Antibiotic Selection in the Management of the Diabetic Foot

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Antibiotic Selection in the Management of the
Diabetic Foot

• Dr Jim Greig
• Consultant Medical Microbiologist
• 24th June 2009

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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

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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

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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

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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

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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

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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

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• N31
• 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

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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

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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

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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

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Antibiotic associated diarrhoea

• Antibiotic associated diarrhoea
• 20-gt50 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

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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?

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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

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• 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

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• 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

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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

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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

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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)

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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!

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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

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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