Antibiotic Selection in the Management of the Diabetic Foot

1. Antibiotic Selection in the Management of the Diabetic Foot Dr Jim Greig Consultant Medical Microbiologist 24th June 2009

3. What do we want from antibiotics? Prevent systemic sepsis Retain useful functioning limb Prevent the induction and proliferation of antimicrobial resistance Avoid drug side effects and antibiotic associated diarrhoea Affordable costs ie cheap

4. Initial management of the infected foot Assess extent of the infection Probe the base of the ulcer looking for collections and sinus tracts Can the bone can be painlessly probed Toilet and debride the wound, tissues and bone biopsies preferable to swabs Transport the samples to the laboratory in a timely manner, anaerobes are fragile

5. Typical infecting pathogens Cellulitis on intact skin S.aureus, haemolytic streptococci (A,B,C,G) Infected ulcer Early ‘antibiotic naïve’ S.aureus, haemolytic streptococci (A,B,C,G) Late ‘antibiotic experienced’ Staphs, streps, coliforms, pseudomonas and diphtheroids Fetid gangrenous As above and anaerobes

6. Colonising bacteria No ulcer bed is sterile (nor do you want it to be) Antibiotic exposure creates an ecological niche for MDR bacteria Status of enterococci, pseudomonas, CoNS etc very difficult to asses Target the main pathogens and see If antibiotic experienced or treatment fails consider better sampling or broader spectrum

7. Infecting flora of ulcer wounds Typically in pre treated complex ulcers on average 3-5 bacteria will be isolated Only a minority of bacteria isolated from polymicrobial wounds are identifiable by standard techniques and this is likely to be the same with diabetic foot infections Need for better microbiological studies into the infecting flora

9. Sampling of the wounds Superficial samples yield more strains of bacteria and correlate poorly with deeper specimens though needle aspirates of soft tissue samples have a greater diagnostic precision Bone biopsies are the gold standard for osteomyelitis The correlation with superficial samples is poor, both for sensitivity and specificity Suggested that there are better clinical outcomes when treatment is directed by bone biopsy

10. N=31 Culture positive Strains Superficial wound swab 30 (97%) 2.5 Deep ulcer wound aspirate 18 (58%) 1.3 Bone biopsy (though 21 (68%) 1.4 intact skin) Using bone biopsy as the gold standard the sensitivity and specificity of superficial wound cultures was 85% and 0%! Superficial wounds may be used to exclude MDR pathogens but cannot be used to definitively identify the likely pathogens Ref: Clin Infect Dis 2009; 48: 888-893 Other studies have put the concordance consistently below 50%

13. Determining the severity of the infection Application of simple clasification allows one to select the narrowest spectrum antibiotics Degree of tissue involvement Extent of exposure to MDR flora

14. Infectious Diseases Society of America classification Involvement of skin and soft tissue only/MILD Wound inflammation, cellulitis or erythema do not extend beyond 2cm, no systemic manifestations of infection Involvement of deep tissues/stable patient/MODERATE local inflammation with spreading cellullits/ lymphangitis or spread deep to the fascia/abscess Osteomyelitis/MODERATE Involvement of deep contiguous bony structures Diabetic foot infection leading to systemic toxicity/SEVERE

15. Commonly used antibiotics Flucloxacillin S. aureus and haemolytic streptococci Pen V Avoid poor absorption, streps only Amoxil Streps and coliforms (if confirmed sensitive) Clindamycin Staphs and streps and anaerobes Well absorbed and good tissue penetration Co-amoxiclav Staphs, streps, coliforms and anaerobes good for soft tissues and bone Less reliable oral bioavaliability Levofloxacin Similar to co-amoxiclav if combined with clindamycin, well absorbed good bone penetration

16. Antibiotic associated diarrhoea Antibiotic associated diarrhoea 20->50% of AAD due to Clostridium difficile 2-10% of community diarrhoea due to C. difficile often with no recent hospitalisation Usually a mild nuisance disease but can be fatal Antibiotics to worry about: Clindamycin Cephalosporins esp 2/3 gen Quinolones Co-amoxiclav

17. Principles of antibiotic choice Likely infecting flora, depends to a great degree on how extensive the infection is, duration or the infection and previous exposure to antibiotics Route of the antibiotic and likely drug penetration What is the local resistance flora Where are you going to go when it is time for orals?

18. Antibiotic selections Life threatening sepsis Vancomycin (or other MRSA agent), Pip/Tazo and 1-3 days of gentamicin (step down therapy) Little time to play with Broad spectrum of likely pathogens MRSA and MDR coliforms possible Use step down therapy when cultures available IDSA Pip/tazo (confident no MRSA) Levofloxacin and clindamycin (confident no MRSA) Meropenem or vancomycin, ceftazidime and metronidazole Scottish Group Pip/tazo and vanc or ciprofloxacin and metronidazole

19. Mild (superficial wound infection) Vast majority of pathogens gram positive Assess if MRSA likely or previously confirmed Flucloxacillin (at least 500mg QDS) or clarithromycin (at least 500mg BD) The laboratory can turn a result around in 24-48 hours Treat until resolved and if not resolved in 5-7 days review what is being treated IDSA Flucloxacillin, clindamycin, cepahlexin, septrin, co-amoxiclav, levofloxacin Scottish Group Flucloxacillin, doxycycline, clindamycin

20. Moderate disease (not involving bone) The urgency of the correct choice increases The bacteriological causes for the infection may broaden but the majority are still gram positive Can I await Micro confirmation, can I use a step down approach? Empirical option if treatment needed straight away is co-amoxiclav or levofloxacin and clindamycin in the penicillin allergic IDSA Co-amoxiclav, septrin, levofloxacin and metronidazole Scottish Group In antibiotic naïve treat for S aureus, if experienced co-amoxiclav, ciprofloxacin and metronidazole, gentamicin and metronidazole, ciprofloxacin and clindamycin

21. Treatment of Osteomyelitis Up to 80% of osteomyelitis can be treated medically providing: Get the right pathogen Get the right antibiotic at the right dose and the right route Get the duration right Antibiotics are delayed in reaching site of infection due to need for new tissue growth Need to treat for 4-6 weeks to accommodate for this If site is removed then can effectively stop treatment if all infected tissues removed

22. Treatment of Osteomyelitis Bone infections are problematic because: Need protracted treatment courses with problems of side effects and compliance Fewer objective signs of resolution Spectre of amputation awaiting those who fail treatment Greater need to use antibiotics one is confident of success with from initiation Options I favour are IV co-amoxiclav with preferred oral switch to quinolone and clindamycin

23. Durations of treatment Mild 5-7 days usually oral (high dose) Moderate soft tissue 2-4 weeks initially IV usually Osteomyelitis Amputate Stop within days Viable infected bone 4-6 weeks route depends on drug Retained residual bone ?? Greater than 3 months (IDSA REC)

24. MRSA What is so special about MRSA? Intrinsically resistant to commonly used antibiotics Ability to spread rapidly through hospitalised communities May be more virulent Treatment options are more limited than an MSSA but the M standards for methicillin not Multi!

25. MRSA Is one adding the antibiotic or substituting? Vancomycin and oral rifampicin Clindamycin if strain known sensitive (40%) Oral doxycycline and rifampicin Other options include, linezolid, daptomycin, trimethoprim In most cases the above antibiotics are a substitution for flucloxacillin/clarithromycin in mild disease and and addition in moderate and severe disease

26. Summary of Options Numerically speaking there are numerous options In reality the nature of the infections and host attributes is stacked against you from the outset Prudent use of antibiotics and sensible use of the laboratory will assist you in management Antibiotic associated side effects are becoming more important and effective use of oral antibiotics will decrease hospitalisation