Interventions of Impetigo

Interventions for impetigo (Review)
Koning S, Verhagen AP, van Suijlekom-Smit LWA, Morris AD, Butler C, van der Wouden JC
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2009, Issue 1 http://www.thecochranelibrary.com
Interventions for impetigo (Review) Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Non-bullous impetigo: topical antibiotic versus placebo, Outcome 1 cure/improvement. Analysis 2.1. Comparison 2 Non-bullous impetigo: topical antibiotic versus another topical antibiotic, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.1. Comparison 3 Non-bullous impetigo: topical antibiotic versus oral antibiotic, Outcome 1 cure/improvement. Analysis 4.1. Comparison 4 Non-bullous impetigo: topical antibiotics versus disinfecting treatments, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.1. Comparison 5 Non-bullous impetigo: oral antibiotics versus placebo, Outcome 1 cure/improvement. . Analysis 6.1. Comparison 6 Non-bullous impetigo: oral antibiotic (cephalosporin) versus another oral antibiotic, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.1. Comparison 7 Non-bullous impetigo: oral cephalosporin versus other oral cephalosporin, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.1. Comparison 8 Non-bullous impetigo: oral macrolide versus penicillin, Outcome 1 cure/improvement. . Analysis 9.1. Comparison 9 Non-bullous impetigo: oral macrolide versus another oral macrolide, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 10.1. Comparison 10 Non-bullous impetigo: oral penicillin versus other oral antibiotic (including penicillin), Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 11.1. Comparison 11 Non-bullous impetigo: other comparisons of oral antibiotics, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.1. Comparison 12 Non-bullous impetigo: oral antibiotics versus disinfecting treatments, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.1. Comparison 13 Non-bullous impetigo: disinfecting treatments versus placebo, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.1. Comparison 14 Bullous impetigo: topical antibiotic versus another topical antibiotic, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 15.1. Comparison 15 Bullous impetigo: topical antibiotic versus oral antibiotic, Outcome 1 cure/improvement. Analysis 16.1. Comparison 16 Bullous impetigo; oral antibiotic versus another oral antibiotic, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 17.1. Comparison 17 Secondary impetigo: steroid versus antibiotic, Outcome 1 cure/improvement. . . . Analysis 18.1. Comparison 18 Secondary impetigo: steroid+antibiotic versus steroid, Outcome 1 cure/improvement. Analysis 19.1. Comparison 19 Secondary impetigo: steroid+antibiotic versus antibiotic, Outcome 1 cure/improvement. Analysis 20.1. Comparison 20 Secondary impetigo: oral antibiotic versus another oral antibiotic, Outcome 1 cure/improvement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 1 2 2 4 4 5 18 19 20 20 27 65 71 72 75 77 78 78 80 81 82 83 84 84 85 85 86 87 88 88 89 89 89 91 91 93 93 93
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INDEX TERMS
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[Intervention Review]
Interventions for impetigo

Sander Koning1 , Arianne P Verhagen1 , Lisette WA van Suijlekom-Smit2 , Andrew D Morris3 , Christopher Butler4 , Johannes C van der Wouden5
1 Department
of General Practice, Erasmus MC, University Medical Center, Rotterdam, Netherlands. 2 Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, Netherlands. 3 Department of Dermatology, University of Wales College of Medicine, Cardiff, UK. 4 Department of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK. 5 Department of General Practice, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands
Contact address: Sander Koning, Department of General Practice, Erasmus MC, University Medical Center, Room Ff337, PO Box 1738, Rotterdam, 3000 DR, Netherlands. s.koning@erasmusmc.nl. Editorial group: Cochrane Skin Group. Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009. Review content assessed as up-to-date: 26 November 2002. Citation: Koning S, Verhagen AP, van Suijlekom-Smit LWA, Morris AD, Butler C, van der Wouden JC. Interventions for impetigo. Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD003261. DOI: 10.1002/14651858.CD003261.pub2. Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT Background Impetigo is a common supercial bacterial skin infection, most frequently encountered in children. There is no standard therapy and guidelines for treatment differ widely. Treatment options include many different oral and topical antibiotics as well as disinfectants. Objectives To assess the effects of treatments for impetigo, including waiting for natural resolution. Search strategy We searched the Skin Group Specialised Trials Register (March 2002), Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1 2002), the National Research Register (2002), MEDLINE (from 1966 to January 2003), EMBASE (from 1980 to March 2000) and LILACS (November 2001). We handsearched the Yearbook of Dermatology (1938 to 1966), the Yearbook of Drug Therapy (1949 to 1966), used reference lists of articles and contacted pharmaceutical companies. Selection criteria Randomised controlled trials of treatments for non-bullous and bullous, primary and secondary impetigo. Data collection and analysis All steps in data collection were done by two independent authors. We performed quality assessments and data collection in two separate stages. Main results We included 57 trials including 3533 participants in total which studied 20 different oral and 18 different topical treatments. Cure or improvement Topical antibiotics showed better cure rates than placebo (pooled odds ratio (OR) 6.49, 95% condence interval (CI) 3.93 to 10.73), and no topical antibiotic was superior (pooled OR of mupirocin versus fusidic acid 1.76, 95% CI 0.69 to 2.16). Topical mupirocin
Interventions for impetigo (Review) Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1
was superior to oral erythromycin (pooled OR 1.22, 95% CI 1.05 to 2.97). In most other comparisons, topical and oral antibiotics did not show signicantly different cure rates, nor did most trials comparing oral antibiotics. Penicillin was inferior to erythromycin and cloxacillin and there is little evidence that using disinfectant solutions improves impetigo.
Side effects The reported number of side effects was low. Oral antibiotic treatment caused more side effects, especially gastrointestinal ones, than topical treatment. Authors conclusions Data on the natural course of impetigo are lacking. Placebo controlled trials are scarce. There is little evidence about the value of disinfecting measures. There is good evidence that topical mupirocin and topical fusidic acid are equally, or more effective than oral treatment for people with limited disease. It is unclear if oral antibiotics are superior to topical antibiotics for people with extensive impetigo. Fusidic acid and mupirocin are of similar efcacy. Penicillin was not as effective as most other antibiotics. Resistance patterns against antibiotics change and should be taken into account in the choice of therapy.
PLAIN LANGUAGE SUMMARY Interventions for the skin infection impetigo Impetigo causes blister-like sores. The sores can ll with pus and form scabs, and scratching can spread the infection. Impetigo is caused by bacteria, is contagious and usually occurs in young children. Treatment options include disinfectant solutions, antibiotic creams, steroid/antibiotic creams and oral antibiotics. The review of trials found that penicillin is not effective for impetigo, while other oral antibiotics can help. However, two antibiotic creams (mupirocin and fusidic acid) are at least as effective as oral antibiotics for limited disease. There is little evidence that using disinfectant solutions improves impetigo.
BACKGROUND
Description of the condition
Biology and symptoms Impetigo or impetigo contagiosa is a contagious supercial bacterial skin infection, most frequently encountered in children. It is typically classied as either primary impetigo (i.e. direct bacterial invasion of previously normal skin) or secondary or common impetigo, where the infection is secondary to some other underlying skin disease that disrupts the skin barrier, such as scabies or eczema. Impetigo is also classied as bullous or non-bullous impetigo. Bullous impetigo simply means that the skin eruption is characterised by bullae (blisters). The term impetigo contagiosa is
sometimes used to mean non-bullous impetigo, at other times it is used as a synonym for all impetigo. Non-bullous impetigo is the most common form of impetigo. The initial lesion is a thin-walled vesicle on previously normal skin that rapidly ruptures. It then leaves a supercial erosion covered with yellowish-brown or honey-coloured crusts. The crusts eventually dry, separate and disappear leaving a red mark that heals without scarring. The most frequently affected areas are the face and limbs. The lesions are sometimes painful. Usually, there are no systemic symptoms such as fever, malaise, or anorexia. Swelling of the lymph nodes draining the infected area of skin is common. It is believed that spontaneous resolution may be expected within two to three weeks without treatment in most cases, but that more prompt resolution occurs with adequate treatment. Diagnostic confusion can occur with a variety of skin disorders including shingles, cold sores, cutaneous fungal infections and eczema (Hay 1998; Resnick
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2000). Pyoderma is sometimes used as a synonym for impetigo in tropical countries, usually to denote streptococcal as opposed to staphylococcal impetigo. Bullous impetigo is characterised by larger bullae or blisters that rupture less readily and can persist for several days. Usually there are fewer lesions and the trunk is affected more frequently than in non-bullous impetigo. Diagnostic confusion can occur with thermal burns, blistering disorders (e.g. bullous pemphigoid) and Stevens Johnson syndrome.
year (McCormick 1995). In the Netherlands in the late 1980s the consultation rate was 2.2% of all children under 14 years ( Bruijnzeels 1993). Peak incidence occurs between the ages of two and six years (Bruijnzeels 1993). In some tropical or developing countries the incidence of impetigo seems to be higher than elsewhere. (Canizares 1993; Kristensen 1991).
Description of the intervention

Management options for impetigo include the following: 1. no treatment, waiting for natural resolution, hygiene measures; 2. topical disinfectants, such as saline, hexachlorophene, povidone-iodine and chlorhexidine; 3. topical antibiotics, such as neomycin, bacitracin, polymyxin B, gentamycin, fusidic acid, mupirocin or topical steroid/ antibiotic combination; 4. systemic antibiotics, such as penicillin, (u)cloxacillin, amoxicillin/clavulanic acid, erythromycin, cephalexin. The aims of treatment include resolving the soreness caused by lesions, and the unsightly appearance (especially on the face) and preventing recurrence and spread to other people. An ideal treatment should be effective, cheap, easy to use and accepted by people. It should be free from side effects, and should not contribute to bacterial resistance. For this reason antibiotics should not have an unnecessarily broad spectrum (Espersen 1998; Smeenk 1999) and if topical antibiotic is used it should preferably not be one which may be needed for systemic use (Carruthers 1988; Smeenk 1999). Waiting for natural resolution could be acceptable if the natural history were known and benign. Impetigo is considered to be self limiting by many authors (Hay 1998; Resnick 2000). However, there is no data on the natural history of impetigo. Reported cure rates of placebo creams vary from 8% to 42% at 7 to 10 days ( Eells 1986; Ruby 1973). Topical cleansing used to be advised 30 years ago as an alternative for antibiotic treatment, but is now said to be no more effective than placebo (Dagan 1992). Guidelines and treatment advice often do not mention topical cleansing as a treatment because frequently the main concern is preventing the spread of the infection to other children. A choice has to be made between topical and systemic antibiotic treatment although sometimes dual therapy is employed. An advantage of the use of topical antibiotics is that the drug can be applied where it is needed, avoiding side effects like gastrointestinal upsets. Also, compliance may be better (Britton 1990). The disadvantages of using topical antibiotics include the risks of developing bacterial resistance and of sensitisation i.e. developing an allergic contact dermatitis to one of the constituents of the topical preparation (Carruthers 1988; Smeenk 1999). This is especially common with the older antibiotics such as gentamycin, bacitracin and neomycin (Smeenk 1999). Some preparations (e.g. tetracycline) can cause staining of skin and clothes.
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Causes Staphylococcus aureus is considered to be the main bacterium that causes non-bullous impetigo. However Streptococcus pyogenes, or both S. pyogenes and S. aureus, are sometimes isolated. In moderate climates, staphylococcal impetigo is more common, whereas in warmer and more humid climates, the streptococcal form predominates. The relative frequency of S. aureus infections has also changed with time (Dagan 1993). It was predominant in the 1940s and 1950s, after which Group A streptococci became more prevalent. In the past two decades, S. aureus has become more common again. Bullous impetigo is always caused by S. aureus. Secondary impetigo may occur as a complication of many dermatological conditions, notably eczema. The eruption appears clinically similar to non-bullous impetigo. Usually S. aureus is involved. The underlying skin disease may improve with successful treatment of the impetigo and the converse may also be true. Complications of non-bullous impetigo are rare. Local and systemic spread of infection can occur which may result in cellulitis, lymphangitis or septicaemia. Non-infectious complications of S. pyogenes infection include guttate psoriasis, scarlet fever and glomerulonephritis (an inammation of the kidney that can lead to kidney failure). It is thought that most cases of glomerulonephritis result from streptococcal impetigo rather than streptococcal throat infection and this has always been an important rationale for antibiotic treatment. The incidence of acute glomerulonephritis has declined rapidly over the last few decades. Baltimore 1985 stated that the risk of developing glomerulonephritis is not altered by treatment of impetigo; however, certain subtypes of Group A streptococci are associated with a much greater risk (Dillon 1979).
Epidemiology In the Netherlands, most people with impetigo consult their general practitioner and approximately 1% of the cases are referred to a dermatologist (Bruijnzeels 1993). Although the incidence has declined slightly, impetigo is still a common disease, particularly in young children. It is the third most common skin disorder in children after dermatitis/eczema and viral warts (Bruijnzeels 1993; Dagan 1993). In British general practice 2.8% of children aged 0 to 4 and 1.6% aged 5 to 15 consult their GP about impetigo each
Staphylococcal resistance against penicillin and erythromycin is common (Dagan 1992). Bacterial resistance against the newer topical antibiotics, such as mupirocin ointment and fusidic acid ointment, is still limited (de Neeling 1998). Another advantage of the newer topical antibiotics is that mupirocin is never, and fusidic acid not often, used systemically.
Types of interventions Any program of topical or systemic (oral, intramuscular or intravenous) treatment, including antibiotics, disinfectants or any other intervention for impetigo, including awaiting natural response.
Types of outcome measures
How the intervention might work

All treatment options listed above aim at either eradicating the bacteriae or preventing the bacteriae to duplicate.
Primary outcomes
Why it is important to do this review

Guidelines concerning treatment vary widely. Some recommend oral antibiotic treatment, others local antibiotic treatment, or even just disinfection in mild cases (Boukes 1999; Hay 1998; Resnick 2000), so doctors have many treatment options. The evidence on what works best is not clear. There is potential conict between what is in the best interest of the individual patient, and what would best benet the community in terms of cost and induction of antibiotic resistance.
1. Cure as dened by clearance of crusts, blisters and redness as assessed by the investigator. 2. Relief of symptoms such as pain, itching and soreness as assessed by participants.
Secondary outcomes
1. Recurrence rate. 2. Adverse effects such as pain, allergic sensitisation and complications. 3. Development of bacterial resistance.
Search methods for identication of studies OBJECTIVES

To assess the effects of treatments for impetigo, including waiting for natural resolution. Electronic searches (a) The Cochrane Skin Group Specialised Register was searched (March 2002) please see Appendix 1. (b) The Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2002) and the National Research Register (2002) were both searched, please see Appendix 2. (c) MEDLINE was searched (from 1966 to January 2003) please see Appendix 3. (d) EMBASE was searched (from 1980 to March 2000) please see Appendix 4. (e) LILACS (November 2001) was searched please see Appendix 5. (f ) The metaRegister of Controlled Trials on the Current Controlled Trials web site http://www.controlled-trials.com was searched please see Appendix 6. The above electronic searches will be repeated each year in May.
METHODS
Criteria for considering studies for this review
Types of studies Randomised trials. Types of participants People who have impetigo or impetigo contagiosa diagnosed by a doctor, and preferably conrmed by bacterial culture. We recorded whether or not bacterial culture was performed. The diagnosis could be either non-bullous or bullous impetigo. Studies using a broader diagnostic category such as bacterial skin infections or pyoderma were eligible if a specic subgroup with impetigo could be identied, for which the results were separately described. Studies on secondary impetigo or impetiginised dermatoses were included.
Searching other resources
Handsearching
We handsearched the Yearbook of Dermatology (1938 to 1966) and the Yearbook of Drug Therapy (1949 to 1966).
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References from published studies
References from published studies, including secondary review articles, were checked for further studies.
randomisation procedure; allocation concealment; intention-to-treat analysis; baseline comparison of severity of disease.
Unpublished literature
Unpublished, ongoing trials, and grey literature were searched for via correspondence with authors and pharmaceutical companies.
Language
No language restrictions were applied.
Data collection and analysis
Selection of studies Two authors (JCvdW and SK) independently read all abstracts or citations of trials. If one of the authors thought the article might be relevant, a full copy of the article was acquired for further data collection. The reasons for exclusion were recorded for every excluded abstract or citation. Only full reports were included. All full copy articles were independently screened by two authors (LvSS and SK). The articles were selected according to the earlier dened inclusion criteria. The reason for exclusion for every paper was recorded on a specially designed registration form (see the Characteristics of excluded studies table). In case of doubt, the opinion of a third author was obtained (JCvdW). Many trials studied a range of (skin) infections including impetigo. Frequently, the results of the subgroup of impetigo participants were not reported separately. In these studies, provided they were published in the last ve years, trial authors were contacted and asked to provide the results of the subgroup of impetigo participants. Only in one instance were data obtained in this way (Blaszcyk 1998). Data extraction and management Two authors (ADM and CCB), using a pre-piloted data abstraction form, carried out the full data extraction. The form contained key elements such as time and setting of the study, patient characteristics, bacterial characteristics, type of interventions, outcomes, and side effects. Any disagreements were managed with the help of a third author (SK). Assessment of risk of bias in included studies
These criteria were applied using both the Jadad and the Delphi quality assessment lists. The Jadad list consists of three items, directly related to the reduction of bias (Jadad 1996). The Delphi list was recently developed by an international panel of more than 25 experts in the eld of quality assessment of RCTs (Verhagen 1998). The list contains nine items and measures three dimensions of quality: internal validity, external validity and statistical considerations. Studies that scored at least 50% of the maximum available scores on both lists were (arbitrarily) considered good. For feasibility reasons, the assessment was not performed under masked conditions. There is no consensus whether assessment should be done blinded for authors, institutions, journal, publication year ( Jadad 1998). Assessment of heterogeneity The I2 statistic was used to assess statistical heterogeneity, with I2 > 50% being regarded as signicant heterogeneity. Data synthesis Where there was no statistical evidence of heterogeneity we used xed effect models to estimate effects. Otherwise, random effect models were used. Odds ratios with 95% condence intervals were used as effect measures for dichotomous outcomes. Sensitivity analysis Prespecied factors for sensitivity analyses were: 1. the quality of the studies; 2. whether there was observer blinding; 3. whether there was just a clinical diagnosis or bacterial swab conrmation; 4. primary versus secondary impetigo; 5. bullous versus non-bullous; 6. staphylococcal or streptococcal predominance. When we analysed the data we decided to consider the results for bullous and non bullous impetigo separately.
RESULTS
Assessment of methodological quality
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies.
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Two independent authors (JCvdW and AV) assessed the methodological quality of the trials. The following items were addressed:
Results of the search Approximately 700 studies were identied, 221 of which were selected for full copy reading.
Included studies Fifty-six papers were eventually included, describing 57 trials. The studies had a total of 3533 evaluable participants, an average of 62 participants per study (see the Characteristics of included studies). Only two studies on bullous impetigo were included ( Dillon 1983; Moraes Barbosa 1986). Four trials included both bullous and non bullous impetigo participants (Barton 1989; Dagan 1992; Pruksachat. 1993; Park 1993). Two studies on secondary impetigo were included (Fujita 1984; Wachs 1992). Two other trials included both primary and secondary impetigo participants ( Gonzalez 1989; Tamayo 1991). Thirty-two trials studied impetigo alone, whereas 25 trials studied participants with a range of (usually skin) infections, impetigo being 1 of them. This was the typical study design when a new antibiotic was studied. This type of study design imposed problems in retrieving outcome data, as the outcomes were often presented for all the participants together. We included these studies only if the main outcome measure was presented separately for the subgroup of impetigo participants. Twenty-ve of the studies were carried out in North America (Canada/northern states 13, Southern states 8, multicentre 4), 14 in Europe, 9 in Central/South America, 5 in Asia, 2 in Israel, and 2 were multicentre worldwide trials. Most trials were reported in the English language. Other languages included were Japanese (three), Korean, Thai, Portuguese, Spanish and Danish (one each). Some had abstracts and tables in English. Trials in Russian, German and French were among those that were excluded (not for language reasons). In instances where none of the authors were competent in the language of the paper, translators provided assistance. An appreciable number of studies from the early 1940s were found (e.g. MacKenna). These studies were often carried out in military populations, where impetigo was a frequent disease. These study reports did not meet the inclusion criteria of our review, because of inadequate randomisation. Most included studies were published between 1985 and 1994 (43/57), with a peak in the late 1980s. Five included studies evaluating mupirocin were presented at an international symposium in 1984. We found no publication other than the conference proceedings for three of these (Kennedy 1985; Rojas 1985; Wainscott 1985). Two were published elsewhere as well (Eells 1986; Gould 1984). The 57 trials evaluated 38 different treatments (20 oral treatments and 18 topical treatments, both including placebo). Only oral systemic treatments were studied. A total of 53 different comparisons were made. Some comparisons were made in several studies; some studies made more than one comparison. Forty-ve comparisons were made only once. Eight different comparisons were made in more than one trial, especially when topical mupirocin was
studied (topical mupirocin versus oral erythromycin: 11 studies, mupirocin versus fusidic acid: 4 studies, mupirocin versus placebo: 3 studies). For each of these comparisons, we pooled the outcomes of the different studies (see Data and analyses). The most common type of comparison was between two different oral antibiotic treatments (25 studies). Cephalosporins (16 studies) and macrolide antibiotics, especially erythromycin and azithromycin (10 studies) were most often involved. A topical antibiotic treatment was compared with an oral antibiotic treatment in 22 studies. Nineteen of these comparisons contained either erythromycin, mupirocin, or both. Only two trials studied antiseptic or disinfecting treatments ( Christensen 1994; Ruby 1973). Few placebo controlled trials were found (Eells 1986; Gould 1984; Koning 2002; Rojas 1985; Ruby 1973). The latter is the only trial that compared an oral treatment with placebo. There were important design differences between the studies. As mentioned before, many trials included participants with infections other than impetigo, while some trials studied only impetigo. Most studies were carried out in hospital out-patient clinics (paediatrics or dermatology, 49 studies), although some were carried out in General Practice. Ages of included participants differed widely, as some studies were carried out exclusively in either adults or children. The average age of study participants in trials that studied a range of skin infections were usually higher than in studies focusing on impetigo alone. With the exception of two studies (Rice 1992; Vainer 1986), all studies performed bacteriological investigations. Although a number of studies explicitly stated that participants with a negative culture were excluded, other studies may also have excluded culture negative participants without reporting those exclusions. No study reported a predominantly streptococcal impetigo. The only studies not to report a preponderance of staphylococcal impetigo were Mertz 1989 and Ruby 1973 (carried out in Puerto Rico and Texas respectively). Cure as assessed by investigator was our main outcome measure. This was often not dened. Researchers sometimes combined the categories cured and improved and presented those participants as one group. The length of follow-up varied widely and was sometimes not even specied, however we tried to retrieve the data for follow up as close as possible to seven days after the start of treatment. Bacterial resistance rate at baseline, or subsequent development of resistance was not often reported. Four additional studies have recently been found and are awaiting assessment.
Excluded studies One hundred and sixty-ve of these studies did not meet the inclusion criteria (see the Characteristics of excluded studies). The most common reasons were: the study was not about impetigo, or the outcomes of impetigo participants were not reported separately, or studies were not randomised.
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Risk of bias in included studies

The criteria that are used for the Delphi and Jadad quality scales are listed in Table 1 (Content of Quality Score Lists). The scores given using these scales are shown in Table 2 (Delphi Quality Score) and Table 3 (Jadad Quality Score). Twelve of the 57 studies are considered good according to our predetermined criterion of scoring 50% or higher on both quality scales (Bass 1997; Blaszcyk 1998; Britton 1990; Dagan 1992; Jaffe 1986; Kiani 1991; Koning 2002; Koranyi 1976; McLinn 1988; Nolting 1988; White 1989). There was no relation between quality of the study and publication year. Table 1. Content of Quality Score Lists Abbreviation D1a D1b D2 D3 D4 D5 D6 D7 D8 J1a J1b J2a J2b J3 Item Was a method of randomisation performed? Was the treatment allocation concealed? Were the groups similar at baseline concerning the most important prognostic characteristics? Were both inclusion and exclusion criteria specied? Was the outcome assessor blinded? Was the care provider blinded? Was the patient blinded? Were point estimates and measures of variability presented for primary outcome measures? Did the analysis include an intention-to-treat-analysis? Was the study described as randomised? Is the method appropriate? Was the study described as double blind? Is the method appropriate? Was there a description of withdrawals and drop-outs?
Table 2. Delphi Quality Score study ID D1a ran- D1b dom. conceal ment ? ? D2 base- D3 crite- D4 asses- D5 line ria sor blind provider blind + ? ? ? D6 patient blind ? D7 D8 point es- ITT tim analysis + totals
Arata 1989a Arata 1989b
+ Arredondo 1987 Barton 1987 Barton 1988 Barton 1989 +
Bass 1997 + Beitner 1996 Blaszcyk 1998 Britton 1990 Christensen 1994 Dagan 1989 Dagan 1992 Daniel 1991a (1st study) +
? ?
+ +
+ ?
+ ?
+ ?
+ +
6 3
Table 2. Delphi Quality Score
(Continued)
Daniel 1991b (2nd study) Demidovich 1990 Dillon 1983 Dux 1986 Eells 1986 Esterly 1991 Fujita 1984 Gilbert 1989 Ginsburg 1978 Goldfarb 1988 Gonzalez 1989 Gould 1984 Gratton 1987 Hains 1989 Jaffe 1985
(Continued)
Jaffe 1986 Kennedy 1985 Kiani 1991 Koning 2002 Koranyi 1976 McLinn 1988 Mertz 1989 Montero 1996 Moraes Barbosa 1986 Morley 1988 Nolting 1988 Park 1993 Pruksachat. 1993 Rice 1992 Rodriguez 1993 Rojas 1985
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(Continued)
Ruby 1973 Sutton 1992 Tack 1997 Tack 1998 Tamayo 1991 Tassler 1993 Vainer 1986 Wachs 1976 Wainscott 1985 Welsh 1987 White 1989 Wilkinson 1988
Table 3. Jadad Quality Score Randomised? J1a randomised? ? + J1b appropiate? J2a doubleblind? ? ? + + J2b appropiate? J3 withdrawal? Total score
Arata 1989a Arata 1989b
? ?
+ ?
2 2
11
Table 3. Jadad Quality Score
(Continued)
Arredondo 1987 + Barton 1987 Barton 1988 Barton 1989 Bass 1997 Beitner 1996 Blaszcyk 1998 Britton 1990 Christensen 1994 Dagan 1989 Dagan 1992 Daniel 1991a Daniel 1991b Demidovich 1990 Dillon 1983 Dux 1986 Eells 1986 Esterly 1991 Fujita 1984 Gilbert 1989 Ginsburg 1978 Goldfarb 1988 Gonzalez 1989 Gould 1984 + + + + + + + +
? + + ? + ? ? + +
+ + + + + +
? ? ? + ? + ? -
+ ? + + + +
1 4 3 1 5 1 4 4 4
+ + + + +
+ + + + ?
+ + -
+ -
+ + + + -
4 5 3 3 1
+ + + + + + + + + +
+ ? + ? ? ? ? ? ? +
+ + + + +
? ? ? ? ? ? ? ? ?
+ + + + + + +
3 2 4 2 3 2 1 2 2 4
12
(Continued)
Gratton 1987 Hains 1989 Jaffe 1985 Jaffe 1986 Kennedy 1985 Kiani 1991 Koning 2002 Koranyi 1976 McLinn 1988 Mertz 1989 Montero 1996
+ + + + + + + + + + +
? ? ? + ? + + + + + ? ?
+ + + + + -
? ? + + ? + + ? -
+ + ? + + + + + + -
1 2 3 5 2 5 5 3 3 3 2 1
Moraes Barbosa + 1986 Morley 1988 Nolting 1988 Park 1993 Pruksachat. 1993 Rice 1992 Rodriguez 1993 Rojas 1985 Ruby 1973 Sutton 1992 Tack 1997 Tack 1998 + + + +
? + ? ?
+ -
? ? -
+ ?
1 4 1 1
+ + ? + + + +
? ? ? + + ? -
+ + +
? ? +
+ + + + + +
2 2 1 3 4 2 4
13
(Continued)
Tamayo 1991 Tassler 1993 Vainer 1986 Wachs 1976 Wainscott 1985 Welsh 1987 White 1989 Wilkinson 1988
+ + + + + + + +
? ? + ? + ? + ?
+ +
? ?
+ + ? + + + -
2 2 2 2 3 2 3 2
Allocation All included studies were described as randomised, as this was a selection criterion. However, most papers did not describe the method of the randomisation, so that the method could not be judged as appropriate (32 of 57). Of the papers that did describe the method, the method was usually considered appropriate (24 of 25). Only 18 of the 57 studies provided information on allocation concealment. In most cases (11 of 18), treatment allocation was not concealed.
Effects of interventions
Clinical cure The rst primary outcome was clinical cure (or improvement) at one week from commencement of treatment, as assessed by the investigator.
(a) Non-bullous impetigo Blinding A minority of studies (23 of 57) was described as double-blind. In only eight of these double-blinded studies, was the method considered appropriate. It was not always clear whether the patient, the care provider and the outcome assessor were all blinded (n = 13,15,14).
(i) Topical antibiotics
Topical antibiotics versus placebo (ve studies) Overall topical antibiotics showed better cure rates or more improvement than placebo (odds ratio (OR) 6.49, 95% condence interval (CI) 3.93 to 10.73; Analysis 1.1). This result was consistent for mupirocin (OR 5.40, 95% CI 2.79 to 10.45; 3 studies - Eells 1986; Gould 1984; Rojas 1985; Analysis 1.1) and fusidic acid (OR 8.65, 95% CI 3.88 to 19.29; 1 study - Koning 2002; Analysis 1.1). In one small study (Ruby 1973), bacitracin did not show a difference in cure rate compared with placebo (OR 3.97, 95% CI 0.15 to 104.18; Analysis 1.1).
Incomplete outcome data In some studies, high numbers lost to follow up were recorded. Only eight studies included an intention-to-treat analysis. For some other studies, an intention-to-treat analysis may be calculated from the data presented in the study. We did not construct intention to treat analyses ourselves.
14
Topical antibiotic versus another topical antibiotic (twelve studies) No one topical antibiotic clearly showed superiority over another. There were 10 different comparisons: 4 studies (Gilbert 1989; Morley 1988; Sutton 1992; White 1989) compared mupirocin with fusidic acid (OR 1.22, 95% CI 0.69 to 2.16; Analysis 2.1), and the remaining 9 were all only represented by a single small study.
A single study (Ruby 1973) was inconclusive, detecting no signicant difference between oral penicillin and placebo (OR 9.26, 95% CI 0.44 to 192.72; Analysis 5.1).
Oral antibiotic versus another oral antibiotic: cephalosporin versus another antibiotic (seven studies) All comparisons consisted of single studies (or arms of a single study), with only one comparison (cefuroxim versus erythromycin) showing a signicant difference in favour of cefuroxim (OR 6.40, 95% CI 1.44 to 28.44; Park 1993; Analysis 6.1).
Topical antibiotics versus oral (systemic) antibiotics (sixteen studies) Pooling of ten studies which compared mupirocin with oral erythromycin showed signicantly better cure rates or more improvement with mupirocin (OR 1.76, 95% CI 1.05 to 2.97; Analysis 3.1). However no signicant differences were seen between mupirocin and dicloxacillin (Arredondo 1987), cephalexin (Bass 1997) or ampicillin (Welsh 1987). Fusidic acid was signicantly better than erythromycin in one study (Park 1993), but no difference was seen between fusidic acid and cefuroxim in another arm of the same study. Bacitracin was signicantly worse than oral cephalexin in one small study (Bass 1997), but no difference was seen between bacitracin and erythromycin (Koranyi 1976), or penicillin (Ruby 1973). A sensitivity analysis on the inuence of the quality score on the comparison mupirocin versus erythromycin (ten studies) revealed that there was no clear relation between the quality score of the study and the outcome. In meta-analysis, the three studies of good quality (Britton 1990; Dagan 1992; McLinn 1988) revealed a better cure rate of mupirocin compared to erythromycin (OR 3.73 95% CI 1.35 to 10.34; Analysis 3.1). The odds ratio for the overall analysis of ten studies also shows benet for mupirocin, but not to such a degree as the three good quality studies.
Oral antibiotic versus another oral antibiotic: one cephalosporin versus another cephalosporin (four studies) No signicant differences were seen between cephalexin and cefadroxil (Hains 1989), or cefdinir (two studies - Tack 1997; Tack 1998); or between cefaclor and cefdinir (Arata 1989a), please see Analysis 7.1.
Oral antibiotic versus another oral antibiotic: macrolide versus penicillin (six studies) In two studies (Barton 1987; Demidovich 1990), erythromycin showed a better cure rate or more improvement than penicillin (OR 8.82, 95% CI 1.49 to 52.01; Analysis 8.1). The other four comparisons consisted of single studies and did not show signicant differences between macrolides and penicillins.
Oral antibiotic versus another oral antibiotic: macrolide versus another macrolide (one study) In a single study (Daniel 1991a), no difference in cure rate or improvement was seen between azithromycin and erythromycin (OR 1.90, 95% CI 0.62 to 5.83; Analysis 9.1).
Topical antibiotics versus disinfecting treatment (two studies) In one study (Ruby 1973), no statistically signicant difference in cure/improvement was seen when bacitracin was compared to hexachlorophene (OR 3.97, 95% CI 0.15 to 104.18; Analysis 4.1). In another study (Christensen 1994), there was a tendency for fusidic acid cream to be more effective than hydrogen peroxide, but this did not quite reach statistical signicance (OR 1.79, 95% CI 0.99 to 3.25; Analysis 4.1). When the two studies were pooled, topical antibiotics were signicantly better than disinfecting treatments (OR 1.84, 95% CI 1.03 to 3.29; Analysis 4.1).
Oral antibiotic versus another oral antibiotic: penicillin versus other oral antibiotics (including other penicillins) (four studies) Amoxicillin plus clavulanic acid showed a better cure rate than amoxicillin alone in one study (Dagan 1989; OR 9.80, 95% CI 1.09 to 88.23; Analysis 10.1), but when amoxicillin plus clavulanic acid was compared with eroxacin in another study (Tassler 1993), no signicant difference was seen (OR 1.68, 95% CI 0.37 to 7.63; Analysis 10.1). Cloxacillin was signicantly superior to penicillin in two studies (Gonzalez 1989; Pruksachat. 1993: (pooled OR 13.74, 95% CI 4.36 to 43.24; Analysis 10.1).
15
(ii) Oral antibiotics
Oral antibiotics versus placebo (one study)
Other comparisons of oral antibiotics (one study) In a single small study (Arata 1989b), no difference in cure rates/ improvement could be detected between lomeoxacin and noroxacin (OR 2.50, 95% CI 0.37 to 16.89; Analysis 11.1).
(ii) Oral antibiotics
Oral antibiotic versus another oral antibiotic (one study) No signicant difference was seen between cephalexin and dicloxacillin (Dillon 1983; OR 3.39, 95% CI 0.62 to 18.49; Analysis 16.1).
Oral antibiotics versus disinfecting treatments (one study) In a single small study (Ruby 1973), no difference in cure rates/ improvement could be detected between penicillin and hexachlorophene (OR 9.26, 95% CI 0.44 to 192.72; Analysis 12.1).
(c) Secondary impetigo
(iii) Disinfecting treatments
(i) Topical antibiotics
Disinfecting treatments versus placebo (one study) In a single small study (Ruby 1973), no participants in either the hexachlorophene or placebo group showed cure or improvement (Analysis 13.1). Comparisons of disinfecting treatments with antibiotics are given above.
Antibiotic versus steroid versus antibiotic plus steroid (one study) In a three-armed study (Wachs 1976), the combination of betamethasone and gentamycin cream was signicantly more effective than gentamycin alone (OR 6.11, 95% CI 1.84 to 20.31; Analysis 19.1). The comparisons of betamethasone with gentamycin alone or with betamethasone plus gentamycin did not show signicant differences (Analysis 17.1; Analysis 18.1).
(b) Bullous impetigo
(ii) Oral antibiotics (i) Topical antibiotics
In a very small study, no difference was detected between cephalexin and enoxacin (Fujita 1984) (Analysis 20.1).
Topical antibiotics versus other topical antibiotics (one study, three comparisons) In a small study (Moraes Barbosa 1986), fusidic acid was signicantly more effective than both neomycin/bacitracin (OR 55.00, 95% CI 4.30 to 703.43; Analysis 14.1) and chloramphenicol (OR 25.00, 95% CI 2.92 to 213.99; Analysis 14.1). In the same study no difference was detected between chloramphenicol and neomycin/bacitracin (OR 2.20, 95% CI 0.17 to 28.14; Analysis 14.1).
Other outcomes The second primary outcome was relief of symptoms.This was recorded by only a few studies, and is therefore not reported here. No relevant data were provided by any study for either the rst (recurrence rates) or third (development of bacterial resistance) secondary outcome. The second secondary outcome was adverse effects
Adverse effects Topical antibiotics versus oral antibiotics (one study, three comparisons) The same study (Moraes Barbosa 1986) showed that oral erythromycin was signicantly more effective than both neomycin/ bacitracin (OR 0.06, 95% CI 0.01 to 0.68; Analysis 15.1) and chloramphenicol (OR 0.14, 95% CI 0.02 to 0.96; Analysis 15.1). There was no signicant difference between fusidic acid and erythromycin (OR 3.57, 95% CI 0.53 to 23.95; Analysis 15.1).
(a) Disinfecting treatments
Eleven percent of the participants using hydrogen peroxide cream reported mild side effects (not specied) versus seven percent in the fusidic acid group (Christensen 1994). No patient was withdrawn from the study because of side effects. No adverse effects of scrubbing with hexachlorophene were recorded (Ruby 1973).
16
(b) Antibiotics
(iii) Oral treatments Eleven of the 26 trials comparing oral antibiotics did not report on side effects. Two of the 5 trials that studied erythromycin recorded side effects: only 1 of 54 (2%) participants reported gastrointestinal side effects. The other trials, usually making unique comparisons, mainly reported gastrointestinal side effects in small percentages. In four trials, a considerable difference in side effects was reported. Gastrointestinal complaints were recorded in 1 out of 113 (10%) in the enoxacin group compared to 4 out of 110 (4%) in cefalexin-treated participants (Fujita 1984). Fourteen of 327 (4%) of the cefadroxil-treated participants versus 2 of 234 (1%) of ucloxacillin participants had severe side effects such as stomach ache, rash, fever, vomiting (Beitner 1996). Cefaclor caused more diarrhoea than amoxicillin plus clavulanic acid (5 out of 16, 31% versus 2 out of 18, 11%) (Jaffe 1985). Finally, the clindamycin group of participants reported more side effects (any side effect) than the dicloxacillin treated group (Blaszcyk 1998). Sponsored research Industry sponsorship or organisation of the trial was declared to be present in 14 trials (25%). Four mupirocin studies (Goldfarb 1988; Mertz 1989; Wainscott 1985; White 1989), two with cefdinir (Tack 1997; Tack 1998), two with cefadroxil (Beitner 1996; Hains 1989), two with azithromycin (Daniel 1991a; Daniel 1991b), one amoxicillin plus clavulanic acid (Jaffe 1985), cefalexin (Dillon 1983), clindamycin (Blaszcyk 1998), and fusidic acid ( Sutton 1992). Five trials (9%) had been supported by other organisations. In the remaining 38 (67%) trials, no statement of sponsorship or funding was made (see Table 4, Declared sponsorship or funding).
(i) Topical treatments The trials included in this review usually reported few, if any, side effects from topical antibiotics. The studies comparing mupirocin, bacitracin and placebo reported none (Eells 1986; Ruby 1973) The study that compared fusidic acid to placebo recorded more side effects in the placebo group (Koning 2002). Three of four studies comparing mupirocin with fusidic acid recorded side effects: minor skin side effects were reported for mupirocin by 10 out of 368 (3%) participants and for fusidic acid by 4 out of 242 (2%) participants. Most other trials comparing topical antibiotics reported no side effects, or reported minor skin side effects in low numbers (less than 5% of participants).
(ii) Topical versus oral treatments Of the ten trials comparing erythromycin with mupirocin, nine reported side effects. With the exception of two trials (Britton 1990: equally divided minor gastrointestinal side effects, Rice 1992: nil reported), all trials recorded more side effects from erythromycin. Gastrointestinal side effects (nausea, stomach ache, vomiting, diarrhoea) were recorded in 80 of 297 (27%) participants in the erythromycin groups versus 17 of 323 (5%) participants in the mupirocin groups. Skin side effects (itching, burning) were recorded in 5 out of 297 (2%) in the erythromycin groups versus 23 out of 323 (7%) in the mupirocin groups. Most other trials comparing topical and oral antibiotics did not record data on side effects. Table 4. Declared sponsorship or funding Study Barton 1987 Barton 1988 Barton 1989 Beitner 1996 Blaszcyk 1998 Britton 1990 Daniel 1991a; Daniel 1991b Sponsor (product) Fleur de Lis Foundation Warner-Lambert Corporation Warner- Lambert Corporation Bristol-Myers Squibb (cefadroxil) Pharmacia & Upjohn Asia (clindamycin) US Navy Bureau of Medicine and Surgery Clinical Investigation Program Pzer Central Research (azithromycin)
17
Table 4. Declared sponsorship or funding
(Continued)
Dillon 1983 Goldfarb 1988 Hains 1989 Jaffe 1985 Koning 2002 Mertz 1989 Sutton 1992 Tack 1997 Tack 1998 Wainscott 1985 White 1989
Eli Lilly Research (cephalexin) Beecham Laboratories (mupirocin) Bristol-Myers Squibb (cefadroxil) Beecham Laboratories (amoxicillin+clavulanic acid) Dutch College of General Practitioners Beecham Laboratories (mupirocin) Leo Laboratories (fusidic acid) Parke-Davis pharmaceutical research (cefdinir) Parke-Davis pharmaceutical research (cefdinir) Beecham Pharmaceuticals (mupirocin) Beecham Pharmaceuticals (mupirocin) day). Cure rates of specic treatments can be different between studies, e.g. of fusidic acid and mupirocin (Sutton 1992; White 1989). This may explained by the fact that investigations were done in different regions and times, and that inclusion criteria differ.
We planned to do several sensitivity analyses. However, most trials were observer blind, took bacterial swabs, studied primary impetigo, and had staphylococcal predominance. Sensitivity analyses for these items were therefore not possible.
DISCUSSION
The large number of treatments evaluated (36) supports the view that there is no standard therapy for impetigo. Most studies did not contribute to clear answers about the vast choice of treatment options. Many studies were under powered. This is partly due to the fact that many trials included several skin infections, impetigo being only one of them. These studies are directed at the drug rather than at the disease. In many cases, signicant differences became insignicant when impetigo participants were considered after excluding participants with other sorts of infection. Another drawback of this type of study is that the age of participants is much higher than the typical impetigo patient (e.g. Blaszcyk 1998; Kiani 1991). The dosage of studied antibiotics may differ between studies, complicating the comparability of studies. However, the same doses were usually used (e.g. erythromycin 40 mg per kg per
Little is known about the natural history of impetigo. Therefore, the scarcity of placebo controlled trials is striking, given that impetigo can be considered a minor disease. Only ve placebo controlled studies have been conducted (Gould 1984; Eells 1986; Koning 2002; Rojas 1985; Ruby 1973). The 7 day cure rates of placebo groups in these studies vary but can be considerable (0 to 42%).
The disinfectant agents, such as povidone-iodine and chlorhexidine, recommended in some guidelines (Boukes 1999; Hay 1998; Resnick 2000), usually as supplementary treatment, have been inadequately studied, and have not been compared to placebo treatment. Hydrogen peroxide cream was not signicantly less effective (cure rate 72% versus 82%) than fusidic acid in a relatively large
18
trial (Christensen 1994). We judged that blinding in this trial was inadequate. Topical mupirocin and fusidic acid can be considered as effective as, or more effective than oral antibiotics, and these topical agents have fewer side effects. This nding is in sharp contrast to the commonly held view that oral treatment is superior to topical treatment (Baltimore 1985; Tack 1998). Other topical antibiotics were generally inferior to mupirocin, fusidic acid, and oral antibiotics. The study by Vainer is an exception: no difference was seen between tetracycline/bacitracin cream, neomycin/bacitracin cream and fusidic acid (Vainer 1986). Fusidic acid and mupirocin are the only topical antibiotics that have been compared to placebo (and shown to be more effective). A striking nding is that the trials comparing erythromycin with mupirocin recorded more (gastrointestinal) side effects in the erythromycin group than the trials that compared erythromycin with other oral antibiotics. None of the studies reported cases of acute (post streptococcal) glomerulonephritis. This complication has always been an important rationale for oral antibiotic treatment. The apparent absence of glomerulonephritis may reect the reduced importance of streptococci in impetigo. It should be noted that study sizes are small and glomerulonephritis is rare. There is a commonly accepted idea that more serious forms of impetigo (e.g. participants with extensive lesions, general illness, fever) need oral rather than topical treatment. This principle cannot be evaluated using the data included in our review, as trials that study local treatments usually exclude participants with more serious forms of impetigo. Resistance patterns of staphylococci causing impetigo change over time. Outcomes of studies dating back more than ten years, which form the majority of trials in this review, may not be applicable to the current prevalence of infecting agents. Also, resistance between regions and countries may vary considerably. Thus, up-to-date local characteristics and resistance patterns of the causative bacteria should always be taken into account when choosing antibiotic treatment. In addition, health authorities and other relevant bodies may advise against prescribing certain antibiotics for impetigo in order to restrict the development of bacterial resistance and reserve these drugs for more serious infections.
There is no evidence for the value of disinfecting measures in the treatment of impetigo, as 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 and mupirocin 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

There is good evidence that the topical antibiotics mupirocin and fusidic acid are equal to or possibly more effective than oral treatment. The only oral antibiotic that has been compared to placebo is penicillin, in an old study (Ruby 1973); there is no evidence that it is effective. Based on the available evidence on efcacy, no clear preference can be given for B-lactamase resistant narrow-spectrum penicillins such as cloxacillin, dicloxacillin and ucloxacillin, broad spectrum penicillins such ampicillin and amoxicillin plus clavulanic acid, cephalosporins, and macrolides. Other criteria such as price, (unnecessary) broadness of spectrum and wish to reserve a particular antibiotic can be decisive. Resistance rates against erythromycin seem to be rising. In general, oral antibiotics have more side effects, especially gastrointestinal ones. There is insufcient 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 compare treatments for a specic disease, rather than the effectiveness of a specic antibiotic on a variety of (skin) infections. As seen in this review, trials that study one treatment for several diseases, often show inconclusive results for specic diagnoses. Future research on impetigo should make a careful power calculation as most included studies were too small to be able to assess any difference in treatment effect. Research trying to establish the natural course of impetigo would be useful. But although impetigo can be considered a minor ailment, studies with a non-intervention arm seem ethically impracticable. The relative absence of data on the efcacy of topical disinfectants should urge future researchers to study these, since they do not contribute to antibiotic resistance and are cheap. This research may be of particular importance for developing countries. A trial on impetigo should preferably:
19
AUTHORS CONCLUSIONS Implications for practice
Implications for topical disinfectants in clinical practice
not combine data for several skin diseases, or both bullous and non-bullous impetigo, and primary and secondary impetigo. present results separately if it does study several diseases. report resistance rates of causative bacteria against the studied antibiotic and against reference antibiotics such as erythromycin, mupirocin and/or fusidic acid. use clear and objective outcome measures for cure and improvement of impetigo, instead of subjective judgements such as improved, satisfactory, good response. Key elements dening 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, i.e. 7, 14, 21 days will facilitate the comparison of studies. 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.
ACKNOWLEDGEMENTS
The authors would like to thank the following people from the editorial base for their substantial contribution to this review: Philippa Middleton and Tina Leonard. The editorial base would like to thank the following people who were the external referees for this protocol: David Little and William Noble (content experts), Carole Coupland (statistician) and Philip Pocklington (consumer).
REFERENCES
References to studies included in this review

Arata 1989a {published data only} Arata J, Kanzaki H, Kanamoto A, Okawara A, Kato N, Kumakiri M, et al.Double-blind comparative study of cefdinir and cefaclor in skin and skin structure infections. Chemotherapy 1989;37:101642. Arata 1989b {published data only} Arata J, Yamamoto Y, Tamaki H, Okawara A, Fukaya T, Ishibashi Y. Double-blind study of lomeoxacin versus noroxacin in the treatment of skin and soft tissue infections. Chemotherapy 1989;37: 482503.
Arredondo 1987 {published data only} Arredondo JL. Efcacy and tolerance of topical mupirocin compared with oral dicloxacillin in the treatment of primary skin infections. Current Therapeutic Research 1987;41(1):1217. Barton 1987 {published data only} Barton LL, Friedman AD. Impetigo: A reassessment of etiology and therapy. Pediatric Dermatology 1987;4:1858. Barton 1988 {published data only} Barton LL, Friedman AD, Portilla MG. Impetigo contagiosa: a comparison of erythromycin and dicloxacillin therapy. Pediatric Dermatology 1988;5:8891.
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Barton 1989 {published data only} Barton LL, Friedman AD, Sharkey AM, Schneller DJ, Swierkosz EM. Impetigo Contagiosa III. Comparative efcacy of oral erythromycin and topical mupirocin. Pediatric Dermatology 1989;6 (2):1348. Bass 1997 {published data only} Bass JW, Chan DS, Creamer KM, Thompson MW, Malone FJ, Becker TM, et al.Comparison of oral cephalexin, topical mupirocin, and topical bacitracin for treatment of impetigo. The Pediatric Infectious Disease Journal 1997;16:7089. Beitner 1996 {published data only} Beitner H. Cefadroxil compared with ucloxacillin for skin and soft tissue infection. Journal of Dermatological Treatment 1996;7(3): 1436. Blaszcyk 1998 {published and unpublished data} Blaszczyk-Kostanecka M, Dobozy A, Dominguez-SotoL, Guerrero R, Hunyadi J, Lopera J, et al.Comparison of two regimens of oral clindamycin versus dicloxacillin in the treatment of mild to moderate skin and soft-tissue infections. Current Therapeutic Research 1998;59(6):34153. Britton 1990 {published data only} Britton JW, Fajardo JE, Krafte-Jacobs B. Comparison of mupirocin and erythromycin in the treatment of impetigo. Journal of Pediatrics 1990;117:8279. Christensen 1994 {published data only} Christensen OB, Anehus S. Hydrogen peroxide cream: an alternative to topical antibiotics in the treatment of impetigo contagiosa. Acta Dermato- Venerologica 1994;74:4602. Dagan 1989 {published data only} Dagan R, Bar-David Y. Comparison of amoxicillin and clavulanic acid (Augmentin) for the treatment of nonbullous impetigo. American Journal of Diseases of Childhood 1989;143:9168. Dagan 1992 {published data only} Dagan R, Barr-David Y. Double-blind study comparing erythromycin and mupirocin for treatment of impetigo in children: implications of a high prevalence of erythromycin-resistant Staphylococcus aureus strains. Antimicrobial Agents and Chemotherapy 1992;36:28790. Daniel 1991a {published data only} Daniel R, European Azithromycin Study Group. Azithromycin, erythromycin and cloxacillin in the treatment of infections of skin and associated soft tissues. The Journal of International Medical Research 1991;19:43345. Daniel 1991b {published data only} Daniel R, European Azithromycin Study Group. Azithromycin, erythromycin and cloxacillin in the treatment of infections of skin and associated soft tissues. The Journal of International Medical Research 1991;19:43345. Demidovich 1990 {published data only} Demidovich CW, Wittler RR, Ruff ME, Bass JW, Browning WC. Impetigo: current etiology and comparison of penicillin, erythromycin, and cephalexin therapies. American Journal of Diseases of Childhood 1990;144:13135.
Dillon 1983 {published data only} Dillon HC. Treatment of staphylococcal skin infections: A comparison of cephalexin and dicloxacillin. Journal of the American Academy of Dermatology 1983;8(2):17781. Dux 1986 {published data only} Dux PH, Fields L, Pollock D. 2% topical mupirocin versus systemic erythromycin and cloxacillin in primary and secondary skin infections. Current Therapeutic Research 1986;40(5):93340. Eells 1986 {published data only} Eells LD, Mertz PM, Piovanetti Y, Pekoe GM, Eaglstein WH. Topical antibiotic treatment of impetigo with mupirocin. Archives of Dermatology 1986;122:12736. Esterly 1991 {published data only} Esterly NB, Markowitz M. The treatment of pyoderma in children. Journal of the American Medical Association 1970;212:66770. Fujita 1984 {published data only} Fujita K, Takahashi H, Hoshino M, Nonami E, Katsumata M, Miura Y, et al.Clinical evaluation of AT-2266 in the treatment of supercial suppurative skin and soft tissue infections. A double blind study in comparison with cephalexin compound granules (LKeex). Chemotherapy 1984;32:72853. Gilbert 1989 {published data only} Gilbert M. Topical 2% mupirocin versus 2% fusidic acid ointment in the treatment of primary and secondary skin infections. Journal of the American Academy of Dermatology 1989;20:10837. Ginsburg 1978 {published data only} Ginsburg CM, McCracken jr GH, Clahsen JC, Thomas ML. Clinical pharmacology of Cefadroxil in infants and children. Antimicrobial Agents and Chemotherapy 1978;13(5):8458. Goldfarb 1988 {published data only} Goldfarb J, Crenshaw D, OHoro J, Lemon E, Blumer JL. Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo. Antimicrobial Agents and Chemotherapy 1988;32(12):17803. Gonzalez 1989 {published data only} Gonzalez A. Schachner LA, Cleary T, Scott G, Taplin D, Lambert W. Pyoderma in childhood. Advances in Dermatology 1989;4: 12741. Gould 1984 {published data only} Gould JC, Smith JH, Moncur H. Mupirocin in general practice: a placebo-controlled trial. Royal Society of Medicine: International Congress and Symposium Series 1984;80:8593. Gratton 1987 {published data only} Gratton D. Topical mupirocin versus oral erythromycin in the treatment of primary and secondary skin infections. International Journal of Dermatology 1987;26(7):4723. Hains 1989 {published data only} Hains CS, Johnson SE, Nelson KG. Once-daily cefadroxil therapy for pyoderma. Pediatric Infectious Disease Journal 1989;8(9):6489. Jaffe 1985 {published data only} Jaffe AC, OBrien CA, Reed MD, Blumer, JL. Randomized comparative evaluation of Augmentin and cefaclor in pediatric skin and soft-tissue infections. Current Therapeutic ResearchClinical and Experimental 1985;38(1):1608.
21
Jaffe 1986 {published data only} Jaffe GV, Grimshaw JJ. A clinical trial of hydrocortisone/potassium hydroxyquinoline sulphate (Quinocort) in the treatment of infected eczema and impetigo in general practice. Pharmatherapeutica 1986; 4:62836. Kennedy 1985 {published data only} Kennedy CTC, Watts JA, Speller DCE. Mupirocin in the treatment of impetigo: a controlled trial against neomycin. In: Wilkinson DS, Price JD editor(s). Mupirocin - a novel topical antibiotic for the treatment of skin infection. Vol. 80, London: Royal Society of Medicine International Congress and Symposium Series, 1984: 7983. Kiani 1991 {published data only} Kiani R. Double-blind, double-dummy comparison of azithromycin and cephalexin in the treatment of skin and skin structure infections. European Journal of Clinical Microbiology and Infectious Diseases 1991;10:8804. Koning 2002 {published data only} Koning S, van Suijlekom-Smit LWA, Nouwen JL, Verduin CM, Bernsen RMD, Oranje AP, et al.Fusidic acid cream in the treatment of impetigo in general practice: a double blind randomised placebo controlled trial. BMJ 2002;324:20306. Koranyi 1976 {published data only} Koranyi KI, Burech DL, Haynes RE. Evaluation of bacitracin ointment in the treatment of impetigo. The Ohio State Medical Journal 1976;72(6):36870. McLinn 1988 {published data only} McLinn S. A bacteriologically controlled, randomized study comparing the efcacy of 2% mupirocin ointment (Bactroban) with oral erythromycin in the treatment of patients with impetigo. Journal of the American Academy of Dermatology 1990;22(5):8835. McLinn S. Topical mupirocin versus systemic erythromycin treatment for pyoderma. The Pediatric Infectious Disease Journal 1988;7(11):78590. Mertz 1989 {published data only} Mertz, PM. Comparison of the effects of topical mupirocin ointment to orally administered erythromycin in the treatment of impetigo in children. Journal of Investigative Dermatology 1987;88 (4):106973. Mertz PM, Marshall DA, Eaglstein WH, Piovanetti Y, Montalvo J. Topical mupirocin treatment of impetigo is equal to oral erythromycin therapy. Archives of Dermatology 1989;125:106973. Montero 1996 {published data only} Montero L. A comparative study of the efcacy, safety and tolerability of azithromycin and cefaclor in the treatment of children with acute skin and/or soft tissue infections. Journal of Antimicrobial Chemotherapy 1996;37(suppl C):12531. Moraes Barbosa 1986 {published data only} Moraes Barbosa AD. Comparative study between topical 2% sodium fusidate and oral association of chloramphenicol/neomycin/ bacitracin in the treatment of staphylococcic impetigo in new-born [Estudo comparativo entre o uso topico de fusidato de sodio a 2%, cloranfenicol, associacao neomicina/bacitracina e eritromicina (oral) no tratamento do impetigo estalococico do recemnascido]. Arquivos Brasileiros de Medicina 1986;60(6):50911.
Morley 1988 {published data only} Morley PAR, Munot LD. A comparison of sodium fusidate ointment and mupirocin ointment in supercial skin sepsis. Current Medical Research Opinion 1988;11:1428. Nolting 1988 {published data only} Nolting S, Strauss WB. Treatment of impetigo and ecthyma. A comparison of sulconazole with miconazole. International Journal of Dermatology 1988;27:7169. Park 1993 {published data only} Park SW, Wang HY, Sung HS. A study for the isolation of the causative organism, antimicrobial susceptibility tests and therapeutic aspects in patients with impetigo. Korean Journal of Dermatology 1993;31:3129. Pruksachat. 1993 {published data only} Pruksachatkunakorn C, Vaniyapongs T, Pruksakorn S. Impetigo: an assessment of etiology and appropriate therapy in infants and children. Journal of the Medical Association of Thailand 1993;76(4): 2229. Rice 1992 {published data only} Rice TD, Duggan AK, DeAngelis C. Cost-effectiveness of erythromycin versus mupirocin for the treatment of impetigo in children. Pediatrics 1992;89(2):2104. Rodriguez 1993 {published data only} Rodriguez-Solares A, Prez-Gutirrez F, Prosperi J, Milgram E, Martin A. A comparative study of the efcacy, safety and tolerance of azithromycin, dicloxacillin and ucloxacillin in the treatment of children with acute skin and skin-structure infections. Journal of Antimicrobial Chemotherapy 1993;31(suppl E):1039. Rojas 1985 {published data only} Rojas R, Eells L, Eaglstein W, Provanetti Y, Mertz PM, Mehlisch DR, et al.The efcacy of Bactroban ointment and its vehicle in the treatment of impetigo: a double-blind comparative study. Proceedings of an International Symposium, Nassau, Bahama Islands, 21-22 May 1984. 1985:96102. Rojas R, Zaias N. The efcacy of Bactroban ointment in the treatment of impetigo as compared to its vehicle: a double-blind comparative study. Proceedings of an International Symposium, Nassau, Bahama Islands, 21-22 May 1984. 1985:1504. Ruby 1973 {published data only} Ruby RJ, Nelson JD. The inuence of hexachlorophene scrubs on the response to placebo or penicillin therapy in impetigo. Pediatrics 1973;52:8549. Sutton 1992 {published data only} Sutton JB. Efcacy and acceptability of fusidic acid cream and mupirocin ointment in facial impetigo. Current Therapeutic Research 1992;51(5):6738. Tack 1997 {published data only} Tack KJ, Keyserling CH, McCarty J, Hedrick JA. Study of use of Cefdinir versus Cephalexin for treatment of skin infections in pediatric patients. Antimicrobial Agents and Chemotherapy 1997;41: 73942. Tack 1998 {published data only} Tack KJ, Littlejohn TW, Mailloux G, Wolf MM, Keyserling CH. Cefdinir adult skin infection study group. Cefdinir versus
22
cephalexin for the treatment of skin and skin-structure infections. Clinical Therapeutics 1998;20(2):24456. Tamayo 1991 {published data only} Tamayo L, Orozco MI, Sosa de Martinez MC. Topical rifamycin and mupirocin in the treatment of impetigo [Rifamycina SV y mupirocn tpicos en el tratamiento del imptigo]. Dermatologa Revista Mexicana 1991;55:99103. Tassler 1993 {published data only} Tassler H. Comparative efcacy and safety of oral eroxacin and amoxicillin/clavunalate potassium in skin and soft-tissue infections. The American Journal of Medicine 1993;94 Suppl 3A:159165. Vainer 1986 {published data only} Vainer G, Torbensen E. Treatment of impetigo in general practice: comparison of 3 locally administered antibiotics [Behandling af impetigo i almen praksis]. Ugeskrift for laeger 1986;148:12026. Wachs 1976 {published data only} Wachs GN, Maibach HI. Co-operative double-blind trial of an antibiotic / corticoid combination in impetiginized atopic dermatitis. British Journal of Dermatology 1976;95(3):3238. Wainscott 1985 {published data only} Wainscott G, Huskisson SC. A comparative study of Bactroban ointment and chlortetracycline cream. Proceedings of an International Symposium, Nassau, Bahama Islands, 21-22 May 1984. 1985:137140. Welsh 1987 {published data only} Welsh O, Saenz C. Topical mupirocin compared with oral ampicillin in the treatment of primary and secondary skin infections. Current Therapeutic Research 1987;41(1):11420. White 1989 {published data only} White DG, Collins PO, Rowsell RB. Topical antibiotics in the treatment of supercial skin infections in general practice - a comparison of mupirocin with sodium fusidate. Journal of Infection 1989;18:2219. Wilkinson 1988 {published data only} Wilkinson RD, Carey WD. Topical mupirocin versus topical neosporin in the treatment of cutaneous infections. International Journal of Dermatology 1988;27(7):5145.
study of SY 5555 versus cefaclor in the treatment of skin and skin structure infections. Chemotherapy 1994;42:74060. Arosemena 1977 {published data only} Arosemena R, Bogaert H, Bonilla Dib E, Close de Len J, Corrales H, Delgado Mayorga S, et al.Double blind study comparing preparations for topical application [Ensayo doble ciego entre preparaciones combinadas para aplicacin tpica]. Investigacin Mdica Internacional 1977;4:5028. Azimi 1999 {published data only} Azimi PH, Barson WJ, Janner D, Swanson R and the Unasyn Pediatric Study Group. Efcacy and safety of ampicillin/subactam and cefuroxime in the treatment of serious skin and skin structure infections in paediatric patients. The Pediatric Infectious Disease Journal 1999;18(7):60913. Baldwin 1981 {published data only} Baldwin RJT, Craneld R. A Multi-Centre General practice Trial Comparing Fucidin Ointment and Fucidin Cream. The British Journal of Clinical Practice 1981;35(4):15760. Ballantyne 1982 {published data only} Ballantyne F. Cefadroxil in the treatment of skin and soft-tissue infections. Journal of Antimicobial Chemotherapy 1982;10 Suppl B: 1437. Bastin 1982 {published data only} Bastin R, Rapin M, Kernbaum S. Controlled study of pristinamycin versus oxacillin in staphylococcal infections. Pathologie et Biologie 1982;30:4735. Bernard 1997 {published data only (unpublished sought but not used)} Bernard P, Vaillant L, Martin C, Beylot C, Quentin R, Touron D. Pristinamycin versus oxacillin in the treatment of supercial pyoderma [Pristinamycine (Pyostacine 500) versus Oxacilline (Bristopen) dans le traitement des pyodermites supercielles]. Annales de Dermatologie et de Venereologie 1997;124:3949. Bin Jaafar 1987 {published data only} bin Jaafar R, Pettit JHS, Gibson JR, Harvey SG, Marks P, Webster A. Trimethoprim-polymyxin B sulfate cream versus fusidic acid cream in the treatment of pyodermas. Pharmacology and Therapeutics 1987;26(1):603. Burnett 1963 {published data only} Burnett WJ. The route of antibiotic administration in supercial impetigo. The New England Journal of Medicine 1963;268:725. Cassels-Brown 1981 {published data only} Cassels-Brown G. A comparative study of fucidin ointment and cicatrin cream in the treatment of impetigo. The Brtitish Journal of Clinical Practice 1981;35(4):1535. Colin 1988 {published data only} Colin M, Avon P. Comparative double-blind evaluation of a new topical antibacterial [Evaluation comparative double aveugle du nouvel agent antibactrien topique, la mupirocine, par rapport un placebo dans le traitement des infections de la peau et des tussus mous]. Pharmatherapeutica 1988;5(198):198203. Cordero 1976 {published data only} Cordero A. Treatment of skin and soft-tissue infections with cefadroxil, a new oral cephalosporin. The Journal of International Medical Research 1976;4:1768.
23
References to studies excluded from this review

Alavena 1987 {published data only} Alavena R, Roitman J, Cuadros C. Contagious impetigo [Impetigo contagioso. Evulacion de siete esquemas de tratamiento]. Revista de la Sanida de las Fuerzas Policialis 1987;48(1):202. Anonymous 1998 {published data only} Anonymous. Cefdinir - A new oral Cephalosporin. The Medical Letter 1998;40(1034):857. Arata 1983 {published data only} Arata J, Nohara N, Suwaki M, Umemura S, Nakagawa S, Miyoshi K, et al.Double-blind comparative test of cefadroxil granules a longacting preparation of cephalexin. Japanese Journal of Antibiotics 1983;1443(36):144360. Arata 1994 {published data only} Arata J, Kanzaki H, Abe Y, Torigoe R, Ohkawara A, Yamanaka K, et al.A multicenter, double-blind, double-placebo comparative
Dillon 1970 {published data only} Dillon HC. The treatment of streptococcal skin infections. The Journal of Pediatrics 1970;76(5):67684. Dillon 1979 {published data only} Dillon HC, Gray BM, Ware JC. Clinical and laboratory studies with cefaclor: efcacy in skin and soft-tissue infections. Postgraduate Medical Journal 1979;55 Suppl 4:7781. Drehobl 1997 {published data only (unpublished sought but not used)} Drehobl M, Koenig L, Barker M, St-Clair P, Maladorno D. Fleroxacin 400 mg once daily versus ooxacin 400 mg twice daily in skin and soft-tissue infections. Chemotherapy 1997;43:37884. El Mofty 1990 {published data only} El Mofty M, Harvey SG, Gibson JR, Calthrop JG, Marks P. Trimethoprim-polymyxin B sulphate cream compared with fusidic acid cream in the treatment of supercial bacterial infection of the skin. The Journal of International Medical Research 1990;18:8993. Esterly 1970 {published data only} Esterly NB, Markowitz M. The Treatment of Pyoderma in Children. JAMA 1970;212(10):166770. Faingezicht 1992 {published data only} Faingezicht I, Bolanos HJ, Arias G, Guevara J, Ruiz M. Comparative study of cefprozil and cefaclor in children with bacterial infections of skin and skin structures. Pediatric Infectious Diseases Journal 1992;119:768. Fedorovskaya 1989 {published data only} Federovskaya RF, Bukharovich AM, Danilova TN, Masyukova SA, Blinova MY. Tomicide paste in combined therapy of pyoderma. Vestnik dermatologii i venerologii 1989;9:636. Fleisher 1983 {published data only} Fleisher GR, Wilmott CM, Campos JM. Amoxicillin combined with clavulanic acid for the treatment of soft-tissue infections in children. Antimicrobial Agents and Chemotherapy 1983;24(5): 67981. Forbes 1952 {published data only} Forbes MA. A clinical evaluation of neomycin in different bases. Southern Medical Journal 1952;45(3):2359. Golcman 1997 {published data only (unpublished sought but not used)} Golcman B, Tuma SR, Golcman R, Schalka S, Gonzalez MA. Efcacy and safety of cefprozil and cefaclor on cutaneous infections. Anais Brasileiros de Dermatologia 1997;72(1):7982. Goldfarb 1987 {published data only} Goldfarb J, Aronoff SC, Jaffe A, Reed MD, Blumer JL. Sultamicillin in the treatment of supercial skin and soft tissue infections in children. Antimicrobial Agents and Chemotherapy 1987;31:6634. Gooch 1991 {published data only} Gooch WM, Kaminester L, Cole GW, Binder R, Morman MR, Swinehart JM, et al.Clinical comparison of cefuroximhalexin and cefadroxil in the treatment of patients with primary infections of the skin or skin structures. Dermatologica 1991;18:33643. Haning 1992 {published data only} Haning MJ, Hausinger SA, Squires J. Loracarbef versus cefaclor in pediatric skin and skin structure infections. The Pediatric Infectious Disease Journal 1992;11 Suppl 8:2730.
Harding 1970 {published data only} Harding JW, Path MRC. Flucloxacillin in the treatment of skin and soft-tissue infections. The Practioner 1970;205:8016. Heskel 1992 {published data only} Heskel NS, Siepman NC, Pichotta PJ, Green E M, Stoll RW. Erythromycin versus cefadroxil in the treatment of skin infections. International Journal of Dermatology 1992;31(2):1313. Jacobs 1992 {published data only} Jacobs RF, Brown WD, Chartrand S, Darden P, Drehobl MA, Yetman R, et al.Evaluation of cefuroxime axetil and cefadroxil suspensions for treatment of pediatric skin infections. Antimicrobial Agents and Chemotherapy 1992;36:16148. Jennings 1999 {published data only} Jennings MB, Aleri D, Kosinski M, Weinberg JM. An investigator-blind study of the efcacy and safety of azithromycin versus cefadroxil in the treatment of skin and skin structure infections of the foot. The Foot: International Journal of Clinical Foot Science 1999;9(2):6872. Keeny 1979 {published data only} Keeney RE, Seamans ML, Russo RM, Gururaj VJ, Alle JE. The comparative efcacy of minocycline and penicillin-V in Staphylococcus aureus skin and soft-tissue infections. Therapeutics for the Clinician 1979;23:7118. Kumakiri 1988 {published data only} Kumakiri M, Yasui C, Ohkawara A. Clinical study on TE-031 tablet in dermatology. Chemotherapy 1988;36:9357. Kumar 1988 {published data only} Kumar A, Murray DL, Hanna CB, Kreindler TG, Jacobson KD, McCall Bundy J, et al.Comparitive study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft-tissue infections. Antimicrobial Agents and Chemotherapy 1988;32(6):8825. Lassus 1990 {published data only} Lassus A. Comparative studies of azithromycin in skin and softtissue infections and sexually transmitted infections by Neisseria and Chlamydia species. The British Society for Antimicrobial Chemotherapy 1990;25(A):11521. Lentino 1984 {published data only} Lentino JR, Stachowski M, Strikas R, Parrillo P. Comparative efcacy of cefotiam versus cephalotin in the therapy of skin and soft-tissue infections. Antimicrobial Agents and Chemotherapy 1984; 25(6):77880. Levenstein 1982 {published data only} Levenstein JH. Efcacy and tolerability of an amoxycillin/ clavulanic acid combination in the treatment of common bacterial infections. Sa Mediese tydskrif 1982;62:1620. Lewis 1985 {published data only} Lewis-Jones S, Hart CA, Vickers CFH. Bactroban ointment versus fusidic acid in acute primary skin infections in children. Excerpta Medica Current Clinical Practice Series 1985;16:1038. Linder 1993 {published data only} Linder CW, Nelson K, Paryani S, Stallworth JR, Blumer JL. Comparative evaluation of cefadroxil and cephalexin in children and adolescents with pyodermas. Clinical Therapeutics 1993;15: 4656.
24
Lipets 1987 {published data only} Lipets ME, Gnidenko VV. Gentamycin ointment in the therapy of impetigo in children [Article in Russian]. Pediatriia 1987;9:103. MacKenna 1945 {published data only} MacKenna RMB, Cooper-Willis ES. Impetigo contagiosa in the army, treated with microcrystalline sulphathiazole. The Lancet 1945;22:639. Macotela-Ruiz 1988 {published data only (unpublished sought but not used)} Macotela-Ruiz E, Duran-Bermudez H, Kuri-Con FJ, ArevaloLopez A, Villalobos-Ibarra JL. Evaluation of the efcacy and toxicity of local fusidic aid versus oral dicloxacillin in infections of the skin [Evaluacion de la ecacia y toxicidad del acido fusidico local frente a dicloxacilina oral en infecciones de la piel]. Medicina cutanea ibero-latino-americana 1988;16:1713. Mallory 1991 {published data only} Mallory SB. Azithromycin compared with cephalexin in the treatment of skin and skin structure infections. American Journal of Medicine 1991;91 Suppl 3A:369. McCarty 1992 {published data only} McCarty J, Ruoff GE, Jacobson KD. Loracarbef (LY163892) versus cefaclor in the treatment of bacterial skin and skin structure infections in an adult population. The American Journal of Medicine 1992;92 Suppl 6A:805. McMillan 1969 {published data only} McMillan R, Hurwitz R. Tropical bacterial pyoderma in Vietnam. JAMA 1969;210(9):17346. Milidi d Silva 1985 {published data only} Milidi da Silva I, Silva SCL. The evaluation of Bactroban ointment in the treatment of dermatological infections. Proceedings of an International Symposium, Nassau, Bahama Islands, 21-22 May 1984. 1985:1625. Nakayama 1983 {published data only} Nakayama I, Akieda Y, Watanabe T, Suzuki T, Itokawa K. Clinical investigation of a long-acting amoxicillin preparation in patients with skin and soft-tissue infections in surgery. The Japanese Journal of Antibiotics 1983;36(5):113763. Neldner 1991 {published data only} Neldner KH. Double-blind randomized study of oral temaoxacin and cefadroxil in patients with mild to moderately severe bacterial skin infections. The American Journal of Medicine 1991;91 Suppl 6A:1114. Nichols 1997 {published data only} Nichols RL, Smith JW, Gentry LO, Gezon J, Campbell T, Sokol P, et al.Multicenter, randomized study comparing levooxacin and ciprooxacin for uncomplicated skin and skin structure infections. Southern Medical Journal 1997;90(12):1193200. Nicolle 1990 {published data only} Nicolle LE, Postl B, Urias B, Ling N, Law B. Outcome following therapy of group A streptococcal infection in schoolchildren in isolated northern communities. Canadian Journal of Public Health 1990;81:46870. Nolting 1992 {published data only} Nolting S, Brutigam M. Clinical relevance of the antibacterial activity of terbinane: a contrallateral comparison between 1%
terbinane cream and 0.1% gentamicin sulphate cream in pyoderma. British Journal of Dermatology 1992;126(39):5660. Orecchio 1986 {published data only} Orecchio RM, Mischler TW. A double-blind multiclinic comparative trial of mupirocin topical and its vehicle in the treatment of bacterial skin infections. Current Therapeutic Research 1986;39(1):826. Palazzini 1993 {published data only} Palazzini E, Palmerio B. Treatment of pyogenic skin infections with rifaximin cream. European Review for Medical and Pharmacological Sciences 1993;15:8792. Parish 1984 {published data only} Parish LC, Aten EM. Treatment of skin and skin structure infections: a comparative study of augmentin and cefaclor. Therapeutics for the Clinician 1984;34:56770. Parish 1991 {published data only} Parish LC, Jungkind DL. Systemic antimicrobial therapy in skin and skin structure infections: comparison of temaoxacin and ciprooxacin. The American Journal of Medicine 1991;91 Suppl 6A:115119. Parish 1997 {published data only} Parish LC, Doyle CA, Durham SJ, Wilber RB. Cefprozil versus cefaclor in the treatment of mild to moderated skin and skinstructure infections [Cefprozil versus cefaclor no tratamento de infeccoes leves a moderadas da pele e estruturas da pele]. Revista brasileira de medicina 1997;54(5):3428. Pien 1983 {published data only} Pien FD. Double-blind comparative study of two-dosage regimens of cefaclor and amoxicillin-clavulanic acid in the outpatient treatment of soft-tissue infections. Antimicrobial Agents and Chemotherapy 1983;24(6):8569. Powers 1991 {published data only} Powers RD, Schwartz R, Snow RM, Yarbrough III DR. Ooxacin versus cephalexin in the treatment of skin, skin structure, and softtissue infections in adults. Clinical Therapeutics 1991;13(6): 72736. Powers 1993 {published data only} Power RD. Open trial of oral eroxacin versus amoxicillin/ clavulanate in the treatment of infections of skin and soft tissue. The American Journal of Medicine 1993;94 Suppl:1558. Puspenogoro 1990 {published data only} Pusponegora EHD, Wiryadi BE. Clindamycin and cloxacillin compared in the treatment of skin and soft-tissue infections. Clinical Therapeutics 1990;12(3):23641. Risser 1985 {published data only} Risser WL, Kaplan, et al.Treatment of soft-tissue infections in children with amoxicillin-clavulanic combination or cefaclor. Current Therapeutic Research-Clinical and Experimental 1985;37(4): 74753. Saenz 1985 {published data only} Saenz C, Garcia-Estrada E. Controlled clinical trial of Bactroban ointment in the treatment of skin infections. Excerpta Medica Current Clinical Practice Series 1985;16:20510.
25
Salzberg 1972 {published data only} Salzberg R. Comparative clinical and bacteriological studies with Bactrim and ampicillin in the pediatrics [Vergleichende klinische und bakteriologische Untersuchungen mit Bactrim und Ampicillin in der pdiatrischen Praxis]. Schweizerische Rundschau fur Medizin Praxis / Revue suisse de medecine Praxis 1972;61(33):10512. Schupbach 1992 {published data only} Schupbach CW, Olovich KG, Dere WH. Efcacy of cefaclor AF in the treatment of skin and skin structure infections. Clinical Therapeutics 1992;14(3):4709. Schwartz 1996 {published data only} Schwartz R, Das-Young LR, Ramirez-Ronda C, Frank E. Current and future management of serious skin and skin-structure infections. The American Journal of Medicine 1996;100 Suppl 6A: 915. Smith 1985 {published data only} Smith JH, Gould JC. Placebo-controlled study of Bactroban ointment in patients attending general practice. Proceedings of an International Symposium, Nassau, Bahama Islands, 22-24 May 1984. 1985:1306. Smith 1993 {published data only} Smith JW, Nichols RL. Comparison of oral eroxacin with oral amoxicillin/clavulanate for treatment of skin and soft-tissue infections. The American Journal of Medicine 1993;94:1504. Sobye 1966 {published data only} Sobye P. Cutaneous Staphylococcus aureus infection treated with fucidin ointment [Kutane Staphylococcus aureus infektioner behandlet med fugidinsalve]. Ugeskrift for Laeger 1966;128(7): 2047. Stevens 1993 {published data only} Stevens DL, Pien F, Drehobl M. Comparison of oral cefpodoxime proxetil and cefaclor in the treatment of skin and soft-tissue infections. Diagnostic Microbiology & Infectious Disease 1993;16: 11329. Tack 1991 {published data only} Tack KJ, Wilks NE, Sermdikian G, Frazier CH, Shirin K, Puoipolo A, et al.Cefpodoxime proxetil in the treatment of skin and softtissue infections. Drugs 1991;42:516. Urbach 1966 {published data only} Urbach F. Combined chemotherapy in the treatment of supercial bacterial infections of the skin. Current Therapeutic Research 1966;8 (4):199202. Villiger 1986 {published data only} Villiger JW, Robertson WD, Kanki K, Ah Chan M, Fetherston J, Hague IK, et al.A comparison of the new topical antibiotic mupirocin (Bactroban) with oral antibiotics in the treatment of skin infections in general practice. Current Medical Research and Opinion 1986;10(5):33945. Wachs 1992 {published data only} Wachs GN, Nolen TM, Parish LC, Morman MR, Cleaver L, Ginsberg D. Comparison of cefadroxil and amoxicillin/clavulanate in mild to moderate skin and skin-structure infections. Advances in Therapy 1992;9(2):6980. Wolbling 1987 {published data only} Wlbling RH, Schfer V. Treatment of impetiginized eczema with prednicarbate in combination with a quarternary ammonium salt
[Zur Behandlung des impetiginisierten Ekzems mit Prednicarbat in Kombination mit einem quarternren Ammoniumsalz]. Arzneimittelforschung 1987;37(2):21820. Wong 1989 {published data only} Wong KS, Lim KB, Tham SN, Ling ML, Tan T. Comparative double-blinded study between mupirocin and tetracycline ointments for treating skin infections. Singapore Medical Journal 1989;30:3803. Yura 1988 {published data only} Yura J, Shinagawa N, Mizuno A, Watanabe S, Ando M, Sakai K, et al.Clinical evaluation of cefpodoxime proxetil in the treatment of skin and soft-tissue infections. The Japanese Journal of Antibiotics 1988;41(10):151737.
References to studies awaiting assessment

Ciftci 2002 {published data only} Ciftci E, Guriz H, Aysev AD. Mupirocin vs terbinane in impetigo. Indian Journal of Pediatrics 2002;29(9):67982. [MEDLINE: 12356219] Claudy 2001 {published data only} Claudy A, Groupe Francais dEtude. Supercial pyoderma requiring oral antibiotic therapy [Pyodermites supercielles necessitant une antibiotitherapie orale. Acide fusidique versus pristinamycine]. La Presse Medicale 2001;30(8):3648. Liu 1986 {published data only} Liu ZL, Jiang ZP. Comparison between the curative effect of traditional Chinese medicine and Western medicine in child impetigo herpetiformis. Chinese Journal of Integrated Traditional and Western Medicine 1986;6(9):5666. Parish 2000 {published data only} Parish LC, Routh HB, Miskin B, Fidelholtz J, Werschler P, Heyd A, et al.Moxioxacin versus cephalexin in the treatment of uncomplicated skin infections. International Journal of Clinical Practice 2000;54(8):497503.
References to ongoing studies

McLinn 1988b {published data only} McLinn S. A bacteriologically controlled, randomized study comparing the efcacy of 2% mupirocin ointment (Bactroban) with oral erythromycin in the treatment of patients with impetigo. Journal of the American Academy of Dermatology 1990;22(5):8835.
Additional references
Baltimore 1985 Baltimore RS. Treatment of impetigo: a review. Pediatric Infectious Diseases 1985;4:597601. Boukes 1999 Boukes FS, van der Burgh JJ, Nijman FC, Sampers GM, Simon B, Romeynders AC, et al.Dutch College of General Practitioners guideline Bacterial skin infections [NHGStandaard bacterile huidinfecties]. Huisarts Wet 1999;41:42737. Britton 1990 Britton JW, Fajrdo JE, Krafte-Jacobs B. Comparison of mupirocin and erythromycin in the treatment of impetigo. Journal of Pediatrics 1990;117:8279.
26
Bruijnzeels 1993 Bruijnzeels MA, van Suijlekom-Smit LWA, van der Velden J, van der Wouden JC. [Het kind bij de huisarts.]. The child in general practice. Dutch National Survey of morbidity and interventions in general practice. Rotterdam: Erasmus University Rotterdam, 1993. Canizares 1993 Canizares O. Epidemiology and ecology of skin diseases in the tropics and subtropics. In: Canizares O editor(s). A manual of dermatology for developing countries. 2nd Edition. Oxford: Oxford University Press, 1993:2235. Carruthers 1988 Carruthers R. Prescribing antibiotics for impetigo. Drugs 1988;36: 3649. Dagan 1992 Dagan R, Barr-David Y. Double blind study comparing erythromycin and mupirocin for treatment of impetigo in children: implications of a high prevalence of erythromycin-resistant Staphylococcus Aureus strains. Antimicrobial agents and chemotherapy 1992;36:28790. Dagan 1993 Dagan R. Impetigo in childhood: changing epidemiology and new treatments. Pediatric annals 1993;22:23540. de Neeling 1998 de Neeling AJ, van Leeuwen WJ, Schouls LM, et al.Resistance of staphylococci in the Netherlands: Surveillance by an electronic network during 1989-1995. Journal of Antimicrobial Chemotherapy 1998;41:93101. Dillon 1979 Dillon HC. Post-streptococcal glomerulonephritis following pyoderma. Review of Infectious Diseases 1979;1:93543. Espersen 1998 Espersen F. Resistance to antibiotics used in dermatological practice. British Journal of Dermatology 1998;139:48. Hay 1998 Hay RJ, Adriaans BM. Bacterial infections. In: Champion RH Burton JL, Ebling FJG editor(s). Textbook of Dermatology. 6th Edition. Oxford: Blackwell, 1998:110911. Jadad 1996 Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al.Assessing the quality of reports of randomized
clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17:112. Jadad 1998 Jadad AR, Moher D, Klassen TP. Guides for reading and interpreting systematic reviews: II How did the authors nd the studies and assess their quality?. Archives of Paediatrics and Adolescent Medicine 1998;152:8127. Kristensen 1991 Kristensen JK. Scabies and pyoderma in Lilongwe, Malawi: Prevalence and seasonal uctuation. International Journal of Dermatology 1991;30:699702. MacKenna MacKenna RMD, Cooper-Willis ES. Impetigo in the army, treated with microcrystalline sulphathiazole. Lancet 1945;269:3578. McCormick 1995 McCormick A, Fleming D, Charlton J. Morbidity statistics from general practice. Fourth national study 1991-1992. London: HMSO, 1995. Resnick 2000 Resnick DS. Staphylococcal and streptococcal skin infections: pyodermas and toxin-mediated syndromes.. In: Harper J, Oranje A, Prose N editor(s). Textbook of Pediatric Dermatology. 1st Edition. Oxford: Blackwell Science, 2000:36972. Ruby 1973 Ruby RJ, Nelson JD. The inuence of hexachlorophene scrubs on the response to placebo or penicillin therapy in impetigo. Pediatrics 1973;52:8549. Smeenk 1999 Smeenk G, Sebens FW, Houwing RH. Use and disadvantages of local antibiotics and disinfectants on the skin [Nut en gevaren van op de huid toegepaste antibiotica en desinfectantia]. Ned Tijdschr Geneesk 1999;143:11403. Verhagen 1998 Verhagen AP, de Vet HCW, de Bie RA, Kessels AG, Boers M, Bouter LM, at al. The Delphi list: a criteria list for quality assessment of randomised clinical trials for conducting systematic reviews developed by Delphi consensus. Journal of Clinical Epidemiology 1998;12:123541. Indicates the major publication for the study
27
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Arata 1989a Methods time NR Japan Range (13/265) Age 15 to 82 yrs, M/F 150/115 (all participants) mainly S.aureus cefdinir 100 mg, 3 td cefaclor 250 mg, 3 td Ten days, excellent/good/poor SE: (all participants) cefdinir 9/142 cefaclor 4/145 (mainly gastrointestinal)
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Arata 1989b Methods time NR Japan Range (18/259) All ages, M/F 152/97 mainly S.aureus (data for all participants) lomeoxacin 200 mg, 3 td noroxacin 200 mg, 3 td seven days, cured/improved SE: (all participants) L 6/144, N 5/135 mainly gastrointestinal Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
28
Arata 1989b
(Continued)
Risk of bias Item Allocation concealment? Arredondo 1987 Methods time NR Mexico city, Mexico Range (55/61) average age seven yrs, M/F 30/31 S.aureus 67% mupirocin ointment 2%, 3 td, 5 to 10 days dicloxacillin 250 mg, 4 td, 5 to 10 days Ten days, cure open trial. LTFU 2/55 (1 in both groups) SE: M: nil reported D: abdominal pain 1/ 31, vomiting 2/31 Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Authors judgement No Description C - Inadequate
Barton 1987 Methods 1986 June to August Missouri USA outpatients only impetigo Children (age NR), M/F 29/32 S.aureus 35/65 Streptococcus 2/65 Both 30% PE penicillin V 50 mg/kg/day in 4 dd, 10 ds erythromycin 40 mg/kg/day in 4 dd, 10 ds
29
Participants
Interventions
Barton 1987
(Continued)
Outcomes Notes
Seven days, failure LTFU 6/35 (not evaluable) SE: NR
Risk of bias Item Allocation concealment? Authors judgement Yes Description A - Adequate
Barton 1988 Methods 1987 June to August Missouri USA outpatients only impetigo 2 m to 16 yrs, M/F 55/45 S. aureus 46/100, S. pyogenes 9/100, both 25/199. PE erythromycin 40 mg/kg/day in 4 dd, 10 ds dicloxacillin 25 mg/kg /day in 4 dd, 10 ds Five to seven days, cure+improved LTFU: of 100 included, 12 lost, 8 non compliant, 59 evaluable (only participants with S. aureus were analysed) SE: abdominal pain: E 1, D 1 vomiting+rash: E 0, D 1
Participants
Interventions
Outcomes Notes
30
Barton 1989 Methods 1988 June to August Missouri USA outpatients only impetigo 3 m to 16 yrs M/F 49/48 S. aureus 80% PNE erythromycin 40 mg/kg/day in 3 dd, 7 days mupirocin ointment 2%, 3 td, 7 days Four to seven days, cured + improved LTFU: 1/97 non-bullous and 14% bullous SE: gastrointestinal: E 8/48, M 4/49
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Bass 1997 Methods time NR Honolulu, Hawaii Hospital outpatients only impetigo average age 3.8 yrs, sex NR S. aureus 41/48 PNE Three arms: -cephalexin 50 mg/kg/day in 3 dd + placebo ointment, 10 days -mupirocin ointment 2%, 3 td + liquid oral placebo -bacitracin ointment 500 units/g, 3 td + liquid oral placebo Eight to ten days, cure LTFU 6/32, 5 in mupirocin group SE: not reported Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias
Bass 1997
(Continued)
Item Allocation concealment? Beitner 1996 Methods
Authors judgement Unclear
Description B - Unclear
Dec 1992 to Nov 1994 25 centres, Sweden outpatients Range (60/327) Age range 3 to 80 yrs S. aureus 86% of 327, Streptococcus 14% of 327 PE. Included only participants who had bacteria sensitive to both drugs cefradoxil 40 mg/kg/day, 10 days ucloxacillin tablets 750 mg, 2 td, or susp 30 to 50 mg/kg/day in 2 to 3 dd, 10 days 10 to 12 days, cure/improved/failed evaluable 327/661 (all participants) SE: diarrhoea C 14/327 (all pat.), F 87/324 Severe: (stomach ache/rash/fever/ vomiting) C 14/327, F 2/234 (all participants)
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Blaszcyk 1998 Methods 1996 to 1997? Multicenter; Europe, Latin America and Asia. Range (42/539) 16 to 70 yrs (all participants) PNE clindamycin caps 150 mg, 4 td clindamycin caps 300 mg, 2 td dicloxacillin caps 250 mg, 4 td Seven days, cure Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes
32
Blaszcyk 1998
(Continued)
Notes
LTFU: 8.8% (all participants) SE: (all participants) clin 150 19%, clin 300 17%, diclox 10%
Risk of bias Item Allocation concealment? Britton 1990 Methods Oct 1988 to Oct 1989 Portsmouth Virginia USA outpatients only impetigo 2 months to 12 yrs, M/F 27/17 S. aureus 26/48 PNE erythromycin 40 mg/kg/day in 4 dd + placebo cream mupirocin ointment 2%, 3 td + placebo susp. Ten days, cured + improved LTFU: E: 4/30, M: 2/24 SE minor gastrointestinal SE: 11 total, equally divided Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Christensen 1994 Methods time NR Sweden, Germany, UK Outpatients (Germany) and GP (UK), both (Sweden) only impetigo 3 + yrs. M/F131/125 S.aureus 199/256, S.pyogenes 21/256, both 36/256
33
Participants
Christensen 1994
(Continued)
PE Interventions Hydrogen peroxide cream 1% (Microcid), 2 to 3 td, max. 21 days Fusidic acid cream gel 2%, 2 to 3 td, max 21 days evaluation time NR, cure LTFU: NR SE: (led to withdrawal)skin irritation 1 burning, 1 blistering 1 (all FA) Hydrogen peroxide: 0. Mild SE: FA 9, Hydrogen peroxide: 13
Outcomes Notes
Dagan 1989 Methods May to October 1987 Negev region, Israel Outpatients only impetigo 6 m to 9 yrs, sex NR S. aureus 37/51, S. pyogenes 14/51 PE amoxicillin trihydrate syrup 40 mg/kg/day, in 3 dd, 10 days amoxicillin/clavulanic acid syrup, 40 + 10 mg/kg/day, in 3 dd, 10 days Five days, cure +improved 4/26 (amox) and 3/25 (amox/clav) participants missing from data of rst follow-up moment SE: vomiting amox 1 amox/clav 0 diarrhoea amox 1 amox/clav 0
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Authors judgement Unclear Description D - Not used
34
Dagan 1992 Methods July 1989 to Oct 1990 Negev region, Israel outpatients only impetigo (bullous and non-bullous) < 16 yrs, M/F 56/46 S. aureus 90/102, streptococci 1/3 of participants PNE erythromycin susp. 50 mg/kg/day 3td + placebo ointment, 7 days mupirocin ointment 2% 3td + oral placebo susp., 7 days Seven days, failed LTFU 8/51 E, 5/51 M SE: gastrointestinal E 11/47 M 4/51
Participants
Interventions
Outcomes Notes
Daniel 1991a Methods 1987 to 1991 Belgium/France/FRG/ Netherlands/Norway/UK setting unclear Range (69/308) 16 to 80 yrs All participants: S. aureus 195/308, streptococci 59/308 PNE azithromycin 250 mg twice (day 1),once daily (day 2 to 5), 5 days erythromycin 500 mg 4 td, 7 days 11 to 16 days, cured LTFU:azithromycin 1/36 erythromycin 2/33 SE: no subgroup data
Participants
Interventions
Outcomes Notes
35
Daniel 1991a
(Continued)
Risk of bias Item Allocation concealment? Daniel 1991b Methods 1987-1989 Belgium/Germany/Ireland/UK setting unclear Range (17/323) adults 17 to 90 yrs All participants: S aureus 158/323, streptococci 41/323 PNE azithromycin 250 mg twice (day 1),once daily (day 2 to 5), 5 days cloxacillin 500 mg, 4 td, 7 days 11 to 16 days, cured/improved/failed LTFU azithromycin 0/10 cloxacillin 1/7 SE: no subgroup data Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Demidovich 1990 Methods time NR Honolulu, Hawaii outpatients only impetigo 5 m to 15 yrs. average 3 yrs S. aureus 45/73, GABHS 6/73, both 14/73, PNE Authors judgement Unclear Description B - Unclear
Participants
36
Demidovich 1990
(Continued)
Interventions
penicillin V 40 to 50 mg/kg/day in 3 dd, 10 days cephalexin 40 to 50 mg/kg/day in 3 dd, 10 days erythromycin 30 to 40 mg/kg/day in 3 dd, 10 days Eight to ten days, failed LTFU: 2 of 75 not available for follow-up SE: nil reported
Outcomes Notes
Risk of bias Item Allocation concealment? Dillon 1983 Methods 1980 summer/fall Alabama/USA outpatients only impetigo (bullous impetigo 57/70) average age 3.2 yrs, MF 41/37 S. aureus: 64/70 PNE cephalexin 50 mg/kg/day in 2 dd (> 20 kg: 500 mg 2 td) dicloxacillin 15 mg/kg/day in 4 dd (> 40 kg: 125 mg 4 td) Prompt cure LTFU: C: 5/40, D: 3/38 Bullous impetigo SE: NR Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Authors judgement Unclear Description B - Unclear
37
Dux 1986 Methods time NR Toronto, Canada setting unclear Range (36/149) average age 22 yrs. M/F 81/68 bacterial culture results unclear PNE mupirocin ointment 2%, 3 td, 7 days eythromycin 250 mg, 4 td, 7 days cloxacillin 250 mg, 4 td, 7 days Seven days, cure/improved/failure: C no participants with impetigo allocated Two cases of secondary impetigo, both in mupirocin group, excluded from results presented here SE: M: pruritus 1/78. E: nausea and abdominal pain 1/50, Cloxacillin: none/20 (all participants
Participants
Interventions
Outcomes
Notes
Eells 1986 Methods Oct to Nov 1983 Puerto Rico outpatients only impetigo 7 m to 13 yrs, M/F 13/25 mainly S.aureus PE mupirocin ointment 2%, 3 td, 7 to 9 days vehicle control, 3 td, 7 to 9 days Eight days, cure/improved/failure: (one participant with ecthyma excluded in each group) LTFU: M: 8/26, V: 6/26 SE: NR
Participants
Interventions
Outcomes
Notes
Risk of bias
Eells 1986
(Continued)
Item Allocation concealment? Esterly 1991 Methods
time NR Milwaukee Wisconsin USA outpatients only impetigo 3 m to 14 yrs, average 4.3 yrs S.aureus 33% GABHS 12% both 41%. Part excluded: NR mupirocin (dose NR) erythromycin (dose NR) time of evaluation NR, failure LTFU: M:3/25, E: 3/23 SE: M: nil reported, E: stomach pain and nausea 1/20, vomiting and irritability 1/20, hysterical attacks 1/20
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Fujita 1984 Methods time NR Japan outpatients Range (10/204) Age 16 to 84 yrs M/F 120/84 (all participants) enoxacin 500 mg, 3 td cephalexin 500 mg 2 td (double dummy) Authors judgement Unclear Description B - Unclear
Participants
Interventions
39
Fujita 1984
(Continued)
Outcomes Notes
after ... cured/improved LTFU 20/224 SE (all participants): E 11 of 113, C 4 of 110 (mainly gastrointestinal) Secondary impetigo
Risk of bias Item Allocation concealment? Gilbert 1989 Methods time NR Quebec Canada outpatients Range (19/70) Age NR S. aureus 41/70 Streptococci 22/70 (all pat.) PE mupirocin ointment 2%, 3 td, 7 days fusidic acid cream 2%, 3 td, 7 days Seven days, cure/improved/failure LTFU: nil in impetigo groups SE nil recorded in either group Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Ginsburg 1978 Methods time NR Dallas, Texas, USA outpatients only impetigo Authors judgement Unclear Description B - Unclear
40
Ginsburg 1978
(Continued)
Participants
8 m to 8 yrs, average 3.1 yrs, sex NR S.aureus 78%, GABHS 64%, both 50%. Part excluded: unclear penicillin G 30 mg/kg/day in 4 dd, duration NR cefadroxil 45 mg/kg/day in 3 dd, duration NR Eight days, cured + improved LTFU 21/71 SE: one child removed from cefadroxil group because of vomiting, no other SE reported
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Goldfarb 1988 Methods time NR Cleveland Ohio USA outpatients only impetigo 5 m to 13 yrs, average 3.8. M/F 31/31 S.aureus 49/62, Streptococci 4/62, Both 9/62 Part. excluded:NR mupirocin ointment 2%, 3 td, 8 days erythromycin 40 mg/kg/day in 4 dd, 8 days Eight days, cured/failed LTFU M 1/30, E 3/32 SE: M 0/30, E: 5/30 mild diarrhoea Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias
41
Goldfarb 1988
(Continued)
Item Allocation concealment? Gonzalez 1989 Methods
1980 July to Sept Florida USA outpatients only impetigo (bullous and non-bullous). 6 m to 12 yrs participants excluded if no S. aureus present penicillin V Potassium 50 mg/kg/day, in 4 dd, 10 days cloxacillin sodium 50 mg/kg/day, in 4 dd, 10 days Ten days: cured + improved LTFU: P 1/44, C 10/43 SE: NR
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Gould 1984 Methods time NR Edinburgh UK general practice Range (39/107) Average age 18.7 (all participants) S. aureus 90/129, streptococci 32/129 (all participants) PNE mupirocin ointment 2%, once daily, until cleared placebo cream, once daily, until cleared time of evaluation NR cure/improved/failure LTFU M 3/17, P 1/22 SE NR
42
Participants
Interventions
Outcomes
Notes
Gould 1984
(Continued)
Risk of bias Item Allocation concealment? Gratton 1987 Methods time NR Montreal Quebec Canada outpatients Range (15/60) Age/sex NR S. aureus approx. 50% Part. excluded: NR mupirocin ointment 2%, 3 td, 7 days erythromycin 250 mg, 4 td, 7 days Seven days, cure/improved/failure SE not presented for impetigo patients Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes Risk of bias Item Allocation concealment? Hains 1989 Methods
1986 summer Birmingham Alabama US outpatients child hospital only impetigo 1 to 18 yrs, sex NR S. aureus 35%, GABHS 12% both 54% part. excluded: NR cefadroxil 30 mg/kg/day, max 1 g., in 1 dd, 10 days cephalexin 30 mg/kg/day, max 1 g., in 2 dd, 10 days 14 days, cured SE: nil reported
43
Participants
Interventions
Outcomes Notes
Hains 1989
(Continued)
Risk of bias Item Allocation concealment? Jaffe 1985 Methods time NR Cleveland Ohio USA outpatients child clinic Range (32/42) 6 m to 12 yrs, ave to age 4.8 yrs S. aureus 33/36, S. pyogenes 8/36 PNE amoxicillin/clavulanic acid, eq. 20 mg/kg/day in 3 dd, 10 days cefaclor 20 mg/kg/day in 3 dd. Ten days, cured/failed SE: mild diarrhoea: A/C 2/18, C 5/16 (all participants) Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Jaffe 1986 Methods time NR Multicenter, Wessex UK general practice Range (43/119) 2,5 yrs to 83 yrs, median 14 to 16 yrs M/F 23/20. S. aureus 16/34, S. pyogenes 5/34. PNE 1% hydrocortisone + 0.5% potassium hydroxyquinoline sulphate cream, 2 td, 14 days 1% hydrocortisone + 2% miconazole nitrate cream, 2 td, 14 days
44
Participants
Interventions
Jaffe 1986
(Continued)
Outcomes Notes
Seven days, cured/improved SE: mild staining HC + h 2/24 HC + m 0/24
Risk of bias Item Allocation concealment? Kennedy 1985 Methods time NR Bristol UK general practice only impetigo average age 11 yrs (mupirocin), 17 yrs (Neomycin). M/F 2/1. S. aureus 23/34, S. pyogenes 10/34. PNE mupirocin ointment 2%, 2 td, 10 to 11 days neomycin ointment 1%, 2 td, 10 to 11 days time of evaluation NR cure/improved/failure LTFU mupi 0/15, Neomycin 1/18 SE nil reported Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes
Notes
45
Kiani 1991 Methods time NR multicentre USA (Southern States) admitted + outpatients Range (18/179) Age > 16, . 211/154 (all participants) S. aureus 152/179, S. pyogones 29/179 (all patients) PE azithromycin 500 mg day 1, 250 mg, day 2 to 5, 5 days cephalexin 500 mg twice daily, 10 days 11 days, cured/improved 253 entered, 41 LTFU, 21 resistant pathogen, 12 excluded for other reasons 179 evaluable SE: no subgroup data
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Koning 2002 Methods 1999 Feb to 2000 Nov Rotterdam, Netherlands general practice only impetigo < 12, average age 5.0 yrs. M/F 98/62 S. aureus 127/160, S. pyogenes 5/160, both 8/160, none 20/160 PNE fusidic acid cream 2%, 3 td + povidone-iodine shampoo, 2 td placebo cream, 3 td + povidone-iodine shampoo, 2 td Seven days, cure LTFU: 4/160 (2 in each group) SE: FA 7/76, P 19/80 (mainly pain and burning by povidone-iodine) Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias
Koning 2002
(Continued)
Item Allocation concealment?
Authors judgement Yes
Description A - Adequate
Koranyi 1976 Methods 1974 Columbus, Ohio, USA outpatients only impetigo 2 m to 15 yrs. M/F 14/16. S. aureus 22/30, S. pyogenes 10/30 PNE bacitracin ointment 500 units/g, 4 td + oral placebo 6 days erythromycin 250 mg 4 td + placebo cream, 6 days Six days, cured/improved LTFU: 0/60 SE: mild abdominal cramps E 2/15, B 0/15
Participants
Interventions
Outcomes Notes
McLinn 1988 Methods 1986 Feb to May Scottsdale Arizona USA outpatients only impetigo > 6 months, average 5.5 yrs. S.aureus 43/60, S.pyogenes 17/60 PE mupirocin ointment 2%, 3 td, 7 to 9 days erythromycin 30 to 40/mg/kg/day in 3 to 4 doses, 7 to 9 days 8 to 12 days, very much improved/ improved/no change
47
Participants
Interventions
Outcomes
McLinn 1988
(Continued)
Notes
LTFU: 0 SE: M: 0/30, E 6/30 (gastrointestinal)
Risk of bias Item Allocation concealment? Mertz 1989 Methods time NR San Juan Puerto Rico outpatients only impetigo 6 m to 32 yrs, average 5.4 yrs M/F 27/26 S.aureus 44/53, GABHS 37/53 PE mupirocin ointment 2%, 3 td, 7 to 9 days erythromycin 30 to 50 mg/kg/day in 2 doses, 7 to 9 days Seven to nine days, cured/improved LTFU: 0 SE nil reported Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Montero 1996 Methods time NR Multicenter: Columbia Guatemala, Panama, S. Africa. outpatients Range (95/200) 6 m to 12 yrs, M/F 101/94 (all participants) S.aureus 109/200, S.pyogenes 39/200 PNE
Participants
48
Montero 1996
(Continued)
Interventions
azithromycin susp. 10 mg/kg/day once daily, 3 days cefaclor susp. 20 mg/kg/day in 3 doses, 10 days 10 to 14 days, cured + improved LTFU 2/100 in each group SE: A: 3 of 100 C: 2 of 100 (all mild skin side effects)
Outcomes Notes
Risk of bias Item Allocation concealment? Moraes Barbosa 1986 Methods time NR Rio de Janeiro, Brasil Hospital outpatients only impetigo 3 to 14 days, average 11 days. M/F 25/23 S.aureus 100% (inclusion criterion) Four arms: sodium fusidate ointment 2%, 3 td, 10 days chloramfenicol ointment, 3 td, 10 days neomycin/bacitracin ointment, 3 td, 10 days erythromycin oral 50 mg/kg/day, in 4 dd, 10 days Seven days, cure SE: NR study on newborn Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
49
Morley 1988 Methods time NR Plymouth/Bristol/UK general practice Range (89/354) 1 to 92 yrs, average 33 yrs (all participants) M/F 162/192 (all participants) S.aureus 119/344, S.pyogenes 15/344, both 25/344 (all participants) PNE fusidic acid ointment 2%, 3 td, up to 7 days mupirocin ointment 2%, 3 td, up to 7 days Six to eight days, excellent/good SE: no subgroup data
Participants
Interventions
Outcomes Notes Risk of bias Item Allocation concealment? Nolting 1988 Methods
time NR Mnster, Germany outpatients Range (66/80) 1 to 65 yrs, average 24 yrs. M/F 35/31 S.aureus 41/66, GABHS 8/66, both 17/66. PE sulconazole nitrate cream 1%, 2 td, 14 days miconazole nitrate cream 2%, 2 td, 14 days 7 days/14 days, cure SE mild burning S: 0/32 M: 1/34
Participants
Interventions
Outcomes Notes
Risk of bias
50
Nolting 1988
(Continued)
Item Allocation concealment? Park 1993 Methods
1991 Aug to 1992 Sep Pusan / S-Korea outpatients only impetigo Children, 88% 1 to 9 yrs M/F42/35. S. aureus 90% erythromycin 30 to 40 mg/kg/d fusidic acid cream 20 to 40 mg/kg/d, 3 to 5 days cefuroxim 250 mg/day One week, excellent/good LTFU 18 of 77 5 of 77 cases had bullous impetigo SE: NR
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Pruksachat. 1993 Methods 1988 Dec to 1990 Nov Chiang Mai, Thailand outpatients only impetigo 1 m to 8 yrs. median 3.5 yrs, M/F 64/46 (all patients) S. aureus 77/110 PE penicillin V potassium 50 mg/kg/day in 4 doses, 7 days cloxacillin sodium 50 mg/kg/day in 4 doses, 7 days Seven days, cure
51
Participants
Interventions
Outcomes
Pruksachat. 1993
(Continued)
Notes
Bullous and non-bullous impetigo SE: NR
Risk of bias Item Allocation concealment? Rice 1992 Methods 1989 Apr to Nov Baltimore USA outpatients and general practice. Only impetigo 3 m to 16 yrs. MF 53/30 Culture done only in case of therapy failure. PNE erytromycin ethynyl succinate 40 mg/kg/day in 4 doses, 10 days mupirocin ointment 2%, 3 td, 10 days 9 to 11 days,cure/improved/failure LTFU: E 4/46, M 6/47 SE: stomach ache/ diarrhea/ vomiting/itching/ burning (%) E 24/10/7/5/0 M 2/2/0/12/10 Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Rodriguez 1993 Methods time NR. Multicentre: Costa Rica, Guatemala, Panama, Venezuela. outpatients, Range (39/118) 2 to 12 yrs, mean 5 yrs, M/F NR S. aureus 69/118, S. pyogenes 9/118 (all participants) PNE Authors judgement Unclear Description B - Unclear
Participants
52
Rodriguez 1993
(Continued)
Interventions
Three arms: azithromycin 10 mg/kg/day (max. 500), once daily, 3 days dicloxacillin12.5 to 25 mg/kg/day in 4 doses, 7 days, see notes ucloxacillin 500 to 2000 mg/day in 4 doses, see notes Seven to ten days, cure/improved/failure Randomisation between A and either D or F; treatment groups D and F are combined in results SE: A: 2/25, D/F: 2/14 (gastrointestinal)
Outcomes Notes
Risk of bias Item Allocation concealment? Rojas 1985 Methods time NR Dominican Republic hospital outpatients only impetigo age, M/F ratio NR bacterial results NR PE mupirocin ointment 2%, 3 td, 10 to 12 days placebo/vehicle, 3 td, 10 to 12 days 7 to 12 days,cure/improved SE: mupirocin 0/52. vehicle 1/52 (nausea/vomiting) Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes Risk of bias Item Allocation concealment?
Authors judgement No
Description C - Inadequate
53
Ruby 1973 Methods 1972 summer Dallas USA outpatients only impetigo Children, M/F 43/59 only GABHS 33/102, both S. aureus and GABHS 57/102 PNE Five arms: phenoxymethyl penicillin 40 to 60,000 units/kg/day in 3 doses + HS phenoxymethyl penicillin 40 to 60,000 units/kg/day in 3 doses HS+ placebo placebo, 3 td bacitracin ointment, 2 td Five days, cure SE: NR
Participants
Interventions
Sutton 1992 Methods time NR United Kingdom general practice (n = 20) only impetigo (only facial) 1 m to 77 yrs, average 22 yrs. M/F 84/93 S. aureus 68/177 PNE fusidic acid cream 3 td, 6 to 8 days mupirocin ointment 3 td, 6 to 8 days Eight days, cure + improved skin SE: FA 2/104 M 4/97
54
Participants
Interventions
Outcomes Notes
Sutton 1992
(Continued)
Risk of bias Item Allocation concealment? Tack 1997 Methods 1992 July to 1993 Aug multicentre US outpatients. Range (225/394) 0 to 13 yrs (median 5.4) M/F 217/197 S. aureus 284/394 (all participants) PE cefdinir 7 mg/kg/day , 2 td, 10 days cephalexin 10 mg/kg/day, 4 td, 10 days 7 to 14 day, cure SE: no subgroup data available Authors judgement Unclear Description B - Unclear
Participants
Interventions
Tack 1998 Methods 1992 Jan to Dec multicenter USA outpatients Range (62/952) 13 to 88 yrs, M/F 564/388 (all participants), S. aureus 308/382 (all participants) PE cefdinir caps 300 mg, 2 td, 10 days cephalexin caps 500 mg, 4 td, 10 days 7 to 16 days, cure/improved SE: no subgroup data available included only participants that had pathogen susceptible to both study drugs
55
Participants
Interventions
Outcomes Notes
Tack 1998
(Continued)
Risk of bias Item Allocation concealment? Tamayo 1991 Methods time NR Mexico outpatients only impetigo 6 m to 12 yrs, average 4 yrs 8 m. M/F 14/16 S. aureus 18/30, S. pyogenes 4/30, both 1/30 Part. excluded: not clear rifamycin spray, 2 td, 7 days mupirocin ointment 2%, 2td, 7 days One week, cure/improved SE: nil reported Both primary (n = 17) and secondary (n = 13) impetigo participants Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Tassler 1993 Methods time NR. Multicentre (Europe and S. America) hospital admitted and outpatients Range (42/172) Age 18 to 99 yrs, M/F 159/125 (all part) S. aureus 58% (all participants) PE eroxacin 400 mg, 1 td, 7 to 21 days amoxicillin/clavulanic acid tablets 500/125 mg, 3 td, 7 to 21 days Seven days, cure
56
Participants
Interventions
Outcomes
Tassler 1993
(Continued)
Notes Risk of bias Item Allocation concealment?
SE: no subgroup data available
Vainer 1986 Methods 1982 Mar to 1984 Jan Denmark general practice only impetigo Age 1 to 77, average 11 yrs M/F 71/57 No bacterial culture done, PNE fusidic acid cream 2% Tetracycline/polymyxin B ointment neomycin/bacitracin ointment One week, cure/improved LTFU: 6 of 134 SE: total 3% FA; skin rash 1/43. T+P and N+B: burning and itching both one
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Wachs 1976 Methods 1974 multicenter USA outpatients only impetigo (secondary) age/sex NR S. aureus 62/79 PNE Authors judgement Unclear Description B - Unclear
Participants
57
Wachs 1976
(Continued)
Interventions
bethametasone valerate cream, 3 td gentamycin cream, 3 td bethametasone + gentamycin cream, 3 td Three weeks, excellent result SE: NR Secondary impetigo (impetiginised atopic dermatitis)
Outcomes Notes
Risk of bias Item Allocation concealment? Wainscott 1985 Methods time NR London, United Kingdom outpatients and general practice Range (16/39) Age NR M/F 25/14 (all participants) S. aureus 31/48 (all participants) Part. excluded: not clear mupirocin ointment 2%, 2 td, 7 to 14 days chlortetracycline cream 3%, 2 td, 7 to 14 days Seven days, cure/improved SE: nil reported Authors judgement Unclear Description B - Unclear
Participants
Interventions
58
Welsh 1987 Methods time NR Monterrey, Mexico outpatients Range (15/60) Age NR, M/F32/28 S. aureus 47/50 PNE mupirocin ointment 2%, 3 td, 5 to 10 days ampicillin 50 mg, 4 td, 5 to 10 days Ten days, cure/improved LTFU 2/15 SE: nil reported
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? White 1989 Methods 1985 to 1987 United Kingdom general practice Range (155/390) Age 11 m to 84 yrs, M/F NR S. aureus 43% (all participants) PNE mupirocin ointment 2%, 2 td, 7 days fusidic acid ointment 2%, 3 td, 7 days Seven days, cure/improved SE: minor itching or burning M: 6/263 FA: 2/127 (all participants) Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes Notes
Risk of bias Item Authors judgement Description
59
White 1989
(Continued)
Allocation concealment? Wilkinson 1988 Methods
Unclear
B - Unclear
time NR Quebec, Canada outpatients Range (10/50) Age/ sex NR S. aureus 18/50 (all participants) Part. excluded: not clear mupirocin 2%, 3 td, 7 days polymyxin B-neomycin (Neosporin), 3 td, 7 days Seven days, cure/improved SE: rash: M: 0/24 N: 1/26 (all participants)
Participants
Interventions
Outcomes Notes
all participants = data from all participants in the study, not just the impetigo participants; approx = approximately; GABHS=Group A beta Hemolytic Streptococcus; HS=hexachlorophene scrubs; LTFU = lost to follow up; M/F=male/female; NR=not reported; part = participants; PE = participants excluded from study when culture negative; PNE = participants not excluded; range = study on range of skin infections, including impetigo (proportion impetigo patients of all participants); SE=side effects; td = times daily; m = months; yrs = years; dd=daily doses; ds = days
60
Characteristics of excluded studies [ordered by study ID]
Alavena 1987 Anonymous 1998 Arata 1983 Arata 1994 Arosemena 1977 Azimi 1999 Baldwin 1981 Ballantyne 1982 Bastin 1982 Bernard 1997 Bin Jaafar 1987 Burnett 1963 Cassels-Brown 1981 Colin 1988 Cordero 1976 Dillon 1970 Dillon 1979 Drehobl 1997 El Mofty 1990 Esterly 1970 Faingezicht 1992 Fedorovskaya 1989
inadequate randomisation (excluded during quality score phase) results not separately described for impetigo participants; no randomisation inadequate randomisation (serial allocation) results not separately described for impetigo participants results not separately described for impetigo participants; only 6/343 patients had impetigo results not separately described for impetigo participants same drug compared results not separately described for impetigo participants; no randomisation results not separately described for impetigo patients results not separately described for impetigo participants. requested, no reply no impetigo ( pyoderma) no randomisation (excluded in quality score phase) unacceptable design, no rct results not separately described for impetigo participants only one impetigo participant no randomisation (excluded during quality phase) results not separately described for impetigo participants results not separately described for impetigo participants. requested, no reply results not separately described for impetigo participants no randomisation (excluded during quality score phase) results not separately described for impetigo participants inadequate randomisation
61
(Continued)
Fleisher 1983 Forbes 1952 Golcman 1997 Goldfarb 1987 Gooch 1991 Haning 1992 Harding 1970 Heskel 1992 Jacobs 1992 Jennings 1999 Keeny 1979 Kumakiri 1988 Kumar 1988 Lassus 1990 Lentino 1984 Levenstein 1982 Lewis 1985 Linder 1993 Lipets 1987 MacKenna 1945 Macotela-Ruiz 1988 Mallory 1991 McCarty 1992
results not separately described for impetigo participants same drug compared results not separately described for impetigo participants. Requested, no reply results not separately described for impetigo participants results not separately described for impetigo participants results not separately described for impetigo participants one drug (ucloxacillin)in two doses; results for impetigo participants not separately described results not separately described for impetigo participants results not separately described for impetigo participants one impetigo participant results not separately described for impetigo participants one impetigo participant no impetigo; two forms of same drug results not separately described for impetigo participants one impetigo participant results not separately described for impetigo participants results not separately described for impetigo participants results not separately described for impetigo participants no comparison made inadequate randomisation./serial allocation, excluded during quality scoring phase. results not separately described for impetigo participants. requested, no reply. results not separately described for impetigo participants results not separately described for impetigo participants
62
(Continued)
McMillan 1969 Milidi d Silva 1985 Nakayama 1983 Neldner 1991 Nichols 1997 Nicolle 1990 Nolting 1992 Orecchio 1986 Palazzini 1993 Parish 1984 Parish 1991 Parish 1997 Pien 1983 Powers 1991 Powers 1993 Puspenogoro 1990 Risser 1985 Saenz 1985 Salzberg 1972 Schupbach 1992 Schwartz 1996 Smith 1985 Smith 1993
results not separately described for impetigo participants results not separately described for impetigo participants results not separately described for impetigo participants. no rct results not separately described for impetigo participants results not separately described for impetigo participants results not separately described for impetigo participants no impetigo (pyoderma) results not separately described for impetigo participants results not separately described for impetigo participants results not separately described for impetigo participants results not separately described for impetigo participants results not separately described for impetigo participants results not separately described for impetigo participants no separate results for clinical cure only two impetigo participants one impetigo participant results not separately described for impetigo participants results not separately described for impetigo participants one impetigo participant results not separately described for impetigo participants one impetigo participant results not separately described for impetigo participants one impetigo participant
63
(Continued)
Sobye 1966 Stevens 1993 Tack 1991 Urbach 1966 Villiger 1986 Wachs 1992 Wolbling 1987 Wong 1989 Yura 1988
results not separately described for impetigo participants ve participants with pyoderma results not separately described for impetigo participants; same drug compared. no randomisation described. (exclude during quality score phase) results not separately described for impetigo participants results not separately described for impetigo participants two doses of one drug compared results not separately described for impetigo participants results not separately described for impetigo participants
64
DATA AND ANALYSES
Comparison 1. Non-bullous impetigo: topical antibiotic versus placebo
Outcome or subgroup title 1 cure/improvement 1.1 mupirocin 1.2 fusidic acid 1.3 bacitracin
No. of studies 5 3 1 1
No. of participants 365 173 156 36
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
Effect size 6.49 [3.93, 10.73] 5.40 [2.79, 10.45] 8.65 [3.88, 19.29] 3.97 [0.15, 104.18]
Comparison 2. Non-bullous impetigo: topical antibiotic versus another topical antibiotic
Outcome or subgroup title
No. of studies
No. of participants 807 440 17 32 16 14 8 84 87 66 43
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
Effect size 1.56 [1.09, 2.24] 1.22 [0.69, 2.16] 13.91 [0.62, 312.60] 10.33 [0.51, 209.95] 12.0 [0.96, 150.69] 2.6 [0.09, 75.49] 1.36 [0.04, 46.65] 0.79 [0.33, 1.93] 1.16 [0.49, 2.73] 6.11 [0.67, 55.51] 3.31 [0.90, 12.13]
1 cure/improvement 12 1.1 mupirocin versus fusidic 4 acid 1.2 mupirocin versus 1 rifamycin 1.3 mupirocin versus 1 neomycin 1.4 mupirocin versus 1 bacitracin 1.5 mupirocin versus 1 chlortetracycline 1.6 mupirocin versus 1 polymyxin B/neomycin 1.7 fusidic acid versus 1 neomycin/bacitracin 1.8 fusidic acid versus 1 tetracycline/polymyxin B 1.9 sulcanozol versus 1 micanazol 1.10 1 hydrocortisone+hydroxyquinoline versus hydrocortisone+miconazole
65
Comparison 3. Non-bullous impetigo: topical antibiotic versus oral antibiotic
Outcome or subgroup title 1 cure/improvement 1.1 mupirocin versus erythromycin 1.2 mupirocin versus erythromycin: high quality studies 1.3 mupirocin versus dicloxacillin 1.4 mupirocin versus cephalexin 1.5 mupirocin versus ampicillin 1.6 fusidic acid versus erythromycin 1.7 fusidic acid versus cefuroxim 1.8 bacitracin versus erythromycin 1.9 bacitracin versus penicillin 1.10 bacitracin versus cephalexin
No. of studies 16 10 3
No. of participants 1021 581 197
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
Effect size 1.60 [1.12, 2.29] 1.76 [1.05, 2.97] 3.73 [1.35, 10.34]
1 1 1 1 1 1 1 1
53 17 13 37 40 30 34 19
Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
3.00 [0.12, 77.03] 0.67 [0.03, 12.84] 8.0 [0.46, 139.29] 8.38 [1.77, 39.69] 1.31 [0.37, 4.64] 0.25 [0.05, 1.14] 0.33 [0.03, 3.58] 0.06 [0.00, 0.67]
Comparison 4. Non-bullous impetigo: topical antibiotics versus disinfecting treatments
Outcome or subgroup title 1 cure/improvement 1.1 bacitracin versus hexachlorophene 1.2 fusidic acid versus hydrogen peroxide
No. of studies 2 1 1
No. of participants 292 36 256
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
Effect size 1.84 [1.03, 3.29] 3.97 [0.15, 104.18] 1.79 [0.99, 3.23]
66
Comparison 5. Non-bullous impetigo: oral antibiotics versus placebo
Outcome or subgroup title 1 cure/improvement 1.1 penicillin
No. of studies 1 1
No. of participants 38 38
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
Effect size 9.26 [0.44, 192.72] 9.26 [0.44, 192.72]
Comparison 6. Non-bullous impetigo: oral antibiotic (cephalosporin) versus another oral antibiotic
Outcome or subgroup title 1 cure/improvement 1.1 cephalexin versus penicillin 1.2 cephalexin versus erythromycin 1.3 cephalexin versus azithromycin 1.4 cefaclor versus azithromycin 1.5 cefaclor versus amoxicillin/ clavulanic acid 1.6 cefadroxil versus penicillin 1.7 cefadroxil versus ucloxacillin 1.8 cefuroxim versus erythromycin
No. of studies 7 1 1 1 1 1 1 1 1
No. of participants 394 48 48 18 95 34 50 60 41
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
Effect size 1.67 [0.93, 3.00] 15.67 [0.83, 295.88] 2.88 [0.11, 74.23] 3.0 [0.40, 22.71] 1.79 [0.29, 11.25] 0.54 [0.08, 3.74] 0.91 [0.17, 5.03] 0.25 [0.05, 1.30] 6.40 [1.44, 28.44]
Comparison 7. Non-bullous impetigo: oral cephalosporin versus other oral cephalosporin
Outcome or subgroup title 1 cure/improvement 1.1 cephalexin versus cefadroxil 1.2 cephalexin versus cefdinir 1.3 cefaclor versus cefdinir
No. of participants 294 96 185 13
Effect size 0.56 [0.24, 1.31] 0.87 [0.21, 3.71] 0.48 [0.14, 1.57] 0.29 [0.02, 3.52]
67
Comparison 8. Non-bullous impetigo: oral macrolide versus penicillin
Outcome or subgroup title 1 cure/improvement 1.1 erythromycin versus penicillin V 1.2 erythromycin versus dicloxacillin 1.3 azithromycin versus cloxacillin 1.4 azithromycin versus ucloxacillin/dicloxacillin 1.5 clindamycin versus dicloxacillin
No. of studies 6 2 1 1 1 1
No. of participants 234 79 58 16 39 42
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
Effect size 1.99 [0.92, 4.34] 8.82 [1.49, 52.01] 2.90 [0.11, 74.13] 2.33 [0.29, 18.96] 0.43 [0.08, 2.42] 1.10 [0.16, 7.39]
Comparison 9. Non-bullous impetigo: oral macrolide versus another oral macrolide
Outcome or subgroup title 1 cure/improvement 1.1 azithromycin versus erythromycin
No. of studies 1 1
Effect size 1.90 [0.62, 5.83] 1.90 [0.62, 5.83]
Comparison 10. Non-bullous impetigo: oral penicillin versus other oral antibiotic (including penicillin)
Outcome or subgroup title 1 cure/improvement 1.1 amoxicillin+clavulanic acid versus amoxicillin 1.2 amoxicillin+clavulanic acid versus eroxacin 1.3 cloxacillin versus penicillin
No. of participants
Effect size Subtotals only 9.8 [1.09, 88.23] 1.68 [0.37, 7.63] 13.74 [4.36, 43.24]
44 42 166
68
Comparison 11. Non-bullous impetigo: other comparisons of oral antibiotics
Outcome or subgroup title 1 cure/improvement 1.1 lomeoxacin versus noroxacin
No. of studies 1 1
Effect size 2.5 [0.37, 16.89] 2.5 [0.37, 16.89]
Comparison 12. Non-bullous impetigo: oral antibiotics versus disinfecting treatments
Outcome or subgroup title 1 cure/improvement 1.1 penicillin versus hexachlorophene
No. of studies 1 1
Effect size 9.26 [0.44, 192.72] 9.26 [0.44, 192.72]
Comparison 13. Non-bullous impetigo: disinfecting treatments versus placebo
Outcome or subgroup title 1 cure/improvement 1.1 topical hexachlorophene
No. of studies 1 1
Effect size Not estimable Not estimable
Comparison 14. Bullous impetigo: topical antibiotic versus another topical antibiotic
Outcome or subgroup title 1 cure/improvement 1.1 fusidic acid versus neomycin/bacitracin 1.2 fusidic acid versus chloramphenicol 1.3 chloramphenicol versus neomycin/bacitracin
No. of participants
Effect size Subtotals only 55.0 [4.30, 703.43] 25.00 [2.92, 213.99] 2.2 [0.17, 28.14]
24 24 24
69
Comparison 15. Bullous impetigo: topical antibiotic versus oral antibiotic
Outcome or subgroup title 1 cure/improvement 1.1 fusidic acid versus erythromycin 1.2 neomycin/bacitracin versus erythromycin 1.3 chloramphenicol versus erythromycin 1.4 any topical antibiotic versus any oral antibiotic
No. of studies 1 1 1 1 1
No. of participants 120 24 24 24 48
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
Effect size 0.40 [0.18, 0.88] 3.57 [0.53, 23.95] 0.06 [0.01, 0.68] 0.14 [0.02, 0.96] 0.40 [0.11, 1.53]
Comparison 16. Bullous impetigo; oral antibiotic versus another oral antibiotic
Outcome or subgroup title 1 cure/improvement 1.1 cephalexin versus dicloxacillin
No. of studies 1 1
Effect size 3.39 [0.62, 18.49] 3.39 [0.62, 18.49]
Comparison 17. Secondary impetigo: steroid versus antibiotic
Outcome or subgroup title 1 cure/improvement 1.1 betamethasone versus gentamycin
No. of studies 1 1
Effect size 2.97 [0.97, 9.12] 2.97 [0.97, 9.12]
Comparison 18. Secondary impetigo: steroid+antibiotic versus steroid
Outcome or subgroup title 1 cure/improvement 1.1 betamethasone+gentamycin versus betamethasone
No. of studies 1 1
Effect size 2.06 [0.65, 6.54] 2.06 [0.65, 6.54]
70
Comparison 19. Secondary impetigo: steroid+antibiotic versus antibiotic
Outcome or subgroup title 1 cure/improvement 1.1 betamethasone+gentamycin versus gentamycin
No. of studies 1 1
Effect size 6.11 [1.84, 20.31] 6.11 [1.84, 20.31]
Comparison 20. Secondary impetigo: oral antibiotic versus another oral antibiotic
Outcome or subgroup title 1 cure/improvement 1.1 cephalexin versus enoxacin
No. of studies 1 1
Effect size 0.5 [0.04, 6.68] 0.5 [0.04, 6.68]
Analysis 1.1. Comparison 1 Non-bullous impetigo: topical antibiotic versus placebo, Outcome 1 cure/improvement.
Review: Interventions for impetigo
Comparison: 1 Non-bullous impetigo: topical antibiotic versus placebo Outcome: 1 cure/improvement
Study or subgroup
topical antibiotic n/N
placebo n/N
Odds Ratio M-H,Fixed,95% CI
Weight
1 mupirocin Eells 1986 Gould 1984 Rojas 1985 14/17 10/14 34/50 8/19 7/21 15/52 10.7 % 12.9 % 37.9 % 6.42 [ 1.37, 30.05 ] 5.00 [ 1.15, 21.80 ] 5.24 [ 2.25, 12.20 ]
Subtotal (95% CI)
81
92
61.6 %
5.40 [ 2.79, 10.45 ]
Total events: 58 (topical antibiotic), 30 (placebo) Heterogeneity: Chi2 = 0.06, df = 2 (P = 0.97); I2 =0.0% Test for overall effect: Z = 5.00 (P < 0.00001) 2 fusidic acid Koning 2002 42/76 10/80
0.01 0.1 1 10 100
35.1 %
8.65 [ 3.88, 19.29 ]
favours placebo
favours topical ab
(Continued . . . )
(. . .
Study or subgroup topical antibiotic n/N placebo n/N Odds Ratio M-H,Fixed,95% CI Weight
Continued) Odds Ratio
M-H,Fixed,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 5.27 (P < 0.00001) 3 bacitracin Ruby 1973
76
80
35.1 %
8.65 [ 3.88, 19.29 ]
Total events: 42 (topical antibiotic), 10 (placebo)
1/16
0/20
3.3 %
3.97 [ 0.15, 104.18 ]
Subtotal (95% CI)

Total events: 1 (topical antibiotic), 0 (placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.83 (P = 0.41)
16
20
3.3 %
3.97 [ 0.15, 104.18 ]
Total (95% CI)
173
192
100.0 %
6.49 [ 3.93, 10.73 ]
Total events: 101 (topical antibiotic), 40 (placebo) Heterogeneity: Chi2 = 0.95, df = 4 (P = 0.92); I2 =0.0% Test for overall effect: Z = 7.30 (P < 0.00001)
0.01
0.1
10
100
favours placebo
favours topical ab
Analysis 2.1. Comparison 2 Non-bullous impetigo: topical antibiotic versus another topical antibiotic, Outcome 1 cure/improvement.
Comparison: 2 Non-bullous impetigo: topical antibiotic versus another topical antibiotic Outcome: 1 cure/improvement
Study or subgroup
antibiotic A n/N
antibiotic B n/N
Weight
1 mupirocin versus fusidic acid Gilbert 1989 Morley 1988 Sutton 1992 White 1989 4/8 32/38 82/84 81/106 6/11 45/51 90/93 33/49 5.3 % 12.8 % 4.3 % 22.4 % 0.83 [ 0.13, 5.17 ] 0.71 [ 0.21, 2.41 ] 1.37 [ 0.22, 8.38 ] 1.57 [ 0.74, 3.31 ]
Subtotal (95% CI)
236
204
44.9 %
1.22 [ 0.69, 2.16 ]
Total events: 199 (antibiotic A), 174 (antibiotic B) Heterogeneity: Chi2 = 1.38, df = 3 (P = 0.71); I2 =0.0% Test for overall effect: Z = 0.68 (P = 0.50)
0.005
0.1
10
200
favours antibiotic B
favours antibiotic A
(Continued . . . )
72
(. . .
Study or subgroup antibiotic A n/N 2 mupirocin versus rifamycin Tamayo 1991 8/8 5/9 0.6 % antibiotic B n/N Odds Ratio M-H,Fixed,95% CI Weight
M-H,Fixed,95% CI
13.91 [ 0.62, 312.60 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.66 (P = 0.097) 3 mupirocin versus neomycin Kennedy 1985
0.6 %
13.91 [ 0.62, 312.60 ]
Total events: 8 (antibiotic A), 5 (antibiotic B)
15/15
13/17
0.8 %
10.33 [ 0.51, 209.95 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.52 (P = 0.13) 4 mupirocin versus bacitracin Bass 1997
15
17
0.8 %
10.33 [ 0.51, 209.95 ]
6/7
3/9
0.8 %
12.00 [ 0.96, 150.69 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.92 (P = 0.054) 5 mupirocin versus chlortetracycline Wainscott 1985
0.8 %
12.00 [ 0.96, 150.69 ]
6/6
7/8
1.0 %
2.60 [ 0.09, 75.49 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.56 (P = 0.58) 6 mupirocin versus polymyxin B/neomycin Wilkinson 1988
1.0 %
2.60 [ 0.09, 75.49 ]
2/2
5/6
1.2 %
1.36 [ 0.04, 46.65 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.17 (P = 0.86) 7 fusidic acid versus neomycin/bacitracin Vainer 1986
1.2 %
1.36 [ 0.04, 46.65 ]
26/43
27/41
23.0 %
0.79 [ 0.33, 1.93 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.51 (P = 0.61)
43
41
23.0 %
0.79 [ 0.33, 1.93 ]
8 fusidic acid versus tetracycline/polymyxin B Vainer 1986 26/43 25/44 20.6 % 1.16 [ 0.49, 2.73 ]
Subtotal (95% CI)

43
44
20.6 %
1.16 [ 0.49, 2.73 ]
0.005
0.1
10
200
(Continued . . . )
(. . .
Study or subgroup antibiotic A n/N 9 sulcanozol versus micanazol Nolting 1988 5/32 1/34 1.7 % antibiotic B n/N Odds Ratio M-H,Fixed,95% CI Weight
M-H,Fixed,95% CI
6.11 [ 0.67, 55.51 ]
Subtotal (95% CI)

32
34
1.7 %
6.11 [ 0.67, 55.51 ]
10 hydrocortisone+hydroxyquinoline versus hydrocortisone+miconazole Jaffe 1986 13/24 5/19 5.4 % 3.31 [ 0.90, 12.13 ]
Subtotal (95% CI)

Heterogeneity: not applicable
24
19
5.4 %
3.31 [ 0.90, 12.13 ]
Total events: 13 (antibiotic A), 5 (antibiotic B) Test for overall effect: Z = 1.81 (P = 0.071)
Total (95% CI)
416
391
100.0 %
1.56 [ 1.09, 2.24 ]
Total events: 306 (antibiotic A), 265 (antibiotic B) Heterogeneity: Chi2 = 13.51, df = 12 (P = 0.33); I2 =11% Test for overall effect: Z = 2.42 (P = 0.016)
0.005
0.1
10
200
74
Analysis 3.1. Comparison 3 Non-bullous impetigo: topical antibiotic versus oral antibiotic, Outcome 1 cure/improvement.
Comparison: 3 Non-bullous impetigo: topical antibiotic versus oral antibiotic Outcome: 1 cure/improvement
Study or subgroup
oral antibiotic n/N
Weight
1 mupirocin versus erythromycin Barton 1989 Britton 1990 Dagan 1992 Dux 1986 Esterly 1991 Goldfarb 1988 Gratton 1987 McLinn 1988 Mertz 1989 Rice 1992 47/49 20/22 45/46 17/24 21/22 29/29 7/7 28/30 26/28 30/41 43/48 24/26 33/43 8/12 18/20 27/29 6/8 25/30 24/25 34/42 3.7 % 4.1 % 1.5 % 6.4 % 1.8 % 0.9 % 0.8 % 3.4 % 3.7 % 18.6 % 2.73 [ 0.50, 14.83 ] 0.83 [ 0.11, 6.46 ] 13.64 [ 1.66, 111.82 ] 1.21 [ 0.27, 5.38 ] 2.33 [ 0.20, 27.91 ] 5.36 [ 0.25, 116.76 ] 5.77 [ 0.23, 143.37 ] 2.80 [ 0.50, 15.73 ] 0.54 [ 0.05, 6.36 ] 0.64 [ 0.23, 1.81 ]
Subtotal (95% CI)
298
283
45.1 %
1.76 [ 1.05, 2.97 ]
Total events: 270 (topical antibiotic), 242 (oral antibiotic) Heterogeneity: Chi2 = 10.54, df = 9 (P = 0.31); I2 =15% Test for overall effect: Z = 2.14 (P = 0.033) 2 mupirocin versus erythromycin: high quality studies Britton 1990 Dagan 1992 McLinn 1988 20/22 45/46 28/30 24/26 33/43 25/30 4.1 % 1.5 % 3.4 % 0.83 [ 0.11, 6.46 ] 13.64 [ 1.66, 111.82 ] 2.80 [ 0.50, 15.73 ]
Subtotal (95% CI)
98
99
9.1 %
3.73 [ 1.35, 10.34 ]
Total events: 93 (topical antibiotic), 82 (oral antibiotic) Heterogeneity: Chi2 = 3.62, df = 2 (P = 0.16); I2 =45% Test for overall effect: Z = 2.53 (P = 0.011) 3 mupirocin versus dicloxacillin Arredondo 1987 26/26 26/27 1.0 % 3.00 [ 0.12, 77.03 ]
Subtotal (95% CI)

26
27
1.0 %
3.00 [ 0.12, 77.03 ]
Total events: 26 (topical antibiotic), 26 (oral antibiotic)
0.005
0.1
10
200
favours oral antibio
favours topical anti
(Continued . . . )
75
(. . .
Study or subgroup topical antibiotic n/N 4 mupirocin versus cephalexin Bass 1997 6/7 9/10 2.2 % oral antibiotic n/N Odds Ratio M-H,Fixed,95% CI Weight
M-H,Fixed,95% CI
0.67 [ 0.03, 12.84 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.27 (P = 0.79) 5 mupirocin versus ampicillin Welsh 1987
10
2.2 %
0.67 [ 0.03, 12.84 ]
8/9
2/4
0.6 %
8.00 [ 0.46, 139.29 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.43 (P = 0.15) 6 fusidic acid versus erythromycin Park 1993
0.6 %
8.00 [ 0.46, 139.29 ]
11/18
3/19
2.3 %
8.38 [ 1.77, 39.69 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 2.68 (P = 0.0074) 7 fusidic acid versus cefuroxim Park 1993
18
19
2.3 %
8.38 [ 1.77, 39.69 ]
11/18
12/22
8.7 %
1.31 [ 0.37, 4.64 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.42 (P = 0.68) 8 bacitracin versus erythromycin Koranyi 1976
18
22
8.7 %
1.31 [ 0.37, 4.64 ]
5/15
10/15
13.8 %
0.25 [ 0.05, 1.14 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.79 (P = 0.074) 9 bacitracin versus penicillin Ruby 1973
15
15
13.8 %
0.25 [ 0.05, 1.14 ]
1/16
3/18
5.5 %
0.33 [ 0.03, 3.58 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.91 (P = 0.36) 10 bacitracin versus cephalexin Bass 1997
16
18
5.5 %
0.33 [ 0.03, 3.58 ]
3/9
9/10
11.7 %
0.06 [ 0.00, 0.67 ]
Subtotal (95% CI)

10
11.7 %
0.06 [ 0.00, 0.67 ]
0.005
0.1
10
200
(Continued . . . )
(. . .
Study or subgroup topical antibiotic n/N Test for overall effect: Z = 2.28 (P = 0.023) oral antibiotic n/N Odds Ratio M-H,Fixed,95% CI Weight
M-H,Fixed,95% CI
Total (95% CI)
514
507
100.0 %
1.60 [ 1.12, 2.29 ]
Total events: 434 (topical antibiotic), 398 (oral antibiotic) Heterogeneity: Chi2 = 35.68, df = 20 (P = 0.02); I2 =44% Test for overall effect: Z = 2.57 (P = 0.010)
0.005
0.1
10
200
Analysis 4.1. Comparison 4 Non-bullous impetigo: topical antibiotics versus disinfecting treatments, Outcome 1 cure/improvement.
Comparison: 4 Non-bullous impetigo: topical antibiotics versus disinfecting treatments Outcome: 1 cure/improvement
Study or subgroup
disinfectant n/N
Weight
1 bacitracin versus hexachlorophene Ruby 1973 1/16 0/20 2.4 % 3.97 [ 0.15, 104.18 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.83 (P = 0.41) 2 fusidic acid versus hydrogen peroxide Christensen 1994
16
20
2.4 %
3.97 [ 0.15, 104.18 ]
Total events: 1 (topical antibiotic), 0 (disinfectant)
105/128
92/128
97.6 %
1.79 [ 0.99, 3.23 ]
Subtotal (95% CI)

128
128
97.6 %
1.79 [ 0.99, 3.23 ]
Total events: 105 (topical antibiotic), 92 (disinfectant)
Total (95% CI)
144
148
100.0 %
1.84 [ 1.03, 3.29 ]
Total events: 106 (topical antibiotic), 92 (disinfectant) Heterogeneity: Chi2 = 0.22, df = 1 (P = 0.64); I2 =0.0% Test for overall effect: Z = 2.05 (P = 0.040)
0.01
0.1
10
100
favours disinfectant
77
Analysis 5.1. Comparison 5 Non-bullous impetigo: oral antibiotics versus placebo, Outcome 1 cure/improvement.
Comparison: 5 Non-bullous impetigo: oral antibiotics versus placebo Outcome: 1 cure/improvement
Study or subgroup
oral antibiotic n/N
placebo n/N
Weight
1 penicillin Ruby 1973 3/18 0/20 100.0 % 9.26 [ 0.44, 192.72 ]
Total (95% CI)

18
20
100.0 %
9.26 [ 0.44, 192.72 ]
Total events: 3 (oral antibiotic), 0 (placebo) Test for overall effect: Z = 1.44 (P = 0.15)
0.005
0.1
10
200
favours placebo
Analysis 6.1. Comparison 6 Non-bullous impetigo: oral antibiotic (cephalosporin) versus another oral antibiotic, Outcome 1 cure/improvement.
Comparison: 6 Non-bullous impetigo: oral antibiotic (cephalosporin) versus another oral antibiotic Outcome: 1 cure/improvement
Study or subgroup
cephalosporin n/N
other oral antibioti n/N
Weight
1 cephalexin versus penicillin Demidovich 1990 23/23 19/25 2.2 % 15.67 [ 0.83, 295.88 ]
Subtotal (95% CI)

23
25
2.2 %
15.67 [ 0.83, 295.88 ]
Total events: 23 (cephalosporin), 19 (other oral antibioti) Test for overall effect: Z = 1.84 (P = 0.066) 2 cephalexin versus erythromycin Demidovich 1990 23/23 24/25 2.8 % 2.88 [ 0.11, 74.23 ]
Subtotal (95% CI)

23
25
2.8 %
2.88 [ 0.11, 74.23 ]
Total events: 23 (cephalosporin), 24 (other oral antibioti)
0.005
0.1
10
200
Favours other oral a
favours cephalospori
(Continued . . . )
78
(. . .
Study or subgroup cephalosporin n/N Test for overall effect: Z = 0.64 (P = 0.52) 3 cephalexin versus azithromycin Kiani 1991 6/8 5/10 6.4 % other oral antibioti n/N Odds Ratio M-H,Fixed,95% CI Weight
Continued)
3.00 [ 0.40, 22.71 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.06 (P = 0.29) 4 cefaclor versus azithromycin Montero 1996
10
6.4 %
3.00 [ 0.40, 22.71 ]
49/51
41/44
9.9 %
1.79 [ 0.29, 11.25 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.62 (P = 0.53) 5 cefaclor versus amoxicillin/clavulanic acid Jaffe 1985
51
44
9.9 %
1.79 [ 0.29, 11.25 ]
13/16
16/18
16.2 %
0.54 [ 0.08, 3.74 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.62 (P = 0.53) 6 cefadroxil versus penicillin Ginsburg 1978
16
18
16.2 %
0.54 [ 0.08, 3.74 ]
21/24
23/26
15.8 %
0.91 [ 0.17, 5.03 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.10 (P = 0.92) 7 cefadroxil versus ucloxacillin Beitner 1996
24
26
15.8 %
0.91 [ 0.17, 5.03 ]
25/33
25/27
38.2 %
0.25 [ 0.05, 1.30 ]
Subtotal (95% CI)

33
27
38.2 %
0.25 [ 0.05, 1.30 ]
Total events: 25 (cephalosporin), 25 (other oral antibioti) Test for overall effect: Z = 1.65 (P = 0.099) 8 cefuroxim versus erythromycin Park 1993 12/22 3/19 8.4 % 6.40 [ 1.44, 28.44 ]
Subtotal (95% CI)

22
19
8.4 %
6.40 [ 1.44, 28.44 ]
Total events: 12 (cephalosporin), 3 (other oral antibioti) Test for overall effect: Z = 2.44 (P = 0.015)
Total (95% CI)
200
194
100.0 %
1.67 [ 0.93, 3.00 ]
Total events: 172 (cephalosporin), 156 (other oral antibioti) Heterogeneity: Chi2 = 12.68, df = 7 (P = 0.08); I2 =45% Test for overall effect: Z = 1.70 (P = 0.089)
0.005
0.1
10
200
Favours other oral a
favours cephalospori
79
Analysis 7.1. Comparison 7 Non-bullous impetigo: oral cephalosporin versus other oral cephalosporin, Outcome 1 cure/improvement.
Comparison: 7 Non-bullous impetigo: oral cephalosporin versus other oral cephalosporin Outcome: 1 cure/improvement
Study or subgroup
cephalosporin A n/N
cephalosporin B n/N
Weight
1 cephalexin versus cefadroxil Hains 1989 41/45 47/51 27.8 % 0.87 [ 0.21, 3.71 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.18 (P = 0.85) 2 cephalexin versus cefdinir Tack 1997 Tack 1998
45
51
27.8 %
0.87 [ 0.21, 3.71 ]
Total events: 41 (cephalosporin A), 47 (cephalosporin B)
73/76 11/17
72/74 15/18
20.4 % 36.5 %
0.68 [ 0.11, 4.17 ] 0.37 [ 0.07, 1.80 ]
Subtotal (95% CI)
93
92
56.9 %
0.48 [ 0.14, 1.57 ]
Total events: 84 (cephalosporin A), 87 (cephalosporin B) Heterogeneity: Chi2 = 0.25, df = 1 (P = 0.62); I2 =0.0% Test for overall effect: Z = 1.21 (P = 0.22) 3 cefaclor versus cefdinir Arata 1989a 2/4 7/9 15.3 % 0.29 [ 0.02, 3.52 ]
Subtotal (95% CI)

15.3 %
0.29 [ 0.02, 3.52 ]
Total events: 2 (cephalosporin A), 7 (cephalosporin B)
Total (95% CI)
142
152
100.0 %
0.56 [ 0.24, 1.31 ]
Total events: 127 (cephalosporin A), 141 (cephalosporin B) Heterogeneity: Chi2 = 0.95, df = 3 (P = 0.81); I2 =0.0% Test for overall effect: Z = 1.33 (P = 0.18)
0.02
0.1
10
50
favours cephalosp B
favours cephalosp A
80
Analysis 8.1. Comparison 8 Non-bullous impetigo: oral macrolide versus penicillin, Outcome 1 cure/improvement.
Comparison: 8 Non-bullous impetigo: oral macrolide versus penicillin Outcome: 1 cure/improvement
Study or subgroup
oral macrolide n/N
penicillin n/N
Weight
1 erythromycin versus penicillin V Barton 1987 Demidovich 1990 14/14 24/25 11/15 19/25 4.1 % 8.4 % 11.35 [ 0.55, 233.12 ] 7.58 [ 0.84, 68.46 ]
Subtotal (95% CI)
39
40
12.5 %
8.82 [ 1.49, 52.01 ]
Total events: 38 (oral macrolide), 30 (penicillin) Heterogeneity: Chi2 = 0.04, df = 1 (P = 0.83); I2 =0.0% Test for overall effect: Z = 2.40 (P = 0.016) 2 erythromycin versus dicloxacillin Barton 1988 28/28 29/30 5.4 % 2.90 [ 0.11, 74.13 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.64 (P = 0.52) 3 azithromycin versus cloxacillin Daniel 1991b
28
30
5.4 %
2.90 [ 0.11, 74.13 ]
Total events: 28 (oral macrolide), 29 (penicillin)
7/10
3/6
12.4 %
2.33 [ 0.29, 18.96 ]
Subtotal (95% CI)

Total events: 7 (oral macrolide), 3 (penicillin) Heterogeneity: not applicable Test for overall effect: Z = 0.79 (P = 0.43)
10
12.4 %
2.33 [ 0.29, 18.96 ]
4 azithromycin versus ucloxacillin/dicloxacillin Rodriguez 1993 18/25 12/14 47.6 % 0.43 [ 0.08, 2.42 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.96 (P = 0.34) 5 clindamycin versus dicloxacillin Blaszcyk 1998
25
14
47.6 %
0.43 [ 0.08, 2.42 ]
23/26
14/16
22.1 %
1.10 [ 0.16, 7.39 ]
Subtotal (95% CI)

26
16
22.1 %
1.10 [ 0.16, 7.39 ]
Total (95% CI)
128
106
100.0 %
1.99 [ 0.92, 4.34 ]
Total events: 114 (oral macrolide), 88 (penicillin) Heterogeneity: Chi2 = 6.16, df = 5 (P = 0.29); I2 =19% Test for overall effect: Z = 1.74 (P = 0.082)
0.005
0.1
10
200
favours penicillin
favours macrolide
81
Analysis 9.1. Comparison 9 Non-bullous impetigo: oral macrolide versus another oral macrolide, Outcome 1 cure/improvement.
Comparison: 9 Non-bullous impetigo: oral macrolide versus another oral macrolide Outcome: 1 cure/improvement
Study or subgroup
oral macrolide A n/N
oral macrolide B n/N
Weight
1 azithromycin versus erythromycin Daniel 1991a 28/35 21/31 100.0 % 1.90 [ 0.62, 5.83 ]
Total (95% CI)

35
31
100.0 %
1.90 [ 0.62, 5.83 ]
Total events: 28 (oral macrolide A), 21 (oral macrolide B)
0.2
0.5
favours macrolide B
favours macrolide A
82
Analysis 10.1. Comparison 10 Non-bullous impetigo: oral penicillin versus other oral antibiotic (including penicillin), Outcome 1 cure/improvement.
Comparison: 10 Non-bullous impetigo: oral penicillin versus other oral antibiotic (including penicillin) Outcome: 1 cure/improvement
Study or subgroup
penicillin A n/N
antibiotic B n/N
Weight
1 amoxicillin+clavulanic acid versus amoxicillin Dagan 1989 21/22 15/22 100.0 % 9.80 [ 1.09, 88.23 ]
Subtotal (95% CI)

22
22
100.0 %
9.80 [ 1.09, 88.23 ]
Total events: 21 (penicillin A), 15 (antibiotic B) Test for overall effect: Z = 2.04 (P = 0.042) 2 amoxicillin+clavulanic acid versus eroxacin Tassler 1993 12/15 19/27 100.0 % 1.68 [ 0.37, 7.63 ]
Subtotal (95% CI)

15
27
100.0 %
1.68 [ 0.37, 7.63 ]
Total events: 12 (penicillin A), 19 (antibiotic B) Test for overall effect: Z = 0.68 (P = 0.50) 3 cloxacillin versus penicillin Gonzalez 1989 Pruksachat. 1993 33/33 42/45 23/43 30/45 13.1 % 86.9 % 58.45 [ 3.37, 1015.02 ] 7.00 [ 1.86, 26.34 ]
Subtotal (95% CI)
78
88
100.0 %
13.74 [ 4.36, 43.24 ]
Total events: 75 (penicillin A), 53 (antibiotic B) Heterogeneity: Chi2 = 1.98, df = 1 (P = 0.16); I2 =50% Test for overall effect: Z = 4.48 (P < 0.00001)
0.001 0.01 0.1 favours antibiotic B
10 100 1000 favours penicillin A
83
Analysis 11.1. Comparison 11 Non-bullous impetigo: other comparisons of oral antibiotics, Outcome 1 cure/improvement.
Comparison: 11 Non-bullous impetigo: other comparisons of oral antibiotics Outcome: 1 cure/improvement
Study or subgroup
lomeoxacin n/N
noroxacin n/N
Weight
1 lomeoxacin versus noroxacin Arata 1989b 6/10 3/8 100.0 % 2.50 [ 0.37, 16.89 ]
Total (95% CI)

10
100.0 %
2.50 [ 0.37, 16.89 ]
Total events: 6 (lomeoxacin), 3 (noroxacin) Test for overall effect: Z = 0.94 (P = 0.35)
0.05
0.2
20
favours noroxacin
favours lomeoxacin
Analysis 12.1. Comparison 12 Non-bullous impetigo: oral antibiotics versus disinfecting treatments, Outcome 1 cure/improvement.
Comparison: 12 Non-bullous impetigo: oral antibiotics versus disinfecting treatments Outcome: 1 cure/improvement
Study or subgroup
oral antibiotic n/N
disinfectant n/N
Weight
1 penicillin versus hexachlorophene Ruby 1973 3/18 0/20 100.0 % 9.26 [ 0.44, 192.72 ]
Total (95% CI)

18
20
100.0 %
9.26 [ 0.44, 192.72 ]
Total events: 3 (oral antibiotic), 0 (disinfectant) Test for overall effect: Z = 1.44 (P = 0.15)
0.005
0.1
10
200
84
Analysis 13.1. Comparison 13 Non-bullous impetigo: disinfecting treatments versus placebo, Outcome 1 cure/improvement.
Comparison: 13 Non-bullous impetigo: disinfecting treatments versus placebo Outcome: 1 cure/improvement
Study or subgroup
disinfectant n/N
placebo n/N
1 topical hexachlorophene Ruby 1973 0/20 0/20 0.0 [ 0.0, 0.0 ]
Total (95% CI)

Total events: 0 (disinfectant), 0 (placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P < 0.00001)
20
20
0.0 [ 0.0, 0.0 ]
0.1 0.2
0.5
10
favours placebo
Analysis 14.1. Comparison 14 Bullous impetigo: topical antibiotic versus another topical antibiotic, Outcome 1 cure/improvement.
Comparison: 14 Bullous impetigo: topical antibiotic versus another topical antibiotic Outcome: 1 cure/improvement
Study or subgroup
topical antibiotic A n/N
topical antibiotic B n/N
Weight
1 fusidic acid versus neomycin/bacitracin Moraes Barbosa 1986 10/12 1/12 100.0 % 55.00 [ 4.30, 703.43 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 3.08 (P = 0.0021) 2 fusidic acid versus chloramphenicol Moraes Barbosa 1986
12
12
100.0 %
55.00 [ 4.30, 703.43 ]
Total events: 10 (topical antibiotic A), 1 (topical antibiotic B)
10/12
2/12
100.0 %
25.00 [ 2.92, 213.99 ]
Subtotal (95% CI)

12
12
100.0 %
25.00 [ 2.92, 213.99 ]
10 100 1000 favours antibiotic A
(Continued . . . )
85
(. . .
Study or subgroup topical antibiotic A n/N Test for overall effect: Z = 2.94 (P = 0.0033) 3 chloramphenicol versus neomycin/bacitracin Moraes Barbosa 1986 2/12 1/12 100.0 % topical antibiotic B n/N Odds Ratio M-H,Fixed,95% CI Weight
M-H,Fixed,95% CI
2.20 [ 0.17, 28.14 ]
Subtotal (95% CI)

12
12
100.0 %
2.20 [ 0.17, 28.14 ]
10 100 1000 favours antibiotic A
Analysis 15.1. Comparison 15 Bullous impetigo: topical antibiotic versus oral antibiotic, Outcome 1 cure/improvement.
Comparison: 15 Bullous impetigo: topical antibiotic versus oral antibiotic Outcome: 1 cure/improvement
Study or subgroup
oral antibiotic n/N
Weight
1 fusidic acid versus erythromycin Moraes Barbosa 1986 10/12 7/12 5.8 % 3.57 [ 0.53, 23.95 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.31 (P = 0.19) 2 neomycin/bacitracin versus erythromycin Moraes Barbosa 1986
12
12
5.8 %
3.57 [ 0.53, 23.95 ]
1/12
7/12
31.9 %
0.06 [ 0.01, 0.68 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 2.28 (P = 0.022) 3 chloramphenicol versus erythromycin Moraes Barbosa 1986
12
12
31.9 %
0.06 [ 0.01, 0.68 ]
2/12
7/12
29.0 %
0.14 [ 0.02, 0.96 ]
Subtotal (95% CI)

12
12
29.0 %
0.14 [ 0.02, 0.96 ]
0.01
0.1
10
100
(Continued . . . )
86
(. . .
Study or subgroup topical antibiotic n/N Test for overall effect: Z = 2.00 (P = 0.045) 4 any topical antibiotic versus any oral antibiotic Moraes Barbosa 1986 13/36 7/12 33.3 % oral antibiotic n/N Odds Ratio M-H,Fixed,95% CI Weight
M-H,Fixed,95% CI
0.40 [ 0.11, 1.53 ]
Subtotal (95% CI)

36
12
33.3 %
0.40 [ 0.11, 1.53 ]
Total (95% CI)
72
48
100.0 %
0.40 [ 0.18, 0.88 ]
Total events: 26 (topical antibiotic), 28 (oral antibiotic) Heterogeneity: Chi2 = 8.51, df = 3 (P = 0.04); I2 =65% Test for overall effect: Z = 2.27 (P = 0.023)
0.01
0.1
10
100
Analysis 16.1. Comparison 16 Bullous impetigo; oral antibiotic versus another oral antibiotic, Outcome 1 cure/improvement.
Comparison: 16 Bullous impetigo; oral antibiotic versus another oral antibiotic Outcome: 1 cure/improvement
Study or subgroup
cephalexin n/N
dicloxacillin n/N
Weight
1 cephalexin versus dicloxacillin Dillon 1983 26/28 23/29 100.0 % 3.39 [ 0.62, 18.49 ]
Total (95% CI)

28
29
100.0 %
3.39 [ 0.62, 18.49 ]
Total events: 26 (cephalexin), 23 (dicloxacillin) Test for overall effect: Z = 1.41 (P = 0.16)
0.05
0.2
20
favours dicloxacilli
favours cephalexin
87
Analysis 17.1. Comparison 17 Secondary impetigo: steroid versus antibiotic, Outcome 1 cure/improvement.
Comparison: 17 Secondary impetigo: steroid versus antibiotic Outcome: 1 cure/improvement
Study or subgroup
steroid n/N
antibiotic n/N
Weight
1 betamethasone versus gentamycin Wachs 1976 15/27 8/27 100.0 % 2.97 [ 0.97, 9.12 ]
Total (95% CI)

27
27
100.0 %
2.97 [ 0.97, 9.12 ]
Total events: 15 (steroid), 8 (antibiotic) Test for overall effect: Z = 1.90 (P = 0.057)
0.1 0.2
0.5
10
favours antibiotic
favours steroid
Analysis 18.1. Comparison 18 Secondary impetigo: steroid+antibiotic versus steroid, Outcome 1 cure/improvement.
Comparison: 18 Secondary impetigo: steroid+antibiotic versus steroid Outcome: 1 cure/improvement
Study or subgroup
steroid+antibiotic n/N
steroid n/N
Weight
1 betamethasone+gentamycin versus betamethasone Wachs 1976 18/25 15/27 100.0 % 2.06 [ 0.65, 6.54 ]
Total (95% CI)

25
27
100.0 %
2.06 [ 0.65, 6.54 ]
Total events: 18 (steroid+antibiotic), 15 (steroid)
0.1 0.2
0.5
10
favours steroid
favours steroid+ab
88
Analysis 19.1. Comparison 19 Secondary impetigo: steroid+antibiotic versus antibiotic, Outcome 1 cure/improvement.
Comparison: 19 Secondary impetigo: steroid+antibiotic versus antibiotic Outcome: 1 cure/improvement
Study or subgroup
steroid+antibiotic n/N
antibiotic n/N
Weight
1 betamethasone+gentamycin versus gentamycin Wachs 1976 18/25 8/27 100.0 % 6.11 [ 1.84, 20.31 ]
Total (95% CI)

25
27
100.0 %
6.11 [ 1.84, 20.31 ]
Total events: 18 (steroid+antibiotic), 8 (antibiotic)
0.05
0.2
20
favours antibiotic
favours steroid+ab
Analysis 20.1. Comparison 20 Secondary impetigo: oral antibiotic versus another oral antibiotic, Outcome 1 cure/improvement.
Comparison: 20 Secondary impetigo: oral antibiotic versus another oral antibiotic Outcome: 1 cure/improvement
Study or subgroup
cephalexin n/N
enoxacin n/N
Weight
1 cephalexin versus enoxacin Fujita 1984 2/4 4/6 100.0 % 0.50 [ 0.04, 6.68 ]
Total (95% CI)

Total events: 2 (cephalexin), 4 (enoxacin) Heterogeneity: not applicable
100.0 %
0.50 [ 0.04, 6.68 ]
Test for overall effect: Z = 0.52 (P = 0.60)
0.05
0.2
20
favours enoxacin
favours cephalexin
89
APPENDICES Appendix 1. The Cochrane Skin Group Specialised Register (March 2002) search strategy
(impetig* or pyoderma or ((staphylococc* or streptococc*) and skin and infection*)) and (therap* or treatment* or intervention*)
Appendix 2. CENTRAL and National Research Register (Issue 1, 2002) search strategy
1. ((IMPETIG* or PYODERMA) OR (((STREPTOCOCC* or STAPHYLOCOCC*) and SKIN) AND INFECTION*)) 2. IMPETIGO*:ME (#1 or #2)
Appendix 3. MEDLINE (from 1966 to January 2003) search strategy

1. RANDOMIZED CONTROLLED TRIAL.pt. 2. CONTROLLED CLINICAL TRIAL.pt. 3. RANDOMIZED CONTROLLED TRIALS/ 4. RANDOM ALLOCATION/ 5. DOUBLE-BLIND METHOD/ 6. SINGLE-BLIND METHOD/ 7. OR/1-6 8. HUMAN.sh. 9. 7 AND 8 10. CLINICAL TRIAL.pt. 11. EXP CLINICAL TRIALS/ 12. (CLIN$ ADJ25 TRIAL$). ti,ab. 13. ((SINGL$ OR DOUBL$ OR TREBL$ OR TRIPL$) ADJ 3 (BLIND$ OR MASK$)). ti,ab. 14.PLACEBOS/ 15. PLACEBO$.ti,ab. 16. RANDOM$.ti,ab. 17. RESEARCH DESIGN/ 18. OR/9-17 19. COMPARATIVE STUDY.sh. 20. EXP EVALUATION STUDIES/ 21. FOLLOW UP STUDIES.sh. 22. PROSPECTIVE STUDIES.sh. 23. (CONTROL$ OR PROSPECTIV$ OR VOLUNTEER$).ti,ab. 24. OR/18-23 25. LIMIT 24 TO HUMAN 26. STAPHYLOCOCCAL SKIN INFECTIONS/ 27. IMPETIGO/ 28. IMPETIGO.ti,ab. 29. PYODERMA.ti,ab. 30. OR/26-29 31. 30 and 25
90
Appendix 4. EMBASE (from 1980 to March 2000) search strategy

1. exp clinical trial/ or exp randomized controlled trial/ 2. (clinical trial or randomized controlled trial).af. 3. exp controlled study/ or controlled clinical trial.mp. 4. random$.af. 5. exp double blind procedure/or exp placebo/ 6. Single blind procedure/ 7. (single-blind or double blind or placebo).af. 8. COMPARATIVE STUDY.mp. 9. evaluation stud$.af. 10. exp clinical trial/ or exp major clinical study/ or exp prospective study/ or Clinical study/ 11. (clinical trial or major clinical study or prospective study or Clinical study).mp. 12. (control$ or prospectiv$ or volunteer$).mp. [mp=title, abstract, heading word, trade name, manufacturer name] 13. or/1-12 14. limit 13 to human 15. Impetigo/ or impetigo.mp. 16. Staphylococcus infection/ 17. exp Skin infection/ 18. 16 and 17 19. (staphyl$ adj3 skin infect$).mp. [mp=title, abstract, heading word, trade name, manufacturer name] 20. 15 or 18 or 19 21. 20 and 14
Appendix 5. LILACS (November 2001) search strategy

impetigo
Appendix 6. The metaRegister of Controlled Trials search strategy

impetigo, pyoderma
WHATS NEW
Last assessed as up-to-date: 26 November 2002.
4 October 2008
Amended
Converted to new review format.
91
HISTORY
Protocol rst published: Issue 4, 2001 Review rst published: Issue 2, 2004
2 September 2004 4 January 2003 27 November 2002
New search has been performed Amended New citation required and conclusions have changed
Minor update New studies found but not yet included or excluded Substantive amendment
92
CONTRIBUTIONS OF AUTHORS
Conceiving the review SK, JCvdW, LvSS Designing the review SK, JCvdW, LvSS, CB, AM Coordinating the review SK Data collection for the review SK, JCvdW Developing search strategy JCvdW Undertaking searches JCvdW, SK Screening search results JCvdW, SK Organising retrieval of papers JCvdW, SK Screening retrieved papers against inclusion criteria LvSS, SK Appraising quality of papers JCvdW, AV Abstracting data from papers CB, AM Writing to trial authors of papers for additional information SK Obtaining and screening data on unpublished studies JCvdW, SK Data management for the review SK Entering data into RevMan SK Analysis of data SK Interpretation of data All authors Providing a methodological perspective JCvdW Providing a clinical perspective SK, CB Providing a policy perspective SK, CB Writing the review SK Providing general advice on the review All authors Securing funding for the review JCvdW Performing previous work that was the foundation of current study LvSS, JCvdW, SK
DECLARATIONS OF INTEREST
Three authors of this review are authors of one included trial (Sander Koning, Lisette WA van Suijlekom-Smit, Johannes C van der Wouden (Koning 2002)).
93
SOURCES OF SUPPORT Internal sources

Department of General Practice, Erasmus MC - University Medical Center Rotterdam, Netherlands.
External sources
No sources of support supplied
INDEX TERMS Medical Subject Headings (MeSH)

Administration, Oral; Administration, Topical; Anti-Bacterial Agents [ therapeutic use]; Impetigo [ drug therapy]; Randomized Controlled Trials as Topic
MeSH check words

Humans
94

Interventions of Impetigo

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Interventions of Impetigo

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Interventions for impetigo (Review)

Interventions for impetigo

Description of the condition

Description of the intervention

Types of outcome measures

How the intervention might work

Why it is important to do this review

Search methods for identication of studies OBJECTIVES

Criteria for considering studies for this review

Searching other resources

References from published studies

No language restrictions were applied.

Data collection and analysis

Assessment of methodological quality

Risk of bias in included studies

Arata 1989a Arata 1989b

+ Arredondo 1987 Barton 1987 Barton 1988 Barton 1989 +

Table 2. Delphi Quality Score

Table 2. Delphi Quality Score

Table 2. Delphi Quality Score

Arata 1989a Arata 1989b

Table 3. Jadad Quality Score

Table 3. Jadad Quality Score

Table 3. Jadad Quality Score

(ii) Oral antibiotics

Oral antibiotics versus placebo (one study)

(ii) Oral antibiotics

(c) Secondary impetigo

(iii) Disinfecting treatments

(i) Topical antibiotics

(b) Bullous impetigo

(ii) Oral antibiotics (i) Topical antibiotics

Table 4. Declared sponsorship or funding

Implications for topical antibiotics in clinical practice

Implications for use of systemic antibiotics in clinical practice

Implications for research

AUTHORS CONCLUSIONS Implications for practice

Implications for topical disinfectants in clinical practice

References to studies included in this review

References to studies excluded from this review

References to studies awaiting assessment

References to ongoing studies

Characteristics of included studies [ordered by study ID]

Risk of bias Item Allocation concealment? Authors judgement No Description C - Inadequate

Seven days, failure LTFU 6/35 (not evaluable) SE: NR

Item Allocation concealment? Beitner 1996 Methods

Authors judgement Unclear

Risk of bias Item Allocation concealment? Authors judgement No Description C - Inadequate

Risk of bias Item Allocation concealment? Authors judgement No Description C - Inadequate

Item Allocation concealment? Esterly 1991 Methods

Authors judgement Unclear

Item Allocation concealment? Gonzalez 1989 Methods

Authors judgement Unclear

Authors judgement Unclear

Authors judgement Unclear

Seven days, cured/improved SE: mild staining HC + h 2/24 HC + m 0/24

Item Allocation concealment?

Authors judgement Yes

LTFU: 0 SE: M: 0/30, E 6/30 (gastrointestinal)

Risk of bias Item Allocation concealment? Authors judgement No Description C - Inadequate

Risk of bias Item Allocation concealment? Authors judgement No Description C - Inadequate

Authors judgement Unclear

Item Allocation concealment? Park 1993 Methods

Authors judgement Unclear