Transcript Antibiotic selection in the management of the Diabetic Foot

Antibiotic Selection in the
Management of the Diabetic Foot
Dr Jim Greig
Consultant Medical Microbiologist
24th June 2009
DDD per 1000 occupied patient bed days
Antimicrobial consumption PHNT Sep 071200
1000
WHO DDD
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PHNT Days
of therapy
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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
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 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
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
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
Others
Anaerobes
Pseudomonas
Coliforms
Group B
streptococcus
Enterococcus
S. aureus
(%)
Isolated bacteria (% of all bacteria isolated)
SIDESTEP study 2005
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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
N=31
Superficial wound swab
Deep ulcer wound aspirate
Bone biopsy (though
intact skin)
Culture positive
30 (97%)
18 (58%)
21 (68%)
Strains
2.5
1.3
1.4
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
Isolated bacteria (proportion of positive bone
biopsies) Senneville et al 2006
Others
Anaerobes
Pseudomonas
Coliforms
Group B
streptococcus
Enterococcus
CoNS
S. aureus
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40
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20
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Others
Anaerobes
Pseudomonas
Coliforms
Group B
streptococcus
Enterococcus
S. aureus
(%)
Isolated bacteria (% of all bacteria isolated)
SIDESTEP study 2005
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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
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
Commonly used antibiotics
Flucloxacillin
Pen V
Amoxil
Clindamycin
Co-amoxiclav
Levofloxacin
S. aureus and haemolytic streptococci
Avoid poor absorption, streps only
Streps and coliforms (if confirmed
sensitive)
Staphs and streps and anaerobes
Well absorbed and good tissue penetration
Staphs, streps, coliforms and anaerobes
good for soft tissues and bone Less
reliable oral bioavaliability
Similar to co-amoxiclav if combined
with clindamycin, well absorbed good
bone penetration
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
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 available
IDSA
Scottish Group
Pip/tazo (confident no MRSA)
Levofloxacin and clindamycin (confident no MRSA)
Meropenem or vancomycin, ceftazidime and metronidazole
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 treated
IDSA
Scottish Group
Flucloxacillin, clindamycin, cepahlexin, septrin, co-amoxiclav,
levofloxacin
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 coamoxiclav 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 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
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
Durations of treatment
Mild
5-7 days usually oral (high dose)
Moderate soft tissue
Osteomyelitis
Amputate
Viable infected bone
Retained residual bone
2-4 weeks initially IV usually
Stop within days
4-6 weeks route depends on drug
?? 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
MRSA bacteraemias Englans and Wales (Health
communities
Protection report 19th September 2008)
May be more virulent
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Treatment options are more
limited than an MSSA but
the M standards for methicillin not Multi!
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
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