Cochrane review Interventions for Impetigo

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Cochrane review- Interventions for Impetigo

• Sander Koning
• Koning S, Verhagen AP, van Suijlekom-Smit LWA,
  Morris A, Butler CC, van der Wouden JC. The
  Cochrane Library, Issue 2, 2003

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Desiderius Erasmus

• Painting by
• Hans Holbein,1523

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ImpetigoBackground

• Third most common skin disorder in children
• (after dermatitis/eczema and viral warts)
• 23 of children consult GP each year (UK, NL)
• Rising incidence
• Treatment mainly by GPs
• Causative agent S. aureus (S. pyogenes)
• Natural course?
• Complications?

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ImpetigoTreatment options

• (1) no treatment, waiting for natural resolution,
  hygiene measures
• (2) topical disinfectants
• (e.g. hexachlorophene, povidone-iodine,
  chlorhexidine)
• (3) topical antibiotics
• (e.g. neomycin, bacitracin, polymyxin B, fusidic
  acid, mupirocin)
• (4) systemic antibiotics
• (e.g. penicillin, (flu)cloxacillin,
  amoxicillin/clavulanic acid, erythromycin,
  cephalexin)
• Bacterial resistance in S. Aureus !

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Interventions for ImpetigoRationale for the
review

• Many options, guidelines vary widely
• Objectives
• To assess the effects of treatments for impetigo
• Types of studies
• Randomised trials
• Types of participants
• People with non-bullous or bullous, primary or
  secondary impetigo
• Types of interventions
• Any treatment, including antibiotics,
  disinfectants or any other intervention

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Interventions for impetigoSearch strategy

• Electronic search- Skin Group Specialised Trials
  Register (March 2002)- Cochrane Central
  Register of Controlled Trials (2002)- National
  Research Register (2002)- MEDLINE (1966
  to 2003)- EMBASE (1980 to 2000)- LILACS
  (2001) Handsearch- Yearbook of
  Dermatology (1938 - 1966)- Yearbook of Drug
  Therapy (1949 - 1966)Other- reference lists of
  articles- contacted pharmaceutical companies.

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Interventions for ImpetigoData collection
analysis

• Abstract reading and selection 2 independent
  reviewers
• Full copy reading and selection 2 independent
  reviewers
• Quality assessment 2 independent reviewers
• Data extraction 2 independent reviewers
• Primary Outcome (Odds Ratio for) cure after one
  week of treatment
• Meta-analysis (pooling) for comparisons that have
  been studied more than once

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Interventions for ImpetigoResults

• Studies identified (abstracts) approx. 700
• Full copies read 221
• Papers included 56 (57 RCTs)
• Total evaluable patients 3533
• Language of papers
• English 49
• Japanese 3
• Korean, Thai, Portuguese,
• Spanish and Danish 1 each

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Interventions for ImpetigoResults description
of the 57 included studies

• 38 different treatments studied
• 20 oral, and 18 local treatments
• Studies comparing
• Two different oral antibiotics 25
• (Cephalosporines 16)
• (Macrolides (erythrom. or azithrom.) 10)
• A topical vs an oral antibiotic 22
• (Erythromycin, mupirocin, or both 19)
• Antiseptic or disinfecting treatments 2
• Placebo-controlled trials 5

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RESULTSComparisonTopical antibiotic vs
placebo(5 studies)

• No studies OR (95 CI)
• Mupirocin 3 5.40 (2.79 - 10.45)
• Fusidic acid 1 8.65 (3.88 - 19.29)
• Bacitracin 1 3.97 (0.15 to 104.18)
• Overall 5 6.49 (3.93 - 10.73).

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ComparisonTopical antibiotic versus placebo
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Comparison Topical vs another topical
antibiotic (12 studies)

• No studies OR (95 CI)
• Fusidic acid with mupirocin 4 1.22 (0.69 to
  2.16)
• All other comparisons were only represented by a
  single small study without a siginificant
  difference in results

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Comparison Topical versus another topical
antibiotic
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Comparison Topical versus oral antibiotic (16
studies)

• no studies OR (95 CI)
• Mupirocin versus
• Erythromycin 10 1.76 (1.05 to 2.97 )
• Dicloxacillin 1 NS
• Cephalexin 1 NS
• Ampicillin 1 NS
• Fusidic acid versus
• Erythromycin 1 8.38 (1.77 39.69)
• Cefuroxim 1 NS

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Comparison Topical versus oral antibiotic (16
studies)

• Mupirocin versus erythromycin, (sensitivity
  analysis for quality), dicloxacillin

16
Comparison Topical antibiotic versus antiseptic
(2 studies)

• Study OR (95 CI)
• Bacitracin vs hexachlorophene 3.97 (0.15 to
  104.18)
• fusidic acid vs hydrogen peroxide 1.79 (0.99
  to 3.25).

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Comparison Oral versus other oral antibiotic
(22 studies)

• cephalosporin vs another antibiotic (7 studies)
• no differences
• one cephalosporin vs another cephalosporin (4
  studies)
• no differences
• macrolide vs penicillin (6 studies)
• Erythromycin superior to penicillin
• macrolide vs another macrolide (1 study)
• no difference
• penicillin vs other oral antibiotics (4 studies)
• Amoxicillinclavulanic acid superior to
  amoxicillin alone
• Cloxacillin superior to penicillin

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Interventions for impetigoDiscussion

• Many small trials of various quality with
  inconclusive results.
• Some large trials of good quality.
• Few placebo-controlled trials.
• Antiseptic treatment inadequately studied.

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Interventions for impetigoConclusions and
Implications for Practice

• No evidence for the value of disinfecting
  measures
• Topical antibiotics
• Good evidence that topical mupirocin and fusidic
  acid are equal to or possibly more effective than
  oral treatment for people with limited disease.
  Other topical antibiotics seem less effective.
• Oral antibiotics
• No evidence that penicillin is effective. No
  clear preference for B-lactamase resistant
  penicillins (cloxacillin, dicloxacillin and
  flucloxacillin), broad spectrum penicillins
  (ampicillin, amoxicillin plus clavulanic acid),
  cephalosporins, and macrolides.

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Interventions for impetigo Considerations for
treatment

• Actual presence of bacterial resistance in the
  region and specific patient population (for
  erythromycin, fusidic acid, any antibiotic)
• Other criteria can be decisive
• - price
• - (unnecessary) broadness of spectrum
• - wish to save a particular antibiotic for a
  specific goal
• (eradication of MRSA, treatment of severe bone
  infections)

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Interventions for impetigoImplications for
Research

• Trials should
• - compare treatments for a specific disease,
  rather than the effectiveness of a specific
  antibiotic on a variety of (skin) infections
• - use objective outcome measures, instead of
  subjective judgements such as 'improved',
  'satisfactory.
• Unknown territory
• - mechanisms of bacterial resistance induction
• - new antibiotics
• - efficacy of disinfecting treatments
• - natural course of impetigo