Diabetic foot infection diagnosis and treatment workshop

Transcription

1 Diabetic foot infection diagnosis and treatment workshop Nashwan Al Naiemi Medical Microbiologist, ZGT, Almelo Edgar J.G. Peters Internist, VU Univ Med Cent, Amsterdam Subjects Introduction / case Diagnosis Infection Osteomyelitis Pathogens Treatment (what, how and how long) Credits to Prof. Schaper, Maastricht MUMC+ Mr H, 60 years: infection? Epidemiology foot infections in diabetes Past: DM2, neuropathy, BDP Present: 4 months skin defect tip hallux after infected toe. Used penicillin for 10 days. Gets tired legs easily Med: Glimepiride / metformin / AB Exam: Crusta tip hallux, some hyperaemia and swelling, no palpable periph puls. Lab: Hba1c 63 mmol/mol (7.9%), CP 5 mg/l, Leuco 5,8 x 109/L, Creat 130 ug/l Incidence / prevalence: isk: 4 % lifetime - 9% in 3 years 50% of foot ulcers infected at presentation 18% osteomyelitis at presentation of ulcer in Eurodiale study Amputation: 60% 2 nd to infected ulcer Expensive If osteomyelitis: amputation in 69% of cases (= O 16) Verhoeven 1991; Armstrong 2002; Pecoraro 1991; McMahon 1995; Lavery 2006; Prompers 2008; Eurodiale data Diabetic foot ulcer classification P Perfusion E Extent D Depth I Infection S Sensibility IWDGF/ IDSA classification Grade 1: no signs or symptoms Grade 2: mild 2 signs of local inflammation, erythema 2 cm Grade 3: moderate erythema 2 cm, lymphangitis, deeper than skin: abscess, arthritis, osteomyelitis Grade 4: severe SIS: systemic toxicity or metabolic decompensation Schaper 2004 Schaper 2004, Lipsky 2004, Lipsky 2012

2 IWDGF/IDSA classification predicts outcome Diagnosis of infection 1666 patients in a prospective study 90% 80% Hospitalisation p < % Amputation p < % Infection = clinical diagnosis Symptoms and signs often mild despite serious infection 70% 60% 54% Limited usefulness of laboratory variables: 50% 40% 46% 50% of inflammatory parameters normal in foot abscess 30% 20% Chronic wound become colonised: 10% 0% 10% 6% None Mild Moderate Severe No infection Mild Moderate Severe 3% 3% None infection Mild Moderate Severe cultures not useful for diagnosis Lavery, Clin Infect Dis, 2007 Lipsky 2004, Peters 2012 Your antibiotic advice? Clindamycin Flucloxacillin Ciprofloxacin Clindamycin and ciprofloxacin Meropenem S. aureus clinda, fluclox S, cipro, rif S, cotrim S Coag. Neg. Staphylococcus clinda, fluclox, cipro S, rif, cotrim S E. cloacae cipro S, cotrim, mero S E. coli cipro S, cotrim, mero S Mr H: osteomyelitis? Exam: Crusta tip hallux, erythema and edema hallux, absent pulsations Lab: Hba1c 63, CP 5, Leuco 5,8, Creat 130 What next? emoval of crusta: some yellow debris, deep defect. Probe-to-bone test: + Clinical clues for osteomyelitis Accuracy of tests for osteomyelitis Deep and large ulcers Chronic ulcers "Sausage toe" Visible bone Palpable bone Leukocytosis Elevated ES/CP Clinical impression Likelihood ratio negative (L-): 0.54 Likelihood ratio positive (L+): 5.5 Berendt 2008; Butalia 2008; Dinh 2008

3 Probe to bone Mr H: yes / no osteomyelitis? Neg predictive value up to 98% Positive L: Negative L: 0.15 tot 0.68 Exam: Crusta tip hallux, erythema and edema hallux, absent pulsations. emoval of crusta: some yellow debris, deep skin defect. Probe-to-bone test: + Lab: Hba1c 63, CP 5, Leuco 5,8, Creat 130 What next? X-foot: bone destruction Grayson 1995,Shone 2006, Lavery 2007 Plain radiography (in DFO) MI (in DFO) Summary positive L 2.3 Summary negative L 0.63 Diagnostic O 2.84 Sensitivity 28% to 75% Only marginally predictive if positive Negative result even less predictive No studies to follow up X-rays Objectives Microbiology Pathogenesis Principles Specials Conclusions Summary positive L 3.8 Summary negative L 0.14 Diagnostic O of 42 (CI, ) Sensitivity 77% to 100% Specificity 40% to 100% Objectives Microbiology Pathogenesis Principles Specials Conclusions Lavery Peters Bush, High risk diabetic foot, New York, 2010 Lavery Peters Bush, High risk diabetic foot, New York, 2010 Xray of mr H Mr H: yes / no osteomyelitis? Exam: Crusta tip hallux, erythema and edema hallux, absent pulsations. emoval of crusta: some yellow debris, deep skin defect. Probe-to-bone test: + Lab: Hba1c 63, CP 5, Leuco 5,8, Creat 130 X-foot: bone destruction What next? Bone biopsy: Path: histological evidence of infection Culture: S. aureus and E. coli

4 Bot biopsy Gold standard in osteomyelitis Comparison of culture results 1. Pathology 2. Microbiology Senneville, Clin Infect Dis 2006 Culture method Culture results Superficial swab Deep swab Tissue biopsy Number of bacteria per sample MDO De Sotto, Diabetologia 2010 De Sotto, Diabetologia 2010 Outcome with bone biopsy Bacterial culture the GOLD STANDAD? Senneville CID 2008

5 Bacterial culture the GOLD STANDAD? easons of undiagnosed clinical sample EXAMPLES OF LOW-LEVEL MUTATIONS IN TUMO CLINICAL SAMPLES, PEVIOUSLY INVISIBLE VIA SANGE SEQUENCING, THAT BECOME DETECTABLE VIA COLD PC Sanger-di-deoxy-sequencing of CLINICAL tumor samples for p53 exon 8 mutations EGULA PC (94 o C denaturation) 167 bp p53 exon 8 sequence COLD PC (denaturation at Tc=86.5 o C) Focussing on the wrong sample Detection of non viable bacteria because of antibiotic treatment Inappropiate transport conditions; not strictly anaerobic Lung tumor 64 reverse seq. NO mutation visible forward seq. NO mutation visible Lung tumor 64 reverse seq. G>A mutation VISIBLE INDEPENDENT VEIFI CATION via FLP G>A mutation verified 26 Sequencing Two different genes Naiemi, JCM 2006 Next Generation Sequencing (NGS) Next Generation Sequencing (NGS) 16S PC of patient X gave a strong signal in real-time 16S PC. The bacterial population of a pus sample has been determined with deep sequencing (NGS). species percentage Fusobacterium nucleatum 67 Prevotella species 22 Filifactor alocis 3 Dialister invisus 3 Bacteroides species 2 Campylobacter gracilis 2 Porphyromonas endodontalis 0.5

6 Microbiology Most diabetic foot infections are polymicrobial, with up to five to seven different specific organisms Superficial diabetic foot infections are likely due to aerobic gram-positive cocci (including S. aureus, S. agalactiae, S. pyogenes, and coagulase-negative staphylococci). Ulcers that are deep, chronically infected, and/or previously treated with antibiotics are more likely to be polymicrobial, above organisms in addition to enterococci, Enterobacteriaceae, Pseudomonas aeruginosa, and anaerobes. Wounds with extensive local inflammation, necrosis, gangrene should be presumed to have anaerobic organisms in addition to the above pathogens, include anaerobic streptococci, Bacteroides species, and Clostridium species E. coli (ESBL) amoxicilline augmentin S cefazolin cefuroxim cefotaxime ceftazidime Piperacilline/tazobactam S/ imipenem S meropenem S trimetroprim/sul S/ ciprofloxacin S/ gentamincine S/ ESBLs in The Netherlands Community aquired ESBLs in The Netherlands is 3%-8,6% Prevalance of ESBLs in The Netherlands is 5,5% Paltansing, EID 2013; euland, ECCMID 2013; Carbapenemase positive Occurrence of carbapenemase-producing Enterobacteriaceae in 38 European countries K. pneumoniae amoxicilline augmentin Piperacilline/tazobactam cefazolin cefuroxim cefotaxime ceftazidime cefepime imipenem meropenem trimetroprim/sul ciprofloxacin gentamincine colistin tigecycline S/ S/ S/ S/ S/

7 Microbiologie Microbiology Zijn alle diabetische voet infecties polymicrobieel?. Waarschijnlijk niet! Staphylococcus aureus ß-haemolytic streptococci Aerobic Gram-negative rods, e.g. E. coli Linezolid vs ampicillin/sulbactam trial: geen verschil in cure rates Coagulase-negative staphylococci Other organisms Lipsky, CID, 2004 Treatment Wat is uw locale resistentie? S. aureus MUMC+ op n % sens Flucloxacilline % Clindamycine % Ciprofloxacine % A Oude Lasthof What is your local resistance pattern? UMC Utrecht diabetic foot infection n=110 n % sens S. aureus 44 Flucloxacillin 100% Clindamycin 83% Systematic review antibiotische behandeling 29 trials 12 studies over antibiotica 7 in osteomyelitis 1 bone biopsie versus empirische therapie 2 vroege chirurgische interventie Gram negative rods 29 Ciprofloxacin 78%

8 esults systematic review IWGDF No differences among antibiotic regimes Bone biopsy + rifampicine (retrosp trial): better outcome Early surgery: decrease in major amputation (2 retrosp studies) Healing percentages Soft tissue 48-90% Soft tissue and osteomyelitis 61-94% Osteomyelitis treated conservatively with 3-6 months of antibiotics: 65-80% Peters DMM 2012 Antibiotics: how and how long? Infection severity oute Duration Class 2: mild Class 3: moderate / severe oral oral/initially iv 1-2 weeks 2-4 weeks Bone/joint: esected Debrided (soft tissue infection) No surgery or dead bone oral/initially iv oral/initially iv oral/initially iv 2-5 days 4-6 weeks > 3 months Which antibiotic? Which antibiotic? Which antibiotic? IDSA guidelines 2012 Infectie severity Oral Spectrum Flucloxacillin Mild (2) + Gram + Clindamycin Mild (2) + Gram + Cephalexin Mild (2) + Gram + Amox/clav Severe (3+4) + Gram + / - Pip/tazo Severe (3+4) - Gram + / - Moxifloxacin Severe (3+4) + Gram + / - Cipro/clinda Severe (3+4) + Gram + / - IDSA 2012 Clin Infect Dis May 2012

9 Soort infectie/wonden Klinisch niet geïnfecteerd Milde infectie: oppervlakkige infecties met beperkte cellulitis (<2cm erytheem) Matig-ernstige infectie: uitgebreide infecties zonder septische shock Ernstige infecties met septische shock of hoog risico op ESBL Osteomyelitis Empirisch gericht op Geen behandeling S. aureus en streptokokken Gram-positieve kokken, Gramnegatieve staven, anaeroben Gram-positieve kokken, Gramnegatieve staven, anaeroben, pseudomonad en Zoals bij matige ernstige infectie Empirische antibiotica 1 e keus Flucloxacilline of cefalexine Amoxicilline/clavulaanzuur of 2 e /3 e generatie cefalosporine, eventueel gecombineerd met anaerobe dekking (clindamycine of metronidazol) Onbekend / Pseudomonas: zoals bij matig-ernstige infectie + gentamicine of chinolon ESBL: imipenem/cilastatine meropenem Zoals bij matige ernstige infectie Empirische antibiotica 2 e keus Toedienings Vorm Duur behandeling Clindamycine * Oraal 1-2 weken Clndamycine + chinolon* Onbekend/pse udomonas: Imipenem/cilas tine Meropenem ESBL: Ertapenem (indien pseudomonas uitgesloten) Intraveneus **. Per os bij goede absorptie uit de tractus digestivus (chinolonen, clindamycine) Intraveneus** Intraveneus. Per os bij goede absorptie uit de tractus digestivus (chinolonen, clindamycine 2-4 weken 2-4 weken Na adequate amputatie: 2-5 dagen Na operatie alleen infectie van weke delen: 2-4 weken Na operatie nog infectie van restant vitaal bot: 4-6 weken Geen operatie of na operatie nog dood bot aanwezig: >3 maanden Ciprofloxacin Exposure to ciprofloxacin during the previous 30 days was an independent predictor of resistance to ceftazidime, imipenem, meropenem, piperacillin tazobactam and ciprofloxacin (p<0.001) (López-Dupla et al., 2009) Lipman et al. (1998) suggest that to achieve adequate serum ciprofloxacin levels in severe sepsis, 400 mg i.v. 8-hourly should be used in adults Time = tissue Step 1 Debridement (at bedside or in O) to: Confirm diagnosis Drainage of pus / decompression of compartments emoval of dead tissue, including bone Material for Gram stain / culture Start empirical antibiotic therapy Assess vascular status Improve metabolic condition Time = tissue Step 2 (72 hours) Step days Adjust antibiotics epeat debridement? Start intensive wound care (e.g. VAC) Angiography followed by revascularisation? Antibiotics: stop or oral? epeat debridement? econstructive foot surgery? Offloading

10 Developments in case Mr H. Admitted for 1 week Amoxicillin/clavulate 1,25 g iv qid Toe pressure 28 mmhg, tcpo 2 22 mmhg MA: all crural vessels obstructed Endovascular procedure: proper flow to the forefoot Distal toe amputation with planning of foot reconstruction