Pocket Guide to Diagsis & Treatment of Cardiovascular Implantable Electronic Device (CIED) Infections Draft Version : November 208 DEFINITION Pocket infection, if all 4 criteria are fulfilled: Investigation/sign Local signs of infection and/ microbiology (at least one of them) Fever rigs Blood cultures (2-3 sets) Criteria Local signs of inflammation Purulent wound secretion sinus tract abscess Wound dehiscence implant on view (generat subcutaneous leads) Positive culture 3 from pocket tissue explanted CIED Absent Negative TEE No vegetations on leads 2 valves Erythema, swelling, warmth, pain tenderness 2 Fibrous strands visible of older leads seen in TEE may represent aseptic thrombus, especially if blood cultures are negative (without antimicrobial therapy) 3 F highly virulent ganisms (e.g. S. aureus, E. coli) one positive culture needed, f low-virulent ganisms (e.g. S. epidermidis, C. acnes) 2 me positive cultures are needed to confirm infection Systemic CIED infection, if criterion is fulfilled: Device-associated endocarditis (intraveus leads) Pocket infection with positive blood cultures Positive TEE (with lead valve vegetation) with positive blood cultures Positive blood cultures with gram-positive bacteria Candida spp. at two different occasions without evidence of infectious focus ptal of entry (e.g. intravascular catheter) Infective endocarditis defined by modified Duke criteria Device-associated mediastinitis pericarditis (epicardial leads) F individual recommendations contact our Consultation Ptal at: cp.pro-implant-foundation.g Copyright: PRO-IMPLANT Foundation (N. Renz, A. Trampuz) and Deutsches Herzzentrum Berlin (F. Schönrath, Ch. Starck). The Pocket Guide follows international recommendations. The Foundation cant be held responsible f any treatment failures antibiotic side effects. The latest version of the Pocket Guide is available at: www.proimplant-foundation.g
Intraoperative diagstics including pocket swab, tissue culture, +/- lead tip culture and device sonication. Consider molecular diagstisc in culture-negative cases. If lead extraction is too risky, consider isolated generat exchange with consecutive lifelong antimicrobial suppression. MANAGEMENT ALGORITHM POCKET INFECTION Local signs of infection Fever/rigs? Blood cultures positive current antibiotic treatment? TEE positive? Pocket infection confirmed Assess f systemic infection Superficial (erythema, stitch abscess) Deep (dehiscence, draining pus, deep abscess, pocket discomft) Within 30 days of implantation? Early postimplantation inflammation / infection Remove entire CIED and antimicrobial treatment Antimicrobial treatment with/without debridement and retention of CIED Clinical response? Close follow-up observation
Suspected systemic CIEDinfection Fever/rigs (unexplained) Unexplained bacteremia Evidence of distant seeding MANAGEMENT ALGORITHM SYSTEMIC CIED INFECTION Blood cultures ( 2 sets) TEE Assess f pocket infection TEE positive? Blood cultures positive? If pretreated: stopp Repeat blood cultures and follow-up closely Staphylococcus aureus Coagulase-negative staphylococci Cutibacterium spp. Candida spp. Streptococcus spp. (viridans group, betahemolytic) Enterococcus spp. Systemic CIED infection confirmed 2 cultures positive and/ other source excluded? Gram-negative bacteria Streptococcus pneumoniae Remove entire CIED 2 Treat with antimicrobials accding to endocarditis guidelines Collect surveillance blood cultures (after 48-72 h) If persistent indication f CIED see Treatment algithm f CIED infections Treat bloodstream infection Closely follow-up after discontinuation of e.g. hematogeus seeding of mitral atic valve, spondylodiscitis, joints, liver, and spleen, lungs 2 Intraoperative diagstics, including pocket swab, tissue culture, lead tip culture, sonication of the device
SURGICAL PROCEDURES FOR CIED INFECTIONS Pocket infection d = days week 5 weeks Debridement & retention 6 weeks Debridement & removal 4 d 0 d -2 weeks One-stage exchange (contralateral side) 4 d 0 d -2 weeks Two-stage exchange (ipsilateral side) 4 d 0 d 4 weeks 4 weeks Systemic infection 4-6 weeks (endocarditis treatment) Debridement & removal 2-6 weeks individual* 2-4 weeks Two stage exchange 6-8 weeks 2 * Interval individual, as follows: if valve lead vegetation visible: >72 h after negative blood cultures following device removal If valve vegetation: >4 d after negative blood cultures following device removal Duration of antimicrobial treatment: TEE negative: S. aureus 2-4 weeks, other pathogens 2 weeks; TEE positive: valve vegetation: 4-6 weeks f S. aureus, enterococci, n-hacek gram-negative bacteria; 4 weeks f streptococci (2 weeks in combination with gentamicin in high susceptibility to penicillin), HACEK; lead vegetation and hematogeus seeding: 6 weeks, uncomplicated lead vegetation: 2-4 weeks 2 At least 6 weeks (4 weeks after reimplantation) analogous to prosthetic valve endocarditis: if valve vegetation present, early switch after 2-4 weeks i.v. to al treatment possible; in persistant bacteremia after removal, treat accding to endocarditis guidelines Debridement Explantation of device Exchange of device Reimplantation of device i.v. al with biofilm activity al without biofilm activity
No surgery 2 w eeks TREATMENT ALGORITHM FOR CIED INFECTIONS Pocket infection Early superficial infection (<30 days)? Debridement & retention of device 6 weeks (biofilmactive) One-stage exchange of device (contralatera l side) 2 weeks CIED-dependency? Two-stage exchange (ipsilateral side) reimplantation as soon as soft tissue is cured 4 weeks after reimplantaion (biofilm-active) Débridement & removal 2 weeks f pocket infections Endocarditis treatment (NVE) f systemic infection Systemic CIED infection Remove entire CIED CIED-dependency? Valve vegetation BC, blood cultures, TEE transesophageal echocardiography, both examination befe removal of CIED TEE+, BC + TEE -, BC + Reimplantation once BC after removal are negative f > 4 days Endocarditis treatment (as PVE 4 weeks after reimplantation, in total 6 weeks) Lead vegetation Reimplantation once BC after removal are negative f > 3 days Endocarditis treatment (as PVE after reimplantation) 2-4 weeks (S. aureus 4 weeks)
ANTIMICROBIAL TREATMENT Empirical intraveus treatment Ampicillin/sulbactam 3-4x3g amoxicillin/clavulanic acid 3-4x2.2g (higher dose, if systemic infection) + vancomycin 2x5mg/kg daptomycin x0mg/kg if patient septic polymicrobial infection possible: add gentamicin x240mg i.v. (adapt to body weight) if patient is allergic to penicillin: cefazolin 4x2 ( meropenem 3x2g, if anaphylaxis) if fungal infection suspected: add caspofungin x70mg Pocket infections Intraveus treatment Oral treatment ( device in situ) Oral treatment (with device in situ) 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 2x5mg/kg Daptomycin x 6-8mg/kg Penicillin G 4x5 Mio E Ceftriaxon x2g Vancomycin 2x5mg/kg Daptomycin x 6-8mg/kg Cotrimoxazol 2x960mg Clindamycin 3x600mg Doxycyclin 2x00mg Amoxicillin/clavulanic acid 3xg Amoxicillin 3xg Clindamycin 3x600mg Levofloxacin 2x500mg Rifampin 2x450mg Levofloxacin 2x500mg Cotrimoxazol 3x960mg Doxycyclin 2x00mg Amoxicillin 3xg Clindamycin 3x600mg Levofloxacin 2x500mg Enterococcus spp. Penicillin- and gentamicin (HL)- susceptible Amoxicillin 4x2g 3 ( gentamicin x3 mg/kg, if device in situ) Amoxicillin 3xg Linezolid 2x600mg Amoxicillin 3xg Linezolid 2x600mg Anaphylactic reaction to penicillins penicillin-resistant Vancomycin 2x5mg/kg Daptomycin x0mg/kg ( gentamicin x3 mg/kg, if device in situ) Enterobacteriaceae Anaphylactic reaction to penicillin/cephalosp ins Ceftriaxon x2g Piperacillin/tazobactam 3x4.5g Ciprofloxacin 2-3x400mg meropenem 3xg Cotrimoxazol 2x960mg Ciprofloxacin 2x750mg Ciprofloxacin 2x750mg (if resistant to ciprofloxacin, consider long-term suppression)
Systemic CIED infections Staphylococcus spp. Oxacillin-susceptible Anaphylactic reaction to penicillins methicillinresistant Intraveus treatment after device removal (befe reimplantation) Flucloxacillin 6x2g Cefazolin 3x2g Vancomycin 2 2x5mg/kg Daptomycin x 8-0mg/kg Intraveus treatment after reimplantation Add Rifampin 2x450mg p.o. to regimen in the left column 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 Penicillin G 4x5 Mio E Amoxicillin 6x2g Ceftriaxon x2g Vancomycin 2 2x5mg/kg Daptomycin x 8-0mg/kg Amoxicillin 6x2g 3 Gentamicin 2 x3mg/kg Amoxicillin 6x2g 3 Ceftriaxon 2x2g Vancomycin 2 2x5mg/kg Daptomycin x0mg/kg Gentamicin 2 x3mg/kg Fosfomycin 3x5g Ceftriaxon x2g Gentamicin 2 x3mg/kg Add Gentamicin 2 x 3mg/kg to regimen in the left column Amoxicillin 6x2g 3 Gentamicin 2 x3mg/kg Amoxicillin 6x2g 3 Ceftriaxon 2x2g Vancomycin 2 2x5mg/kg Daptomycin x0mg/kg Gentamicin 2 x3mg/kg Fosfomycin 3x5g Replace gentamicin with Ciprofloxacin 2x750mg p.o. Anaphylactic reaction to penicillins/cephalospins Candida spp. Ciprofloxacin 2-3x400mg meropenem 3xg Amphotericin B (liposomal) x 3-5mg/kg Caspofungin x50 mg Anidulafungin x200 mg to regimen in the left column Fluconazol x400-800mg p.o. (consider suppression f year) In MRSA accding to MIC f vancomycin: if 0.5mg/L: vancomycin, if mg/l: daptomycin 2 Adjustment accding to through level: gentamicin: target < mg/l; vancomycin: target 5-20mg/l) 3 ampicillin 6x2g i.v.
MANAGEMENT OF BACTEREMIA IN CIED-CARRIERS (modified after DeSimone et al. Heart Rhythm 206) Positive BC in patient with CIED (without signs of pocket inflammation) Gram-negative rods Gram-positive cocci Treat primary source (routine TEE is t needed) No routine follow-up BC (unless suspect of infection relapse) other CoNS, enterococci S. aureus - + TEE Remove CIED + TEE - Treat primary source/ bacteremia (2-4weeks) Surveillance BC 2-4 weeks after stopping No alternative source Positive BC >72h Device revision <3 months Positive PET/CT Relapse of bacteremia? Remove CIED Accuracy of PET/CT f pocket infection: sensitivity 96%, specificity 97%; f systemic infection: sensitivity 76%, specificity 83% (Mahmood M., J Nucl Cardiol 207) BC, blood cultures, TEE, transthacic echocardiography, CoNS, coagulase-negative staphylococci