Interventions for impetigo Edited (no change to conclusions)

Abstract

Abstract Background

Impetigo is a common, superficial bacterial skin infection, which is most frequently encountered in children. There is no generally agreed standard therapy, and guidelines for treatment differ widely. Treatment options include many different oral and topical antibiotics as well as disinfectants. This is an updated version of the original review published in 2003.

Objectives

To assess the effects of treatments for impetigo, including non‐pharmacological interventions and 'waiting for natural resolution'.

Search methods

We updated our searches of the following databases to July 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched online trials registries for ongoing trials, and we handsearched the reference lists of new studies found in the updated search.

Selection criteria

Randomised controlled trials of treatments for non‐bullous, bullous, primary, and secondary impetigo.

Data collection and analysis

Two independent authors undertook all steps in data collection. We performed quality assessments and data collection in two separate stages.

Main results

We included 57 trials in the first version of this review. For this update 1 of those trials was excluded and 12 new trials were added. The total number of included trials was, thus, 68, with 5578 participants, reporting on 50 different treatments, including placebo. Most trials were in primary impetigo or did not specify this.

For many of the items that were assessed for risk of bias, most studies did not provide enough information. Fifteen studies reported blinding of participants and outcome assessors.

Topical antibiotic treatment showed better cure rates than placebo (pooled risk ratio (RR) 2. 24, 95% confidence interval (CI) 1.61 to 3.13) in 6 studies with 575 participants. In 4 studies with 440 participants, there was no clear evidence that either of the most commonly studied topical antibiotics (mupirocin and fusidic acid) was more effective than the other (RR 1.03, 95% CI 0.95 to 1.11).

In 10 studies with 581 participants, topical mupirocin was shown to be slightly superior to oral erythromycin (pooled RR 1.07, 95% CI 1.01 to 1.13). There were no significant differences in cure rates from treatment with topical versus other oral antibiotics. There were, however, differences in the outcome from treatment with different oral antibiotics: penicillin was inferior to erythromycin, in 2 studies with 79 participants (pooled RR 1.29, 95% CI 1.07 to 1.56), and cloxacillin, in 2 studies with 166 participants (pooled RR 1.59, 95% CI 1.21 to 2.08).

There was a lack of evidence for the benefit of using disinfectant solutions. When 2 studies with 292 participants were pooled, topical antibiotics were significantly better than disinfecting treatments (RR 1.15, 95% CI 1.01 to 1.32).

The reported number of side‐effects was low, and most of these were mild. Side‐effects were more common for oral antibiotic treatment compared to topical treatment. Gastrointestinal effects accounted for most of the difference.

Worldwide, bacteria causing impetigo show growing resistance rates for commonly used antibiotics. For a newly developed topical treatment, retapamulin, no resistance has yet been reported.

Authors' conclusions

There is good evidence that topical mupirocin and topical fusidic acid are equally, or more, effective than oral treatment. Due to the lack of studies in people with extensive impetigo, it is unclear if oral antibiotics are superior to topical antibiotics in this group. Fusidic acid and mupirocin are of similar efficacy. Penicillin was not as effective as most other antibiotics. There is a lack of evidence to support disinfection measures to manage impetigo.

Author(s)

Sander Koning, Renske van der Sande, Arianne P Verhagen, Lisette WA van Suijlekom‐Smit, Andrew D Morris, Christopher C Butler, Marjolein Berger, Johannes C van der Wouden

Abstract

Plain language summary

Interventions for the skin infection impetigo

Impetigo causes blister‐like sores. The sores can fill with pus and form scabs, and scratching can spread the infection. Impetigo is caused by bacteria. It is contagious and usually occurs in children. It is the most common bacterial skin infection presented by children to primary care physicians. Treatment options include topical antibiotics (antibiotic creams), oral antibiotics (antibiotics taken by mouth), and disinfectant solutions. There is no generally agreed standard treatment, and the evidence on what intervention works best is not clear.

We identified 68 randomised controlled trials comparing various treatments for impetigo. Altogether, these studies evaluated 26 oral treatments and 24 topical treatments, including placebo, and results were described for 5708 participants.

Overall, topical antibiotics showed better cure rates than topical placebo.

Two antibiotic creams, mupirocin and fusidic acid, are at least as effective as oral antibiotics where the disease is not extensive. There was no clear evidence that either of these most commonly studied topical antibiotics was more effective than the other.

Topical mupirocin was superior to the oral antibiotic, oral erythromycin.

We found that the oral antibiotic, oral penicillin, is not effective for impetigo, while other oral antibiotics (e.g. erythromycin and cloxacillin) can help.

It is unclear if oral antibiotics are superior to topical antibiotics for people with extensive impetigo.

There is a lack of evidence to suggest that using disinfectant solutions improves impetigo. When 2 studies with 292 participants were pooled, topical antibiotics were significantly better than disinfecting treatments.

Reported side‐effects for topical treatments were mild and low in frequency; the treatments sometimes resulted in itching, burning, or staining. Oral antibiotics produced gastrointestinal complaints, such as nausea and diarrhoea, in 2% to 30% of participants, depending upon the specific antibiotic.

Worldwide, bacteria causing impetigo show growing resistance rates for commonly used antibiotics. For a newly developed topical treatment, retapamulin, no resistance has yet been reported.

Author(s)

Sander Koning, Renske van der Sande, Arianne P Verhagen, Lisette WA van Suijlekom‐Smit, Andrew D Morris, Christopher C Butler, Marjolein Berger, Johannes C van der Wouden

Reviewer's Conclusions

Authors' conclusions

Implications for practice Implications for topical disinfectants in clinical practice

There is a lack of evidence from RCTs for the value of disinfecting measures in the treatment of impetigo, as a sole or supplementary treatment.

Implications for topical antibiotics in clinical practice

There is good evidence that the topical antibiotics mupirocin and fusidic acid are equal to, or possibly more effective than, oral treatment for people with limited disease. Fusidic acid, mupirocin, and retapamulin are probably equally effective; other topical antibiotics seem less effective. In general, oral antibiotics have more side‐effects than topical antibiotics, especially gastrointestinal side‐effects.

Implications for use of systemic antibiotics in clinical practice

What is stated in the previous paragraph regarding the comparison with topical antibiotics is equally relevant here. The only oral antibiotic that has been compared to placebo is penicillin, and this was in an old study (Ruby 1973): no difference was found, and the confidence interval was large. Based on the available evidence on efficacy, no clear preference can be given for B‐lactamase resistant narrow‐spectrum penicillins such as cloxacillin, dicloxacillin and flucloxacillin, or for broad spectrum penicillins such as ampicillin, amoxicillin with clavulanic acid, cephalosporins or macrolides.

General considerations regarding the choice of antibiotics

Other criteria, such as price, (unnecessary) broadness of spectrum, and wish to reserve a particular antibiotic for specific conditions, can be decisive. Resistance rates against erythromycin seem to be rising. In general, oral antibiotics have more side‐effects, especially gastrointestinal ones. There is insufficient evidence to say whether oral antibiotics are better than topicals for more serious and extensive forms of impetigo. From a practical standpoint, oral antibiotics might be an easier option for people with very extensive impetigo.

Implications for research

Trials should be powered to compare treatments for a specific disease entity, rather than the effectiveness of a specific antibiotic on a variety of (skin) infections, as treatment may impact differently on separate subtypes of skin and soft tissue infections. As seen in this review, trials that study one treatment for several diseases often show inconclusive results for specific diagnoses. Future research on impetigo should make a careful power calculation as most included studies included too few participants with impetigo to meaningfully assess differences in treatment effect.

Establishing the natural course of impetigo without any form of antibiotic treatment would be useful. However, although impetigo can be considered a minor ailment, studies with a non‐intervention arm seem ethically impracticable. Comparator treatments may include the best identified options for non‐antibiotic management.

The relative absence of data on the efficacy of topical disinfectants is a research gap that needs to be filled. These agents may not contribute to antibiotic resistance, and they are cheap. This research may be of particular importance for developing countries.

Preferably, a trial on impetigo should:

  • not include participants with a variety of skin diseases and soft tissue infections. If it does, results should be presented separately by diagnosis;
  • focus on either bullous or non‐bullous impetigo and on either primary or secondary impetigo;
  • report resistance rates of causative bacteria against the studied antibiotic and against reference antibiotics such as erythromycin, mupirocin and/or fusidic acid, at baseline and at follow‐up;
  • use clear and objective outcome measures for cure and improvement of impetigo, instead of subjective judgements such as 'improved', 'satisfactory', and 'good response'. Key elements defining clinical cure could be absence of crusts, dryness, intactness, and absence of redness of skin. A parameter of improvement could be 'size of affected surface'. Choosing 'standard' follow‐up periods, e.g. 7, 14, or 21 days, will facilitate the comparison of studies; and
  • include a placebo group, or at least a 'gold standard' reference group. For topical treatments, mupirocin or fusidic acid could be considered 'gold standard'.

As part of the issue of antibiotic resistance, impetigo studies that establish the contribution of the studied treatment to the development of bacterial resistance are desirable.

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