bacterial infections in hemodialysis patients sandra a. kemmerly, md, macp, fidsa 26 june, 2015...

Bacterial Infections in Hemodialysis Patients Sandra A. Kemmerly, MD, MACP, FIDSA 26 June, 2015 Pathogenesis and Prevention

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

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

Annual Death Rate due to Sepsis in HD Patients Kidney International, Vol. 67, 2005

Pathogenesis of Bacteremia in Hemodialysis Patients (HD)

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

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

Lymphocytes

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

The Hemodialysis Procedure Disruption of skin barrier during access Dialysis water treatment system Dialyzer reuse

CVC used in Hemodialysis Non-tunneled Tunneled Implantable

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

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

Arteriovenous Fistula

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

Proper Insertion of Central Line

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

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

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

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

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

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

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

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

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

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

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

Causes of Diabetic Foot Lesions Ischemia from macroangiopathy (ischemic foot) Microangiopathy (neuropathic foot) Neuropathy with loss of sensory, autonomous and motor innervation

Mechanisms leading to the diabetic foot lesion. MICHAEL SCHMIG et al. JASN 2000;11:1153-1159 2000 by American Society of Nephrology

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

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)

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

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

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

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

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

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

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

Radiographic studies: Plain xray Scans CT MRI Culture of organisms: bone (definitive) blood, joint fluid sinus tract Diagnosing Osteomyelitis

Microbiology: Overview Type of osteo Organism(s ) hematogenousage - dependent contiguous focusmixed (staph, GNR) vascular insufficiencymixed (GPC -strep, Staph, GNR - Psa, anaerobes) puncture wound = pseudomonas

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

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

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)

99mTc and Gallium Scans

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

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

T 1 image; enhancement of calcaneal bone marrow

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

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

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

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

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

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

Pathogens in Pneumonia S.pneumoniae H. influenzae S.aureus Gram-negative rods Work up: Gram stain and culture Consider use of fluoroquinolones empirically

Urinary Tract Infection Asymptomatic pyuria and bacturia ~30% ESRD patients Does not require treatment Gram-negative bacteremia Urine may be orgin Systemic antibiotics required

bacterial infections in hemodialysis patients sandra a. kemmerly, md, macp, fidsa 26 june, 2015...

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