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 sepsisRetain useful functioning limbPrevent the induction and proliferation of antimicrobial resistanceAvoid drug side effects and antibiotic associated diarrhoeaAffordable costs ie cheap

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

Typical infecting pathogensCellulitis on intact skin S.aureus, haemolytic streptococci (A,B,C,G)

Infected ulcerEarly ‘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

Colonising bacteriaNo 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

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

Isolated bacteria (% of all bacteria isolated) SIDESTEP study 2005

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Sampling of the woundsSuperficial 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

N=31Culture 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 pathogensRef: Clin Infect Dis 2009; 48: 888-893

Other studies have put the concordance consistently below 50%

Isolated bacteria (proportion of positive bone biopsies) Senneville et al 2006

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Determining the severity of the infectionApplication of simple clasification allows one to select the narrowest spectrum antibiotics

Degree of tissue involvement

Extent of exposure to MDR flora

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 infectionInvolvement of deep tissues/stable patient/MODERATE

local inflammation with spreading cellullits/ lymphangitis or spread deep to the fascia/abscessOsteomyelitis/MODERATE

Involvement of deep contiguous bony structuresDiabetic foot infection leading to systemic toxicity/SEVERE

Commonly used antibioticsFlucloxacillin 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 anaerobesgood for soft tissues and bone Less reliable oral bioavaliability

Levofloxacin Similar to co-amoxiclav if combined with clindamycin, well absorbed good bone penetration

Antibiotic associated diarrhoeaAntibiotic 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

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?

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 availableIDSA 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

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 treatedIDSA Flucloxacillin, clindamycin, cepahlexin, septrin, co-amoxiclav,

levofloxacin

Scottish Group Flucloxacillin, doxycycline, clindamycin

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

Treatment of OsteomyelitisUp to 80% of osteomyelitis can be treated medically providing:Get the right pathogenGet the right antibiotic at the right dose and the right routeGet 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

Treatment of Osteomyelitis

Bone infections are problematic because:Need protracted treatment courses with problems of side effects and complianceFewer objective signs of resolutionSpectre of amputation awaiting those who fail treatmentGreater 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

Durations of treatmentMild 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)

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!

MRSA bacteraemias Englans and Wales (Health Protection report 19th September 2008)

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MRSAIs 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

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