Pocket Guide to Diagnosis & Treatment of Vascular Graft Infections (VGI)

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Pocket Guide to Diagsis & Treatment of Vascular Graft Infections (VGI) DEFINITION Investigation /sign Local signs of infection Histopathology Microbiology Definitive Criteria Purulent wound secretion sinus tract abscess Wound dehiscence graft on view Atoenteric fistula Intraoperative gross purulence Evidence of infection in peiprosthetic tissue Positive culture from specimen taken at the immediate area around the graft Continuous bacteremia 2 in the presence of a graft with other infectious focus Positive sonication fluid culture of removed graft Imaging Abscess involving the graft and the surrounding tissue in CT/MRI PET-CT Failure of the graft to incropate into surrounding soft tissue Draft Version : September 208 Infection confirmed, if definitive criterion 2 suggestive criteria fulfilled: Suggestive criteria GI Bleeding Single positive culture Perigraft air fluid in CT persisting f me than 8-2 weeks postoperatively Lockal thickening of the intestinal wall (atic VGI) F highly virulent ganisms (e.g. S. aureus, E. coli) one positive culture needed, f low-virulent ganisms (e.g. S. epidermidis) 2 me positive cultures are needed to confirm infection 2 2 blood cultures with the same pathogen obtained at different times Copyright: PRO-IMPLANT Foundation (N. Renz, A. Trampuz). 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.pro-implant-foundation.g

CLASSIFICATION Pathogenesis Peripheral VGI Intrathacic Atic VGI Intraabdominal perioperative Intra- postoperative contamination contiguous Soft tissue infection Mediastinitis Atoesophageal fistula Atoenteric fistula (duodenum > colon) Intraabdominal/pelvic abscess hematogeus Primary secondary bacteremia Clinical features Causative microganisms Acute: Acute pain, fever, rigs, prolonged wound discharge Chronic: graft occlusion with distal ischemia, septic emboli, pseudoaneurysm, anastomotic rupture with hemrhage Staphylococcus aureus, coagulasenegative staphylococci, gram-negative bacteria (Pseudomonas spp.) Fever, chills, heart failure, ( endocarditis-like ), chest pain, stroke/brain abscess (cerebral septic emboli), rupture with massive bleeding Staphylococcus aureus, coagulasenegative staphylococci, Cutibacterium (fmerly Propionibacterium) acnes, streptococci Abdominal pain, intermittent polymicrobial bacteremia (fecal fla, erosion of the intestine), gastrointestinal bleeding (hematemesis, hematochezia oder melaena), peripheral ischemia/emboli, palpable abdominal groin mass Gram-negative bacteria (Escherichia coli, Pseudomonas), enterococci, anaerobes (Bacteroides, Fusobacterium, anaerobic cocci), Candida The risk of hematogeus infection of VGI is highest in the early postoperative period (<2 months) and decreases over time because of partial endothelialization of the graft.

CLASSIFICATION accding to biofilm maturity Acute infection (immature biofilm) Pathogenesis Perioperative <8 weeks after surgery (early) Chronic infection (mature biofilm) 8 weeks after surgery (delayed, late) Hematogeus contiguous Surgical therapy Antimicrobial therapy DIAGNOSTIC WORK-UP <8 weeks of symptom duration Retention and debridement of graft possible (see management algithm) Biofilm-active (if available), consider suppressive treatment in difficult-totreat infections 8 weeks of symptom duration Partial complete excision/exchange of graft Biofilm-active (if available), consider suppressive treatment in difficult-to-treat infections and if complete exchange is feasible/possible All patients with suspected VGI infection: o C-reactive protein (CRP) and white blood cell count o Blood cultures (at least 3 sets) o Imaging : Peripheral VGI: ultrasound, computed tomographic angiography (CTA) Atic VGI: CTA (also in combination with positron-emission tomography, PET/CTA) MRI o Specific situations: o Preoperative setting: aspiration of perigraft fluid f culture, (avoid superficial swabs as they yield skin colonisation) o Intraoperative setting: perigraft tissue culture, sonication of retrieved synthetic graft, if removed o Atic VGI: test f occult blood in stool, consider endoscopy if atoenteric fistula suspected (sensitivity low, 55%) CT: sensitivity 85-00%, specificity 85-94%, MRI: sensitivity 68-85%, specificity 97-00%, PET: sensitivity 78-96%, specificity 70-93% (Wilson WR et al on behalf of the American Heart Association, Circulation 206) Note: many of the recommendations are based on expert opinion because rigous clinical data are t 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 vascular graft infections. F individual recommendations contact our Consultation Ptal at: cp.pro-implant-foundation.g

MANAGEMENT ALGORITHM PERIPHERAL VGI Local signs of infection Imaging (US/CT/PET-CT) Debridement, with graft retention, eradication Graft body involved? Anastomotic site involved? Bleeding/bacteremia? Extra-anatomic revascularization and graft excision (simultaneous staged procedure) Chronic infection difficult-to-treat infection*? Chronic infection difficult-to-treat infection*? Complete graft excision and reconstruction (in situ extraanatomic bypass), consider suppression Debridement, partial graft excision and reconstruction, eradication MANAGEMENT ALGORITHM AORTIC VGI* Diagstic wk-up (incl. blood cultures and imaging) Bacteremia/sepsis anastomotic disruption? Atoenteric fistula? Chronic infection difficult to treat-infection*? Complete graft excision Partial graft preservation retention with debridement * If the surgical treatment is less invasive than suggested by the algithm, consider long-term suppressive treatment to prevent relapse *Difficult-to-treat infections caused by pathogens resistant to biofilm-active antimicrobials: - Rifampin-resistant staphylococci - Ciprofloxacin-resistant gram-negative bacteria - Fungi (Candida spp.)

SURGICAL PROCEDURES FOR VGI INFECTIONS Peripheral VGI Debridement & retention 2weeks 0 weeks 2 weeks One-stage partial complete exchange/ reconstruction (in situ bypass) 2 weeks 0 weeks 2 weeks Extra-anatomic revascularization (in a ninfected field) followed by graft excision??? 4 weeks 4 weeks Atic VGI 2 weeks Retention of graft, partial complete exchange of graft 4-6 weeks 2 weeks (4-6 i.v., 6-8 p.o.) analogous to prosthetic valve endocarditis: 4-6 weeks f S. aureus, enterococci, gram-negative bacteria; 4 weeks f streptococci (2 weeks in combination with gentamicin in high susceptibility to penicillin) Debridement Explantation of implant Exchange of implant Reimplantation i.v. antibiotics al antibiotics with biofilm activity al antibiotics without biofilm activity Soft tissue management: The use of vascularized tissue flaps to provide coverage of infected grafts is beneficial in terms of sound dead space management, improved healing time, enhanced delivery of oygen, antimicrobials and phagocytes. Avoid long use of negative pressure wound therapy if graft in situ INDICATIONS FOR SUPPRESSIVE TREATMENT Difficult-to-treat infections and implant in infected area ( biofilm-active agent available) Remaining graft in case of chronic infection Relapsing infection

ANTIMICROBIAL TREATMENT Empirical intraveus treatment Peripheral VGI: Ampicillin/sulbactam 3x3g amoxicillin/clavulanic acid 3x2.2g + vancomycin 2x5mg/kg daptomycin x0mg/kg Atic VGI: Piperacillin/tazobactam 3-4x4.5g i.v. + vancomycin 2x5mg/kg daptomycin x0mg/kg if patient septic polymicrobial infection possible: add gentamicin x240mg i.v. if patient is allergic to penicillin: cefazolin 4x2 ( meropenem 3x2g, if anaphylaxis atic VGI) if fungal infection suspected: add caspofungin x70mg Targeted treatment f peripheral VGI Intraveus treatment (biofilm-active) (suppressive) Staphylococcus spp. Oxacillin-susceptible to penicillins methicillin-resistant Streptococcus spp. Penicillin-susceptible to penicillin 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 Rifampicin 2x450mg Cotrimoxazol 3x960mg Doxycyclin 2x00mg Doxycyclin 2x00mg Amoxicillin/clavulanic acid 3xg Enterococcus spp. Penicillin- and gentamicin (HL)- susceptible Amoxicillin 4x2g 3 ( gentamicin x3 mg/kg, if device in situ) to penicillins Vancomycin 2x5mg/kg Daptomycin x0mg/kg ( gentamicin x3 mg/kg, if device in situ) Enterobacteriaceae to penicillin Ceftriaxon x2g Piperacillin/tazobactam 3x4.5g Ciprofloxacin 3x400mg meropenem 3xg (if resistant to ciprofloxacin, consider long-term suppression)

Targeted treatment f atic VGI: Intraveus treatment after device removal (biofilm-active) (suppressive) Staphylococcus spp. Oxacillin-susceptible to penicillins methicillin-resistant Streptococcus spp. Penicillin-susceptible to penicillins Rifampicin 2x450mg p.o. - Flucloxacillin 6x2g - Cefazolin 3x2g - Vancomycin 2 2x5mg/kg - Daptomycin x 8-0mg/kg Gentamicin 2 x 3mg/kg - Penicillin G 4x5 Mio E - Amoxicillin 6x2g - Ceftriaxon x2g - Vancomycin 2 2x5mg/kg - Daptomycin x 8-0mg/kg Rifampicin 2x450mg Cotrimoxazol 3x960mg Doxycyclin 2x00mg Doxycyclin 2x00mg Amoxicillin/clavulanic acid 3xg Enterococcus spp. Penicillin- and gentamicin (HL)- susceptible Amoxicillin 6x2g 3 Gentamicin 2 x3mg/kg Penicillin- suscpetible and gentamicin (HL)- resistant (only E. faecalis) Amoxicillin 6x2g 3 Ceftriaxon 2x2g to penicillins enterococci Vancomycin 2 2x5mg/kg Daptomycin x0mg/kg - Gentamicin 2 x3mg/kg - Fosfomycin 3x5g Enterobacteriaceae to penicillins Candida spp. Ceftriaxon x2g Gentamicin 2 x3mg/kg Ciprofloxacin 3x400mg meropenem 3xg Amphotericin B (liposomal) x 3-5mg/kg Caspofungin x70 mg Anidulafungin x200 mg (if resistant to ciprofloxacin, consider long-term suppression) 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.