleClindamycin Beta-lactamsMoxifloxacin
- Slide 55
- Bone Levels for Selected Antibiotics Drug % levels in bone
Ampicillin 10-33 Ceftriaxone, ceftaz; cefipime 20; 27; 100
Imipenem; meropenem26-40; 17 Pip/tazo20-25 Vancomycin (serum level
>35) 30 (sternal); axial less Cipro; levofloxacin; moxi27-48;
38-99; 27-49 Linezolid37-50 Clindamycin40-67 TMP-SMX50/15
Metronidazole79-100
- Slide 56
- Use of Newer Antibiotics Linezolid: Data not high quality, is
accumulating Compassionate use; N= 89; gram (+) infections Cure
rate ~80%; including MRSA & VRE w/ surgery/graft removal
Daptomycin: EU-CORE registry report N = 220 (114 no prosthesis); 28
d Rx; S. aureus 33%, coag-neg Staph 32% 55% had other Abxic (Qs or
penems); 52% had surgery Overall - Success 75% - 23% cured, 52%
improved Telavancin, dalbavancin, oritavancin no data
- Slide 57
- Duration of Antibiotic Therapy Clinical situationRoute of
therapyDuration of therapy No residual infected tissue (e.g. post-
amputation) Parenteral or oral2-5 days Residual infected soft
tissue (but not bone) Parenteral or oral2-4 weeks Residual infected
(but viable bone) Initial parenteral, then consider oral switch 4-6
weeks No surgery, or residual dead bone postoperatively Initial
parenteral, then consider oral switch > 3 months Clin infect Dis
39, 2004
- Slide 58
- Pneumonia Common in patients with ESRD CXR: variable and can be
misleading Pulmonary edema Metastasis Fungal disease Predisposing
conditions Underlying cardiac disease Pulmonary fluid overload Low
albumin Suboptimal response from pneumonia and flu vaccines
- Slide 59
- Pathogens in Pneumonia S.pneumoniae H. influenzae S.aureus
Gram-negative rods Work up: Gram stain and culture Consider use of
fluoroquinolones empirically
- Slide 60
- Urinary Tract Infection Asymptomatic pyuria and bacturia ~30%
ESRD patients Does not require treatment Gram-negative bacteremia
Urine may be orgin Systemic antibiotics required
- Slide 61