Pocket Guide to Diagnosis & Treatment of Ventricular Assist Device (VAD) Infections CLASSIFICATION OF VAD-INFECTIONS Draft Version 1: 1 November 2018 from Hannan M et al. Journal of Heart and Lung Transplantation, 2011 Extravascular Intravascular VAD-specific s Driveline VAD-related s Pericarditis VAD-related bloodstream s other CIED pocket Pocket Mediastinitis Pump/cannula /outflow graft Infective Abbreviations: VAD, ventricular assist device BSI, bloodstream CIED, cardiac implantable electronic device TEE, transesophageal echocardiography P/CVC, peripherical / central venous catheter CIED lead Catheter-related BSI VADunrelated BSI US, ultrasound CT, computertomography PET/CT: 18-Fluodeoxyglucose Positron Emission Tomography/Computed Tomography Copyright: PRO-IMPLANT Foundation (N. Renz, A. Trampuz) and Deutsches Herzzentrum Berlin (E. Potapov, F. Schönrath). The Foundation cannot be held responsible f any treatment failures antibiotic side effects. The latest version of the Pocket Guide is available at: www.pro-implant-foundation.g
DEFINITIONS Extravascular VAD (driveline, pocket) s (A and B fulfilled) Investigation/sign A) Microbiology Negative blood cultures Criteria B) At least 1 criterion fulfilled: Local signs of restricted to the LVAD entry pump pocket site Purulent wound secretion sinus tract abscess (clinical evidence seen in ultrasound and/ CT/PET-CT Microbiology Positive cultures from the skin/subcutaneous tissue Systemic VAD (proven if 2 criteria, probable if 1 criterion fulfilled) Investigation/sign A) Microbiology Criteria Positive blood cultures (time to positivity central/peripheral <2h) and no other focus B) Imaging (TEE, CT- PET-Scan) (either): Pump interi/cannula VAD related Intracardiac mass suspected to be vegetation adjacent to the device Abscess anatomicaly related to device new partial dehiscence of inflow (outflow) cannula Vegetation on native valves Paravalvular abscess C) Extravascular (driveline pump pocket mediastinitis) VAD-related bloodstream (A and B fullfilled) Investigation Criteria A) Microbiology Positive blood cultures (differential time to positivity central/peripheral <2h) B) Imaging Negative echocardiography and no other focus
CLASSIFICATION accding to time of occurrence Pathogenesis Perioperative Acute (immature biofilm) <4 weeks after surgery (early) Chronic (mature biofilm) 4 weeks after surgery (delayed/low-grade) Hematogenous contiguous Treatment strategy Antimicrobial therapy <3 weeks of symptom duration Eradication Biofilm-active (if available) 3 weeks of symptom duration Suppression, treatment of exacerbation No biofilm-active antibiotics, suppression DIAGNOSTIC WORK-UP All patients with suspected LVAD : C-reactive protein (CRP) and white blood cell count Echocardiography (transesophageal, TEE) Blood cultures: At least 3 sets within 24h 2 from peripheral sites If central line in place: 1 central and peripheral culture at same time Chest X-ray CT PET-CT* leukocyte scintigraphy** Specific situations: If local : aspiration of pus at driveline exit site/pocket abscess, swab of driveline exit site Sonication of retrieved hardware/catheter, if removed In culture-negative s consider molecular diagnostics (e.g. PCR, NGS) *18-FDG-PET/CT: sensitivity of 90-100% and specificity of 67-80% were repted f qualitative (visual) analysis 1-3. False-positive results may occur within approx. 6 months after implantation. **Leukocyte scintigraphy if no PET/CT available (less sensitive but me specific than PET-CT 3 ) and at least 3-6 months after surgery. 1 Dell Aquila et al, Ann Thacic Surg, 2016, 2 Dell Aquila et al, European Heart Journal - Cardiovascular Imaging, 2018, 3 De Vaugelade et al, Journal of Nuclear Cardiology, 2018 Note: many of the recommendations are based on expert opinion because rigous clinical data are not available and the likelihood that clinical trials will be conducted to answer some of these questions is low. Our goal was to develop guidelines that offer a practical and useful approach to assist practicing clinicians in the management of VAD-s. F individual recommendations contact our Consultation Ptal at: cp.pro-implant-foundation.g
DIAGNOSTIC ALGORITHM Suspected VAD Blood cultures (2-3 sets) Blood cultures positive Antibiotic pretreatment? Blood cultures negative Imaging (TEE, (PET-)CT, US) Local signs of abscess/fluid collection seen in imaging in US/CT none negative Central line in place and time to positivity >2h apart? no yes positive CIED pocket (if in place) VAD pocket positive PET-CT Negative Evidence of other focus? yes Catheterrelated LVAD-unrelated BSI VAD Driveline Infection unlikely, close follow-up no CT/PET-CT CIED-associated BSI? positive Intracardiac mass/abscess new partial dehiscence of in- /outflow cannula Vegetation on valve Vegetation on CIED lead VAD pump/cannula-associated VAD-associated CIED-associated
TREATMENT OF VAD-SPECIFIC INFECTIONS Infection Surgery Antimicrobial treatment Acute Chronic Local VAD s Pocket Surgical debridement, wrapping with omental latissimus dsi flap 6 weeks of biofilmactive treatment* (eradication) 2-4 weeks, consider suppressive treatment** Driveline Surgical debridement percutaneous drainage, if abscess. Driveline relocation Consider listing f high urgent transplantation 6 weeks of biofilmactive treatment* (eradication) 2-4 weeks of antibiotic treatment, consider local use of antibiotics Systemic VAD s Pump/ cannula s Surgical debridement Pump exchange after tempary intravascular VAD suppt Consider listing f high urgent transplantation 12 weeks of biofilm-active treatment* (eradication) Infection Surgery Antimicrobial treatment Bloodstream s 4-6 weeks, consider suppressive treatment** * Attention to drug interactions between rifampin and comedication (particularly warfarin other vitamin k antagonists) is required. ** Consider suppression (until transplantation lifelong), if bacteremia persists despite removal of device (CIED/catheter) and adequate treatment if relapse occurs after adequate treatment TREATMENT OF VAD-RELATED INFECTIONS Catheter-related Endocarditis CIED-lead vegetation VAD-related Removal of catheter Removal/exchange of CIED No surgery (consider listing f high urgent transplantation) Accding to guidelines f catheterrelated BSI Accding to CIED Pocket Guide, consider suppressive treatment 6 weeks of antimicrobial therapy followed by suppressive treatment * TREATMENT OF OTHER INFECTIONS Infection Surgery Antimicrobial treatment VAD-unrelated BSI None Treatment accding to primary focus
ANTIMICROBIAL TREATMENT Empirical intravenous treatment Ampicillin/sulbactam 3-4x3g amoxicillin/clavulanic acid 3-4x2.2g (higher dose, if systemic ) + vancomycin 2x15mg/kg daptomycin 1x10mg/kg if patient septic polymicrobial possible: add gentamicin 1x240mg i.v. if patient is allergic to penicillin: cefazolin 4x2 ( meropenem 3x2g, ifanaphylaxis) if fungal suspected: add caspofungin 1x70mg (reduce dose to 50mg from day 2, if patient weighs <80kg) Local/extravascular s Intravenous treatment Suppression (al) Eradication (al) Staphylococcus spp. Oxacillin-susceptible Anaphylactic reaction to penicillins methicillin-resistant Streptococcus spp. Penicillin-susceptible Anaphylactic reaction to penicillin penicillin-resistant Flucloxacillin 4x2g Cefazolin 3x2g Vancomycin 2x15mg/kg Daptomycin 1x 6-8mg/kg Penicillin G 4x5 Mio E Ceftriaxon 1x2g Vancomycin 2x15mg/kg Daptomycin 1x 6-8mg/kg Cotrimoxazol 2x960mg Clindamycin 3x600mg Doxycyclin 2x100mg Amoxicillin/clavulanic acid 3x1g Amoxicillin 3x1g Clindamycin 3x600mg Levofloxacin 2x500mg Rifampin 1 2x450mg Levofloxacin 2x500mg Cotrimoxazol 3x960mg Doxycyclin 2x100mg Amoxicillin 3x1g Clindamycin 3x600mg Levofloxacin 2x500mg Enterococcus spp. Penicillin- and gentamicin (HL)- susceptible Amoxicillin 4x2g 2 ( gentamicin 1x3 mg/kg, if device in situ) Amoxicillin 3x1g Linezolid 2x600mg Amoxicillin 3x1g Linezolid 2x600mg Anaphylactic reaction to penicillins penicillin-resistant Enterobacteriaceae Anaphylactic reaction to penicillin/cephalosp Vancomycin 2x15mg/kg Daptomycin 1x10mg/kg ( gentamicin 1x3 mg/kg, if device in situ) Ceftriaxon 1x2g Piperacillin/tazobactam 3x4.5g Ciprofloxacin 2-3x400mg meropenem 3x1g Cotrimoxazol 2x960mg Ciprofloxacin 2x750mg Ciprofloxacin 2x750mg (if resistant to ciprofloxacin, consider long-term suppression) 1 Attention ins to drug interactions between rifampin and other drugs metabolized through CYP-3A4 and CYP-2C9 (particularly warfarin) is required. 2 ampicillin 6x2g i.v.
Systemic VAD s Staphylococcus spp. Oxacillin-susceptible Anaphylactic reaction to penicillins methicillinresistant 1 Streptococcus spp. Penicillin-susceptible Anaphylactic reaction to penicillins penicillinresistant Enterococcus spp. Penicillin- and gentamicin (HL)-susceptible Penicillin- suscpetible and gentamicin (HL)-resistant (only E. faecalis) Anaphylactic reaction to penicillins penicillinresistant enterococci Enterobacteriaceae Anaphylactic reaction to penicillins/cephalospins Candida spp. Intravenous treatment (suppression) Flucloxacillin 6x2g Cefazolin 3x2g Vancomycin 2 2x15mg/kg Daptomycin 1x 8-10mg/kg Penicillin G 4x5 Mio E Amoxicillin 6x2g Ceftriaxon 1x2g Vancomycin 2 2x15mg/kg Daptomycin 1x 8-10mg/kg Amoxicillin ampicillin 6x2g Amoxicillin Ampicillin 6x2g Ceftriaxon 2x2g Vancomycin 2 2x15mg/kg Daptomycin 1x10mg/kg Fosfomycin 3x5g Ceftriaxon 1x2g Ciprofloxacin 2-3x400mg meropenem 3x1g Amphotericin B (liposomal) 1x 3-5mg/kg Caspofungin 1x50-70 mg Anidulafungin 1x200 mg Intravenous treatment (eradication) Add Rifampin 3 2x450mg p.o. to regimen in the left column Add Gentamicin 2 1x 3mg/kg to regimen in the left column Amoxicillin ampicillin 6x2g Amoxicillin ampicillin 6x2g Ceftriaxon 2x2g Vancomycin 2 2x15mg/kg Daptomycin 1x10mg/kg Fosfomycin 3x5g Replace gentamicin with Ciprofloxacin 2x750mg p.o. to regimen in the left column Fluconazol 1x400-800mg p.o. (consider suppression f 1 year) 1 In MRSA accding to MIC f vancomycin: if 0.5mg/L: vancomycin, if 1mg/l: daptomycin 2 Adjustment accding to through level: gentamicin: target <1 mg/l; vancomycin: target 15-20mg/l) 3 Check drug interactions between rifampin and other drugs (particularly warfarin, vit k antagonists)
MANAGEMENT OF BACTEREMIA IN VAD-RECIPIENTS (extrapolated and modified after DeSimone et al. Heart Rhythm 2016 (f CIED)) Positive BC in patient with VAD (without signs of pocket inflammation) Gram-negative rods Gram-positive bacteria, Candida Treat primary source (routine TEE is not needed) other CoNS, enterococci, streptococci, Candida S. aureus Treat biofilm-active f 6 weeks (preemptive use) No surveillance BC necessary - + TEE + Treat as f endocarditi s (PVE) TEE - Treat primary source/ bacteremia (2-4weeks) Treat biofilm-active to complete 6 weeks (preemptive use) no No alternative source Positive BC >72h Device revision <3 months Positive PET/CT yes Surveillance BC 2-4 weeks after stopping antibiotics Relapse of bacteremia? Treat as VAD-related (despite negative TEE) Suppression BC, blood cultures, TEE, transthacic echocardiography, CoNS, coagulase-negative staphylococci