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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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 i INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 94 ii [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. [email protected]. 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 superficial 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% confidence 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 significantly 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 efficacy. 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 fill 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 superficial bacterial skin infection, most frequently encountered in children. It is typically classified 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 classified 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 superficial 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 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 2 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. 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 inflammation 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 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, (flu)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. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 3 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. 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 conflict between what is in the best interest of the individual patient, and what would best benefit the community in terms of cost and induction of antibiotic resistance. Primary outcomes 1. Cure as defined 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 identification of studies OBJECTIVES To assess the effects of treatments for impetigo, including waiting for natural resolution. 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 confirmed 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 specific subgroup with impetigo could be identified, for which the results were separately described. Studies on secondary impetigo or impetiginised dermatoses were included. 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. Searching other resources Handsearching We handsearched the Yearbook of Dermatology (1938 to 1966) and the Yearbook of Drug Therapy (1949 to 1966). Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 4 References from published studies References from published studies, including secondary review articles, were checked for further studies. 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 defined 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 five 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 • • • • randomisation procedure; allocation concealment; intention-to-treat analysis; baseline comparison of severity of disease. 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 field 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 significant heterogeneity. Data synthesis Where there was no statistical evidence of heterogeneity we used fixed effect models to estimate effects. Otherwise, random effect models were used. Odds ratios with 95% confidence intervals were used as effect measures for dichotomous outcomes. Sensitivity analysis Prespecified 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 confirmation; 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 Two independent authors (JCvdW and AV) assessed the methodological quality of the trials. The following items were addressed: See: Characteristics of included studies; Characteristics of excluded studies. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 5 Results of the search Approximately 700 studies were identified, 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-five 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-five 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 defined. 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 specified, 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-five 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. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 6 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 Item D1a Was a method of randomisation performed? D1b Was the treatment allocation concealed? D2 Were the groups similar at baseline concerning the most important prognostic characteristics? D3 Were both inclusion and exclusion criteria specified? D4 Was the outcome assessor blinded? D5 Was the care provider blinded? D6 Was the patient blinded? D7 Were point estimates and measures of variability presented for primary outcome measures? D8 Did the analysis include an intention-to-treat-analysis? J1a Was the study described as randomised? J1b Is the method appropriate? J2a Was the study described as double blind? J2b Is the method appropriate? J3 Was there a description of withdrawals and drop-outs? Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 7 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 ? ? + ? ? ? ? + - 2 Arata 1989b + ? + ? ? ? ? + - 3 + - - + - - - + - 3 Barton 1987 + + ? + ? ? ? - - 3 Barton 1988 + + ? + ? ? ? - - 3 Barton 1989 + ? ? + - - - - - 2 Bass 1997 + ? - + + + + + - 6 Beitner 1996 + ? ? + ? ? ? + - 3 Blaszcyk 1998 + ? + + ? ? + + - 5 Britton 1990 + + + + + + + + - 8 Christensen 1994 + - - + - - - + + 4 Dagan 1989 + ? + - ? ? ? + - 3 Dagan 1992 + + + + + + + + - 8 Daniel 1991a (1st study) + ? ? + ? ? ? + - 3 Arredondo 1987 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 8 Table 2. Delphi Quality Score (Continued) Daniel 1991b (2nd study) + ? ? + ? ? ? + - 3 Demidovich 1990 + ? + + + + - + - 6 Dillon 1983 + ? ? + ? ? ? + - 3 Dux 1986 + - + + ? ? ? + - 4 Eells 1986 + ? ? + ? ? ? + - 3 Esterly 1991 + ? - - - - - + - 2 Fujita 1984 + ? - + + ? + + - 5 Gilbert 1989 + ? + + ? ? ? + - 4 Ginsburg 1978 + ? + - ? ? ? + - 3 Goldfarb 1988 + ? - + - - - + - 3 Gonzalez 1989 + ? + + + ? ? + - 5 Gould 1984 + ? - + ? ? ? + - 3 Gratton 1987 + ? ? - ? ? ? + - 2 Hains 1989 + ? ? + - - - + - 3 Jaffe 1985 + + + + ? ? + + - 6 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 9 Table 2. Delphi Quality Score (Continued) Jaffe 1986 + ? + - + + + + + 7 Kennedy 1985 + ? + + ? + + + - 6 Kiani 1991 + ? + + ? ? + + - 5 Koning 2002 + + + + + + + + + 9 Koranyi 1976 + + ? + + + ? + + 7 McLinn 1988 + ? + + ? ? ? + + 5 Mertz 1989 + - - + + - - + - 4 Montero 1996 + ? + + - - - + - 4 Moraes Barbosa 1986 + - + + - - - + - 4 Morley 1988 + ? + + + ? + + + 7 Nolting 1988 + ? + + ? ? ? + + 5 Park 1993 + ? ? + ? ? ? + - 3 Pruksachat. 1993 + ? ? + ? ? ? + - 3 Rice 1992 + ? + + - - - + - 4 Rodriguez 1993 + ? ? + - - - + - 3 Rojas 1985 ? - ? - ? + + + - 3 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 10 Table 2. Delphi Quality Score (Continued) Ruby 1973 + - + - ? ? - + - 3 Sutton 1992 + ? + + + + + + - 7 Tack 1997 + - + + + - - + - 5 Tack 1998 + ? ? + ? ? + + - 4 Tamayo 1991 + ? + + - - - + + 5 Tassler 1993 + - + + - - - + - 4 Vainer 1986 + ? ? + + + - + - 5 Wachs 1976 + ? ? + ? + + + - 5 Wainscott 1985 + ? ? - + + - + - 4 Welsh 1987 + ? + + - - - + - 4 White 1989 + ? + + + - - + - 5 Wilkinson 1988 + ? ? + - - - + - 3 Table 3. Jadad Quality Score Randomised? J1a randomised? J1b appropiate? J2a doubleblind? J2b appropiate? J3 withdrawal? Total score Arata 1989a ? ? + ? + 2 Arata 1989b + ? + ? ? 2 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 11 Table 3. Jadad Quality Score (Continued) Arredondo 1987 + ? - - - 1 Barton 1987 + + + ? + 4 Barton 1988 + + + ? ? 3 Barton 1989 + ? - ? - 1 Bass 1997 + + + + + 5 Beitner 1996 + ? - ? - 1 Blaszcyk 1998 + ? + + + 4 Britton 1990 + + + ? + 4 Christensen 1994 + + + - + 4 Dagan 1989 + + + - + 4 Dagan 1992 + + + + + 5 Daniel 1991a + + - - + 3 Daniel 1991b + + - - + 3 Demidovich 1990 + ? - - - 1 Dillon 1983 + + - ? + 3 Dux 1986 + ? - - + 2 Eells 1986 + + + ? + 4 Esterly 1991 + ? - ? + 2 Fujita 1984 + ? + ? + 3 Gilbert 1989 + ? + ? - 2 Ginsburg 1978 + ? - ? - 1 Goldfarb 1988 + ? - ? + 2 Gonzalez 1989 + ? + ? - 2 Gould 1984 + + + ? + 4 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 12 Table 3. Jadad Quality Score (Continued) Gratton 1987 + ? - ? - 1 Hains 1989 + ? - ? + 2 Jaffe 1985 + ? + + - 3 Jaffe 1986 + + + + + 5 Kennedy 1985 + ? + ? ? 2 Kiani 1991 + + + + + 5 Koning 2002 + + + + + 5 Koranyi 1976 + + - - + 3 McLinn 1988 + + - - + 3 Mertz 1989 + + - - + 3 Montero 1996 + ? - ? + 2 Moraes Barbosa + 1986 ? - - - 1 Morley 1988 + ? - ? - 1 Nolting 1988 + + + ? + 4 Park 1993 + ? - - - 1 Pruksachat. 1993 + ? - - ? 1 Rice 1992 + ? - - + 2 Rodriguez 1993 + ? - - + 2 Rojas 1985 ? ? + ? - 1 Ruby 1973 + + - - + 3 Sutton 1992 + + + ? + 4 Tack 1997 + ? - - + 2 Tack 1998 + - + + + 4 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 13 Table 3. Jadad Quality Score (Continued) Tamayo 1991 + ? - - + 2 Tassler 1993 + ? - - + 2 Vainer 1986 + + - - - 2 Wachs 1976 + ? + ? ? 2 Wainscott 1985 + + - - + 3 Welsh 1987 + ? - - + 2 White 1989 + + - - + 3 Wilkinson 1988 + ? + ? - 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 first 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). 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. (i) Topical antibiotics Topical antibiotics versus placebo (five studies) Overall topical antibiotics showed better cure rates or more improvement than placebo (odds ratio (OR) 6.49, 95% confidence 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). Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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. Topical antibiotics versus oral (systemic) antibiotics (sixteen studies) Pooling of ten studies which compared mupirocin with oral erythromycin showed significantly better cure rates or more improvement with mupirocin (OR 1.76, 95% CI 1.05 to 2.97; Analysis 3.1). However no significant differences were seen between mupirocin and dicloxacillin (Arredondo 1987), cephalexin (Bass 1997) or ampicillin (Welsh 1987). Fusidic acid was significantly 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 significantly 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 influence 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 benefit for mupirocin, but not to such a degree as the three good quality studies. Topical antibiotics versus disinfecting treatment (two studies) In one study (Ruby 1973), no statistically significant 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 significance (OR 1.79, 95% CI 0.99 to 3.25; Analysis 4.1). When the two studies were pooled, topical antibiotics were significantly better than disinfecting treatments (OR 1.84, 95% CI 1.03 to 3.29; Analysis 4.1). (ii) Oral antibiotics Oral antibiotics versus placebo (one study) A single study (Ruby 1973) was inconclusive, detecting no significant 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 significant difference in favour of cefuroxim (OR 6.40, 95% CI 1.44 to 28.44; Park 1993; Analysis 6.1). Oral antibiotic versus another oral antibiotic: one cephalosporin versus another cephalosporin (four studies) No significant 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 significant 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). 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 fleroxacin in another study (Tassler 1993), no significant difference was seen (OR 1.68, 95% CI 0.37 to 7.63; Analysis 10.1). Cloxacillin was significantly superior to penicillin in two studies (Gonzalez 1989; Pruksachat. 1993: (pooled OR 13.74, 95% CI 4.36 to 43.24; Analysis 10.1). Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 15 Other comparisons of oral antibiotics (one study) (ii) Oral antibiotics In a single small study (Arata 1989b), no difference in cure rates/ improvement could be detected between lomefloxacin and norfloxacin (OR 2.50, 95% CI 0.37 to 16.89; Analysis 11.1). Oral antibiotic versus another oral antibiotic (one study) Oral antibiotics versus disinfecting treatments (one study) No significant difference was seen between cephalexin and dicloxacillin (Dillon 1983; OR 3.39, 95% CI 0.62 to 18.49; Analysis 16.1). 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) Antibiotic versus steroid versus antibiotic plus steroid (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. (b) Bullous impetigo In a three-armed study (Wachs 1976), the combination of betamethasone and gentamycin cream was significantly 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 significant differences (Analysis 17.1; Analysis 18.1). (ii) Oral antibiotics (i) Topical antibiotics Topical antibiotics versus other topical antibiotics (one study, three comparisons) In a small study (Moraes Barbosa 1986), fusidic acid was significantly 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). In a very small study, no difference was detected between cephalexin and enoxacin (Fujita 1984) (Analysis 20.1). 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 first (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 significantly 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 significant 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 specified) 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). Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 16 (iii) Oral treatments (b) Antibiotics (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). 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 flucloxacillin 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). (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. 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). Table 4. Declared sponsorship or funding Study Sponsor (product) Barton 1987 Fleur de Lis Foundation Barton 1988 Warner-Lambert Corporation Barton 1989 Warner- Lambert Corporation Beitner 1996 Bristol-Myers Squibb (cefadroxil) Blaszcyk 1998 Pharmacia & Upjohn Asia (clindamycin) Britton 1990 US Navy Bureau of Medicine and Surgery Clinical Investigation Program Daniel 1991a; Daniel 1991b Pfizer Central Research (azithromycin) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 17 Table 4. Declared sponsorship or funding (Continued) Dillon 1983 Eli Lilly Research (cephalexin) Goldfarb 1988 Beecham Laboratories (mupirocin) Hains 1989 Bristol-Myers Squibb (cefadroxil) Jaffe 1985 Beecham Laboratories (amoxicillin+clavulanic acid) Koning 2002 Dutch College of General Practitioners Mertz 1989 Beecham Laboratories (mupirocin) Sutton 1992 Leo Laboratories (fusidic acid) Tack 1997 Parke-Davis pharmaceutical research (cefdinir) Tack 1998 Parke-Davis pharmaceutical research (cefdinir) Wainscott 1985 Beecham Pharmaceuticals (mupirocin) White 1989 Beecham Pharmaceuticals (mupirocin) 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, significant differences became insignificant 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 day). Cure rates of specific 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. 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 five 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 significantly less effective (cure rate 72% versus 82%) than fusidic acid in a relatively large Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 finding 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 finding 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 reflect 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. AUTHORS’ CONCLUSIONS Implications for practice Implications for topical disinfectants in clinical practice 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 efficacy, no clear preference can be given for B-lactamase resistant narrow-spectrum penicillins such as cloxacillin, dicloxacillin and flucloxacillin, 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 insufficient evidence to say whether oral antibiotics are better than topicals for more serious and extensive forms of impetigo. From a practical standpoint, oral antibiotics might be an easier option for people with very extensive impetigo. Implications for research Trials should compare treatments for a specific disease, rather than the effectiveness of a specific 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 specific 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 efficacy 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: Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 19 • 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 defining clinical cure could be absence of crusts, dryness, intactness, and absence of redness of skin. A parameter of improvement could be ’size of affected surface’. Choosing ’standard’ follow-up periods, 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;37:1016–42. Arata 1989b {published data only} Arata J, Yamamoto Y, Tamaki H, Okawara A, Fukaya T, Ishibashi Y. Double-blind study of lomefloxacin versus norfloxacin in the treatment of skin and soft tissue infections. Chemotherapy 1989;37: 482–503. Arredondo 1987 {published data only} Arredondo JL. Efficacy and tolerance of topical mupirocin compared with oral dicloxacillin in the treatment of primary skin infections. Current Therapeutic Research 1987;41(1):121–7. Barton 1987 {published data only} Barton LL, Friedman AD. Impetigo: A reassessment of etiology and therapy. Pediatric Dermatology 1987;4:185–8. Barton 1988 {published data only} Barton LL, Friedman AD, Portilla MG. Impetigo contagiosa: a comparison of erythromycin and dicloxacillin therapy. Pediatric Dermatology 1988;5:88–91. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 20 Barton 1989 {published data only} Barton LL, Friedman AD, Sharkey AM, Schneller DJ, Swierkosz EM. Impetigo Contagiosa III. Comparative efficacy of oral erythromycin and topical mupirocin. Pediatric Dermatology 1989;6 (2):134–8. 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;16:708–9. Beitner 1996 {published data only} Beitner H. Cefadroxil compared with flucloxacillin for skin and soft tissue infection. Journal of Dermatological Treatment 1996;7(3): 143–6. 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):341–53. 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;117:827–9. 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;74:460–2. 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;143:916–8. 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;36:287–90. 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;19:433–45. 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):177–81. 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):933–40. 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;122:1273–6. Esterly 1991 {published data only} Esterly NB, Markowitz M. The treatment of pyoderma in children. Journal of the American Medical Association 1970;212:667–70. 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 superficial suppurative skin and soft tissue infections. A double blind study in comparison with cephalexin compound granules (LKeflex). Chemotherapy 1984;32:728–53. 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;20:1083–7. 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):845–8. Goldfarb 1988 {published data only} Goldfarb J, Crenshaw D, O’Horo J, Lemon E, Blumer JL. Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo. Antimicrobial Agents and Chemotherapy 1988;32(12):1780–3. 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: 127–41. 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;80:85–93. 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):472–3. 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;19:433–45. Hains 1989 {published data only} Hains CS, Johnson SE, Nelson KG. Once-daily cefadroxil therapy for pyoderma. Pediatric Infectious Disease Journal 1989;8(9):648–9. 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;144:1313–5. Jaffe 1985 {published data only} Jaffe AC, O’Brien 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):160–8. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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; 4:628–36. 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: 79–83. 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;10:880–4. 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;324:203–06. 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):368–70. McLinn 1988 {published data only} McLinn S. A bacteriologically controlled, randomized study comparing the efficacy 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):883–5. ∗ McLinn S. Topical mupirocin versus systemic erythromycin treatment for pyoderma. The Pediatric Infectious Disease Journal 1988;7(11):785–90. 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):1069–73. ∗ 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;125:1069–73. Montero 1996 {published data only} Montero L. A comparative study of the efficacy, 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):125–31. 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 estafilococico do recem–nascido]. Arquivos Brasileiros de Medicina 1986;60(6):509–11. Morley 1988 {published data only} Morley PAR, Munot LD. A comparison of sodium fusidate ointment and mupirocin ointment in superficial skin sepsis. Current Medical Research Opinion 1988;11:142–8. 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;27:716–9. 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;31:312–9. 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): 222–9. 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):210–4. Rodriguez 1993 {published data only} Rodriguez-Solares A, Pérez-Gutiérrez F, Prosperi J, Milgram E, Martin A. A comparative study of the efficacy, safety and tolerance of azithromycin, dicloxacillin and flucloxacillin in the treatment of children with acute skin and skin-structure infections. Journal of Antimicrobial Chemotherapy 1993;31(suppl E):103–9. Rojas 1985 {published data only} ∗ Rojas R, Eells L, Eaglstein W, Provanetti Y, Mertz PM, Mehlisch DR, et al.The efficacy 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. 1985:96–102. Rojas R, Zaias N. The efficacy 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. 1985:150–4. Ruby 1973 {published data only} Ruby RJ, Nelson JD. The influence of hexachlorophene scrubs on the response to placebo or penicillin therapy in impetigo. Pediatrics 1973;52:854–9. Sutton 1992 {published data only} Sutton JB. Efficacy and acceptability of fusidic acid cream and mupirocin ointment in facial impetigo. Current Therapeutic Research 1992;51(5):673–8. 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: 739–42. Tack 1998 {published data only} Tack KJ, Littlejohn TW, Mailloux G, Wolf MM, Keyserling CH. Cefdinir adult skin infection study group. Cefdinir versus Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 22 cephalexin for the treatment of skin and skin-structure infections. Clinical Therapeutics 1998;20(2):244–56. 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 mupirocín tópicos en el tratamiento del impétigo]. Dermatología Revista Mexicana 1991;55:99–103. Tassler 1993 {published data only} Tassler H. Comparative efficacy and safety of oral fleroxacin and amoxicillin/clavunalate potassium in skin and soft-tissue infections. The American Journal of Medicine 1993;94 Suppl 3A:159–165. 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;148:1202–6. 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):323–8. 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. 1985:137–140. 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):114–20. White 1989 {published data only} White DG, Collins PO, Rowsell RB. Topical antibiotics in the treatment of superficial skin infections in general practice - a comparison of mupirocin with sodium fusidate. Journal of Infection 1989;18:221–9. 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):514–5. 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):20–2. Anonymous 1998 {published data only} Anonymous. Cefdinir - A new oral Cephalosporin. The Medical Letter 1998;40(1034):85–7. 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):1443–60. 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 study of SY 5555 versus cefaclor in the treatment of skin and skin structure infections. Chemotherapy 1994;42:740–60. Arosemena 1977 {published data only} ∗ Arosemena R, Bogaert H, Bonilla Dib E, Close de León J, Corrales H, Delgado Mayorga S, et al.Double blind study comparing preparations for topical application [Ensayo doble ciego entre preparaciones combinadas para aplicación tópica]. Investigación Médica Internacional 1977;4:502–8. Azimi 1999 {published data only} Azimi PH, Barson WJ, Janner D, Swanson R and the Unasyn Pediatric Study Group. Efficacy 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):609–13. Baldwin 1981 {published data only} Baldwin RJT, Cranfield R. A Multi-Centre General practice Trial Comparing Fucidin Ointment and Fucidin Cream. The British Journal of Clinical Practice 1981;35(4):157–60. 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: 143–7. Bastin 1982 {published data only} Bastin R, Rapin M, Kernbaum S. Controlled study of pristinamycin versus oxacillin in staphylococcal infections. Pathologie et Biologie 1982;30:473–5. 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 superficial pyoderma [Pristinamycine (Pyostacine 500) versus Oxacilline (Bristopen) dans le traitement des pyodermites superficielles]. Annales de Dermatologie et de Venereologie 1997;124:394–9. 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):60–3. Burnett 1963 {published data only} Burnett WJ. The route of antibiotic administration in superficial impetigo. The New England Journal of Medicine 1963;268:72–5. 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):153–5. 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 antibactérien topique, la mupirocine, par rapport à un placebo dans le traitement des infections de la peau et des tussus mous]. Pharmatherapeutica 1988;5(198):198–203. 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;4:176–8. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 23 Dillon 1970 {published data only} Dillon HC. The treatment of streptococcal skin infections. The Journal of Pediatrics 1970;76(5):676–84. Harding 1970 {published data only} Harding JW, Path MRC. Flucloxacillin in the treatment of skin and soft-tissue infections. The Practioner 1970;205:801–6. Dillon 1979 {published data only} Dillon HC, Gray BM, Ware JC. Clinical and laboratory studies with cefaclor: efficacy in skin and soft-tissue infections. Postgraduate Medical Journal 1979;55 Suppl 4:77–81. 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):131–3. 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 ofloxacin 400 mg twice daily in skin and soft-tissue infections. Chemotherapy 1997;43:378–84. 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;36:1614–8. 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 superficial bacterial infection of the skin. The Journal of International Medical Research 1990;18:89–93. Esterly 1970 {published data only} Esterly NB, Markowitz M. The Treatment of Pyoderma in Children. JAMA 1970;212(10):1667–70. 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;119:76–8. 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;9:63–6. 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): 679–81. Jennings 1999 {published data only} Jennings MB, Alfieri D, Kosinski M, Weinberg JM. An investigator-blind study of the efficacy 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):68–72. Keeny 1979 {published data only} Keeney RE, Seamans ML, Russo RM, Gururaj VJ, Alle JE. The comparative efficacy of minocycline and penicillin-V in Staphylococcus aureus skin and soft-tissue infections. Therapeutics for the Clinician 1979;23:711–8. Kumakiri 1988 {published data only} Kumakiri M, Yasui C, Ohkawara A. Clinical study on TE-031 tablet in dermatology. Chemotherapy 1988;36:935–7. 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):882–5. Forbes 1952 {published data only} Forbes MA. A clinical evaluation of neomycin in different bases. Southern Medical Journal 1952;45(3):235–9. 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):115–21. Golcman 1997 {published data only (unpublished sought but not used)} Golcman B, Tuma SR, Golcman R, Schalka S, Gonzalez MA. Efficacy and safety of cefprozil and cefaclor on cutaneous infections. Anais Brasileiros de Dermatologia 1997;72(1):79–82. Lentino 1984 {published data only} Lentino JR, Stachowski M, Strikas R, Parrillo P. Comparative efficacy of cefotiam versus cephalotin in the therapy of skin and soft-tissue infections. Antimicrobial Agents and Chemotherapy 1984; 25(6):778–80. Goldfarb 1987 {published data only} Goldfarb J, Aronoff SC, Jaffe A, Reed MD, Blumer JL. Sultamicillin in the treatment of superficial skin and soft tissue infections in children. Antimicrobial Agents and Chemotherapy 1987;31:663–4. Levenstein 1982 {published data only} Levenstein JH. Efficacy and tolerability of an amoxycillin/ clavulanic acid combination in the treatment of common bacterial infections. Sa Mediese tydskrif 1982;62:16–20. 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;18:336–43. 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;16:103–8. Hanfling 1992 {published data only} Hanfling MJ, Hausinger SA, Squires J. Loracarbef versus cefaclor in pediatric skin and skin structure infections. The Pediatric Infectious Disease Journal 1992;11 Suppl 8:27–30. 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: 46–56. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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;22:63–9. 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 efficacy and toxicity of local fusidic aid versus oral dicloxacillin in infections of the skin [Evaluacion de la eficacia y toxicidad del acido fusidico local frente a dicloxacilina oral en infecciones de la piel]. Medicina cutanea ibero-latino-americana 1988;16:171–3. 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:36–9. 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:80–5. terbinafine cream and 0.1% gentamicin sulphate cream in pyoderma. British Journal of Dermatology 1992;126(39):56–60. 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):82–6. 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;15:87–92. 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;34:567–70. Parish 1991 {published data only} Parish LC, Jungkind DL. Systemic antimicrobial therapy in skin and skin structure infections: comparison of temafloxacin and ciprofloxacin. The American Journal of Medicine 1991;91 Suppl 6A:115–119. McMillan 1969 {published data only} McMillan R, Hurwitz R. Tropical bacterial pyoderma in Vietnam. JAMA 1969;210(9):1734–6. 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):342–8. Milidiú d Silva 1985 {published data only} Milidiú 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. 1985:162–5. 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):856–9. 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):1137–63. Powers 1991 {published data only} Powers RD, Schwartz R, Snow RM, Yarbrough III DR. Ofloxacin versus cephalexin in the treatment of skin, skin structure, and softtissue infections in adults. Clinical Therapeutics 1991;13(6): 727–36. Neldner 1991 {published data only} Neldner KH. Double-blind randomized study of oral temafloxacin and cefadroxil in patients with mild to moderately severe bacterial skin infections. The American Journal of Medicine 1991;91 Suppl 6A:111–4. Nichols 1997 {published data only} Nichols RL, Smith JW, Gentry LO, Gezon J, Campbell T, Sokol P, et al.Multicenter, randomized study comparing levofloxacin and ciprofloxacin for uncomplicated skin and skin structure infections. Southern Medical Journal 1997;90(12):1193–200. Powers 1993 {published data only} Power RD. Open trial of oral fleroxacin versus amoxicillin/ clavulanate in the treatment of infections of skin and soft tissue. The American Journal of Medicine 1993;94 Suppl:155–8. 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;81:468–70. Nolting 1992 {published data only} Nolting S, Bräutigam M. Clinical relevance of the antibacterial activity of terbinafine: a contrallateral comparison between 1% 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):236–41. 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): 747–53. 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;16:205–10. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 pädiatrischen Praxis]. Schweizerische Rundschau fur Medizin Praxis / Revue suisse de medecine Praxis 1972;61(33):1051–2. Schupbach 1992 {published data only} Schupbach CW, Olovich KG, Dere WH. Efficacy of cefaclor AF in the treatment of skin and skin structure infections. Clinical Therapeutics 1992;14(3):470–9. 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: 91–5. 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. 1985:130–6. Smith 1993 {published data only} Smith JW, Nichols RL. Comparison of oral fleroxacin with oral amoxicillin/clavulanate for treatment of skin and soft-tissue infections. The American Journal of Medicine 1993;94:150–4. 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): 204–7. 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: 113–29. 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;42:51–6. Urbach 1966 {published data only} Urbach F. Combined chemotherapy in the treatment of superficial bacterial infections of the skin. Current Therapeutic Research 1966;8 (4):199–202. 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):339–45. 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):69–80. Wolbling 1987 {published data only} Wölbling RH, Schäfer 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 quarternären Ammoniumsalz]. Arzneimittelforschung 1987;37(2):218–20. 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;30:380–3. 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):1517–37. References to studies awaiting assessment Ciftci 2002 {published data only} Ciftci E, Guriz H, Aysev AD. Mupirocin vs terbinafine in impetigo. Indian Journal of Pediatrics 2002;29(9):679–82. [MEDLINE: 12356219] Claudy 2001 {published data only} Claudy A, Groupe Francais d’Etude. Superficial pyoderma requiring oral antibiotic therapy [Pyodermites superficielles necessitant une antibiotitherapie orale. Acide fusidique versus pristinamycine]. La Presse Medicale 2001;30(8):364–8. 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):566–6. Parish 2000 {published data only} Parish LC, Routh HB, Miskin B, Fidelholtz J, Werschler P, Heyd A, et al.Moxifloxacin versus cephalexin in the treatment of uncomplicated skin infections. International Journal of Clinical Practice 2000;54(8):497–503. References to ongoing studies McLinn 1988b {published data only} McLinn S. A bacteriologically controlled, randomized study comparing the efficacy 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):883–5. Additional references Baltimore 1985 Baltimore RS. Treatment of impetigo: a review. Pediatric Infectious Diseases 1985;4:597–601. 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 [NHG–Standaard bacteriële huidinfecties]. Huisarts Wet 1999;41:427–37. Britton 1990 Britton JW, Fajrdo JE, Krafte-Jacobs B. Comparison of mupirocin and erythromycin in the treatment of impetigo. Journal of Pediatrics 1990;117:827–9. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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, 1993:22–35. Carruthers 1988 Carruthers R. Prescribing antibiotics for impetigo. Drugs 1988;36: 364–9. 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;36:287–90. Dagan 1993 Dagan R. Impetigo in childhood: changing epidemiology and new treatments. Pediatric annals 1993;22:235–40. 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;41:93–101. Dillon 1979 Dillon HC. Post-streptococcal glomerulonephritis following pyoderma. Review of Infectious Diseases 1979;1:935–43. Espersen 1998 Espersen F. Resistance to antibiotics used in dermatological practice. British Journal of Dermatology 1998;139:4–8. Hay 1998 Hay RJ, Adriaans BM. Bacterial infections. In: Champion RH Burton JL, Ebling FJG editor(s). Textbook of Dermatology. 6th Edition. Oxford: Blackwell, 1998:1109–11. 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;17:1–12. Jadad 1998 Jadad AR, Moher D, Klassen TP. Guides for reading and interpreting systematic reviews: II How did the authors find the studies and assess their quality?. Archives of Paediatrics and Adolescent Medicine 1998;152:812–7. Kristensen 1991 Kristensen JK. Scabies and pyoderma in Lilongwe, Malawi: Prevalence and seasonal fluctuation. International Journal of Dermatology 1991;30:699–702. MacKenna MacKenna RMD, Cooper-Willis ES. Impetigo in the army, treated with microcrystalline sulphathiazole. Lancet 1945;269:357–8. 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, 2000:369–72. Ruby 1973 Ruby RJ, Nelson JD. The influence of hexachlorophene scrubs on the response to placebo or penicillin therapy in impetigo. Pediatrics 1973;52:854–9. 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;143:1140–3. 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;12:1235–41. ∗ Indicates the major publication for the study Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 27 CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID] Arata 1989a Methods time NR Japan Range (13/265) Participants Age 15 to 82 yrs, M/F 150/115 (all participants) mainly S.aureus Interventions cefdinir 100 mg, 3 td cefaclor 250 mg, 3 td Outcomes Ten days, excellent/good/poor Notes SE: (all participants) cefdinir 9/142 cefaclor 4/145 (mainly gastrointestinal) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Arata 1989b Methods time NR Japan Range (18/259) Participants All ages, M/F 152/97 mainly S.aureus (data for all participants) Interventions lomefloxacin 200 mg, 3 td norfloxacin 200 mg, 3 td Outcomes seven days, cured/improved Notes SE: (all participants) L 6/144, N 5/135 mainly gastrointestinal Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 28 Arata 1989b (Continued) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Arredondo 1987 Methods time NR Mexico city, Mexico Range (55/61) Participants average age seven yrs, M/F 30/31 S.aureus 67% Interventions mupirocin ointment 2%, 3 td, 5 to 10 days dicloxacillin 250 mg, 4 td, 5 to 10 days Outcomes Ten days, cure Notes open trial. LTFU 2/55 (1 in both groups) SE: M: nil reported D: abdominal pain 1/ 31, vomiting 2/31 Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Barton 1987 Methods 1986 June to August Missouri USA outpatients only impetigo Participants Children (age NR), M/F 29/32 S.aureus 35/65 Streptococcus 2/65 Both 30% PE Interventions penicillin V 50 mg/kg/day in 4 dd, 10 ds erythromycin 40 mg/kg/day in 4 dd, 10 ds Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 29 Barton 1987 (Continued) Outcomes Seven days, failure Notes LTFU 6/35 (“not evaluable”) SE: NR Risk of bias Item Authors’ judgement Description Allocation concealment? Yes A - Adequate Barton 1988 Methods 1987 June to August Missouri USA outpatients only impetigo Participants 2 m to 16 yrs, M/F 55/45 S. aureus 46/100, S. pyogenes 9/100, both 25/199. PE Interventions erythromycin 40 mg/kg/day in 4 dd, 10 ds dicloxacillin 25 mg/kg /day in 4 dd, 10 ds Outcomes Five to seven days, cure+improved Notes 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 Risk of bias Item Authors’ judgement Description Allocation concealment? Yes A - Adequate Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 30 Barton 1989 Methods 1988 June to August Missouri USA outpatients only impetigo Participants 3 m to 16 yrs M/F 49/48 S. aureus 80% PNE Interventions erythromycin 40 mg/kg/day in 3 dd, 7 days mupirocin ointment 2%, 3 td, 7 days Outcomes Four to seven days, cured + improved Notes LTFU: 1/97 non-bullous and 14% bullous SE: gastrointestinal: E 8/48, M 4/49 Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Bass 1997 Methods time NR Honolulu, Hawaii Hospital outpatients only impetigo Participants average age 3.8 yrs, sex NR S. aureus 41/48 PNE Interventions 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 Outcomes Eight to ten days, cure Notes LTFU 6/32, 5 in mupirocin group SE: not reported Risk of bias Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 31 Bass 1997 (Continued) Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Beitner 1996 Methods Dec 1992 to Nov 1994 25 centres, Sweden outpatients Range (60/327) Participants 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 Interventions cefradoxil 40 mg/kg/day, 10 days flucloxacillin tablets 750 mg, 2 td, or susp 30 to 50 mg/kg/day in 2 to 3 dd, 10 days Outcomes 10 to 12 days, cure/improved/failed Notes 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) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Blaszcyk 1998 Methods 1996 to 1997? Multicenter; Europe, Latin America and Asia. Range (42/539) Participants 16 to 70 yrs (all participants) PNE Interventions clindamycin caps 150 mg, 4 td clindamycin caps 300 mg, 2 td dicloxacillin caps 250 mg, 4 td Outcomes Seven days, cure Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 Authors’ judgement Description Allocation concealment? Unclear B - Unclear Britton 1990 Methods Oct 1988 to Oct 1989 Portsmouth Virginia USA outpatients only impetigo Participants 2 months to 12 yrs, M/F 27/17 S. aureus 26/48 PNE Interventions erythromycin 40 mg/kg/day in 4 dd + placebo cream mupirocin ointment 2%, 3 td + placebo susp. Outcomes Ten days, cured + improved Notes LTFU: E: 4/30, M: 2/24 SE minor gastrointestinal SE: 11 total, equally divided Risk of bias Item Authors’ judgement Description Allocation concealment? Yes A - Adequate Christensen 1994 Methods time NR Sweden, Germany, UK Outpatients (Germany) and GP (UK), both (Sweden) only impetigo Participants 3 + yrs. M/F131/125 S.aureus 199/256, S.pyogenes 21/256, both 36/256 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 33 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 Outcomes evaluation time NR, cure Notes 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 Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Dagan 1989 Methods May to October 1987 Negev region, Israel Outpatients only impetigo Participants 6 m to 9 yrs, sex NR S. aureus 37/51, S. pyogenes 14/51 PE Interventions 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 Outcomes Five days, cure +improved Notes 4/26 (amox) and 3/25 (amox/clav) participants missing from data of first follow-up moment SE: vomiting amox 1 amox/clav 0 diarrhoea amox 1 amox/clav 0 Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear D - Not used Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 34 Dagan 1992 Methods July 1989 to Oct 1990 Negev region, Israel outpatients only impetigo (bullous and non-bullous) Participants < 16 yrs, M/F 56/46 S. aureus 90/102, streptococci 1/3 of participants PNE Interventions erythromycin susp. 50 mg/kg/day 3td + placebo ointment, 7 days mupirocin ointment 2% 3td + oral placebo susp., 7 days Outcomes Seven days, failed Notes LTFU 8/51 E, 5/51 M SE: gastrointestinal E 11/47 M 4/51 Risk of bias Item Authors’ judgement Description Allocation concealment? Yes A - Adequate Daniel 1991a Methods 1987 to 1991 Belgium/France/FRG/ Netherlands/Norway/UK setting unclear Range (69/308) Participants 16 to 80 yrs All participants: S. aureus 195/308, streptococci 59/308 PNE Interventions azithromycin 250 mg twice (day 1),once daily (day 2 to 5), 5 days erythromycin 500 mg 4 td, 7 days Outcomes 11 to 16 days, cured Notes LTFU:azithromycin 1/36 erythromycin 2/33 SE: no subgroup data Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 35 Daniel 1991a (Continued) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Daniel 1991b Methods 1987-1989 Belgium/Germany/Ireland/UK setting unclear Range (17/323) Participants adults 17 to 90 yrs All participants: S aureus 158/323, streptococci 41/323 PNE Interventions azithromycin 250 mg twice (day 1),once daily (day 2 to 5), 5 days cloxacillin 500 mg, 4 td, 7 days Outcomes 11 to 16 days, cured/improved/failed Notes LTFU azithromycin 0/10 cloxacillin 1/7 SE: no subgroup data Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Demidovich 1990 Methods time NR Honolulu, Hawaii outpatients only impetigo Participants 5 m to 15 yrs. average 3 yrs S. aureus 45/73, GABHS 6/73, both 14/73, PNE Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 Outcomes Eight to ten days, failed Notes LTFU: 2 of 75 not available for follow-up SE: nil reported Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Dillon 1983 Methods 1980 summer/fall Alabama/USA outpatients only impetigo (bullous impetigo 57/70) Participants average age 3.2 yrs, MF 41/37 S. aureus: 64/70 PNE Interventions 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) Outcomes Prompt cure Notes LTFU: C: 5/40, D: 3/38 Bullous impetigo SE: NR Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 37 Dux 1986 Methods time NR Toronto, Canada setting unclear Range (36/149) Participants average age 22 yrs. M/F 81/68 bacterial culture results unclear PNE Interventions mupirocin ointment 2%, 3 td, 7 days eythromycin 250 mg, 4 td, 7 days cloxacillin 250 mg, 4 td, 7 days Outcomes Seven days, cure/improved/failure: C no participants with impetigo allocated Notes 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 Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Eells 1986 Methods Oct to Nov 1983 Puerto Rico outpatients only impetigo Participants 7 m to 13 yrs, M/F 13/25 mainly S.aureus PE Interventions mupirocin ointment 2%, 3 td, 7 to 9 days vehicle control, 3 td, 7 to 9 days Outcomes Eight days, cure/improved/failure: (one participant with ecthyma excluded in each group) Notes LTFU: M: 8/26, V: 6/26 SE: NR Risk of bias Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 38 Eells 1986 (Continued) Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Esterly 1991 Methods time NR Milwaukee Wisconsin USA outpatients only impetigo Participants 3 m to 14 yrs, average 4.3 yrs S.aureus 33% GABHS 12% both 41%. Part excluded: NR Interventions mupirocin (dose NR) erythromycin (dose NR) Outcomes time of evaluation NR, failure Notes 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 Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Fujita 1984 Methods time NR Japan outpatients Range (10/204) Participants Age 16 to 84 yrs M/F 120/84 (all participants) Interventions enoxacin 500 mg, 3 td cephalexin 500 mg 2 td (double dummy) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 39 Fujita 1984 (Continued) Outcomes after ... cured/improved Notes LTFU 20/224 SE (all participants): E 11 of 113, C 4 of 110 (mainly gastrointestinal) Secondary impetigo Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Gilbert 1989 Methods time NR Quebec Canada outpatients Range (19/70) Participants Age NR S. aureus 41/70 Streptococci 22/70 (all pat.) PE Interventions mupirocin ointment 2%, 3 td, 7 days fusidic acid cream 2%, 3 td, 7 days Outcomes Seven days, cure/improved/failure Notes LTFU: nil in impetigo groups SE nil recorded in either group Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Ginsburg 1978 Methods time NR Dallas, Texas, USA outpatients only impetigo Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 Interventions penicillin G 30 mg/kg/day in 4 dd, duration NR cefadroxil 45 mg/kg/day in 3 dd, duration NR Outcomes Eight days, cured + improved Notes LTFU 21/71 SE: one child removed from cefadroxil group because of vomiting, no other SE reported Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Goldfarb 1988 Methods time NR Cleveland Ohio USA outpatients only impetigo Participants 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 Interventions mupirocin ointment 2%, 3 td, 8 days erythromycin 40 mg/kg/day in 4 dd, 8 days Outcomes Eight days, cured/failed Notes LTFU M 1/30, E 3/32 SE: M 0/30, E: 5/30 mild diarrhoea Risk of bias Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 41 Goldfarb 1988 (Continued) Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Gonzalez 1989 Methods 1980 July to Sept Florida USA outpatients only impetigo (bullous and non-bullous). Participants 6 m to 12 yrs participants excluded if no S. aureus present Interventions penicillin V Potassium 50 mg/kg/day, in 4 dd, 10 days cloxacillin sodium 50 mg/kg/day, in 4 dd, 10 days Outcomes Ten days: cured + improved Notes LTFU: P 1/44, C 10/43 SE: NR Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Gould 1984 Methods time NR Edinburgh UK general practice Range (39/107) Participants Average age 18.7 (all participants) S. aureus 90/129, streptococci 32/129 (all participants) PNE Interventions mupirocin ointment 2%, once daily, until cleared placebo cream, once daily, until cleared Outcomes time of evaluation NR cure/improved/failure Notes LTFU M 3/17, P 1/22 SE NR Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 42 Gould 1984 (Continued) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Gratton 1987 Methods time NR Montreal Quebec Canada outpatients Range (15/60) Participants Age/sex NR S. aureus approx. 50% Part. excluded: NR Interventions mupirocin ointment 2%, 3 td, 7 days erythromycin 250 mg, 4 td, 7 days Outcomes Seven days, cure/improved/failure Notes SE not presented for impetigo patients Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Hains 1989 Methods 1986 summer Birmingham Alabama US outpatients child hospital only impetigo Participants 1 to 18 yrs, sex NR S. aureus 35%, GABHS 12% both 54% part. excluded: NR Interventions 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 Outcomes 14 days, cured Notes SE: nil reported Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 43 Hains 1989 (Continued) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Jaffe 1985 Methods time NR Cleveland Ohio USA outpatients child clinic Range (32/42) Participants 6 m to 12 yrs, ave to age 4.8 yrs S. aureus 33/36, S. pyogenes 8/36 PNE Interventions amoxicillin/clavulanic acid, eq. 20 mg/kg/day in 3 dd, 10 days cefaclor 20 mg/kg/day in 3 dd. Outcomes Ten days, cured/failed Notes SE: mild diarrhoea: A/C 2/18, C 5/16 (all participants) Risk of bias Item Authors’ judgement Description Allocation concealment? Yes A - Adequate Jaffe 1986 Methods time NR Multicenter, Wessex UK general practice Range (43/119) Participants 2,5 yrs to 83 yrs, median 14 to 16 yrs M/F 23/20. S. aureus 16/34, S. pyogenes 5/34. PNE Interventions 1% hydrocortisone + 0.5% potassium hydroxyquinoline sulphate cream, 2 td, 14 days 1% hydrocortisone + 2% miconazole nitrate cream, 2 td, 14 days Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 44 Jaffe 1986 (Continued) Outcomes Seven days, cured/improved Notes SE: mild staining HC + h 2/24 HC + m 0/24 Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Kennedy 1985 Methods time NR Bristol UK general practice only impetigo Participants average age 11 yrs (mupirocin), 17 yrs (Neomycin). M/F 2/1. S. aureus 23/34, S. pyogenes 10/34. PNE Interventions mupirocin ointment 2%, 2 td, 10 to 11 days neomycin ointment 1%, 2 td, 10 to 11 days Outcomes time of evaluation NR cure/improved/failure Notes LTFU mupi 0/15, Neomycin 1/18 SE nil reported Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 45 Kiani 1991 Methods time NR multicentre USA (Southern States) admitted + outpatients Range (18/179) Participants Age > 16, . 211/154 (all participants) S. aureus 152/179, S. pyogones 29/179 (all patients) PE Interventions azithromycin 500 mg day 1, 250 mg, day 2 to 5, 5 days cephalexin 500 mg twice daily, 10 days Outcomes 11 days, cured/improved Notes 253 entered, 41 LTFU, 21 resistant pathogen, 12 excluded for other reasons 179 evaluable SE: no subgroup data Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Koning 2002 Methods 1999 Feb to 2000 Nov Rotterdam, Netherlands general practice only impetigo Participants < 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 Interventions fusidic acid cream 2%, 3 td + povidone-iodine shampoo, 2 td placebo cream, 3 td + povidone-iodine shampoo, 2 td Outcomes Seven days, cure Notes LTFU: 4/160 (2 in each group) SE: FA 7/76, P 19/80 (mainly pain and burning by povidone-iodine) Risk of bias Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 46 Koning 2002 (Continued) Item Authors’ judgement Description Allocation concealment? Yes A - Adequate Koranyi 1976 Methods 1974 Columbus, Ohio, USA outpatients only impetigo Participants 2 m to 15 yrs. M/F 14/16. S. aureus 22/30, S. pyogenes 10/30 PNE Interventions bacitracin ointment 500 units/g, 4 td + oral placebo 6 days erythromycin 250 mg 4 td + placebo cream, 6 days Outcomes Six days, cured/improved Notes LTFU: 0/60 SE: mild abdominal cramps E 2/15, B 0/15 Risk of bias Item Authors’ judgement Description Allocation concealment? Yes A - Adequate McLinn 1988 Methods 1986 Feb to May Scottsdale Arizona USA outpatients only impetigo Participants > 6 months, average 5.5 yrs. S.aureus 43/60, S.pyogenes 17/60 PE Interventions 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 Outcomes 8 to 12 days, very much improved/ improved/no change Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 47 McLinn 1988 (Continued) Notes LTFU: 0 SE: M: 0/30, E 6/30 (gastrointestinal) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Mertz 1989 Methods time NR San Juan Puerto Rico outpatients only impetigo Participants 6 m to 32 yrs, average 5.4 yrs M/F 27/26 S.aureus 44/53, GABHS 37/53 PE Interventions mupirocin ointment 2%, 3 td, 7 to 9 days erythromycin 30 to 50 mg/kg/day in 2 doses, 7 to 9 days Outcomes Seven to nine days, cured/improved Notes LTFU: 0 SE nil reported Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Montero 1996 Methods time NR Multicenter: Columbia Guatemala, Panama, S. Africa. outpatients Range (95/200) Participants 6 m to 12 yrs, M/F 101/94 (all participants) S.aureus 109/200, S.pyogenes 39/200 PNE Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 Outcomes 10 to 14 days, cured + improved Notes LTFU 2/100 in each group SE: A: 3 of 100 C: 2 of 100 (all mild skin side effects) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Moraes Barbosa 1986 Methods time NR Rio de Janeiro, Brasil Hospital outpatients only impetigo Participants 3 to 14 days, average 11 days. M/F 25/23 S.aureus 100% (inclusion criterion) Interventions 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 Outcomes Seven days, cure Notes SE: NR study on newborn Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 49 Morley 1988 Methods time NR Plymouth/Bristol/UK general practice Range (89/354) Participants 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 Interventions fusidic acid ointment 2%, 3 td, up to 7 days mupirocin ointment 2%, 3 td, up to 7 days Outcomes Six to eight days, excellent/good Notes SE: no subgroup data Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Nolting 1988 Methods time NR Münster, Germany outpatients Range (66/80) Participants 1 to 65 yrs, average 24 yrs. M/F 35/31 S.aureus 41/66, GABHS 8/66, both 17/66. PE Interventions sulconazole nitrate cream 1%, 2 td, 14 days miconazole nitrate cream 2%, 2 td, 14 days Outcomes 7 days/14 days, cure Notes SE mild burning S: 0/32 M: 1/34 Risk of bias Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 50 Nolting 1988 (Continued) Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Park 1993 Methods 1991 Aug to 1992 Sep Pusan / S-Korea outpatients only impetigo Participants Children, 88% 1 to 9 yrs M/F42/35. S. aureus 90% Interventions erythromycin 30 to 40 mg/kg/d fusidic acid cream 20 to 40 mg/kg/d, 3 to 5 days cefuroxim 250 mg/day Outcomes One week, excellent/good Notes LTFU 18 of 77 5 of 77 cases had bullous impetigo SE: NR Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Pruksachat. 1993 Methods 1988 Dec to 1990 Nov Chiang Mai, Thailand outpatients only impetigo Participants 1 m to 8 yrs. median 3.5 yrs, M/F 64/46 (all patients) S. aureus 77/110 PE Interventions penicillin V potassium 50 mg/kg/day in 4 doses, 7 days cloxacillin sodium 50 mg/kg/day in 4 doses, 7 days Outcomes Seven days, cure Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 51 Pruksachat. 1993 (Continued) Notes Bullous and non-bullous impetigo SE: NR Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Rice 1992 Methods 1989 Apr to Nov Baltimore USA outpatients and general practice. Only impetigo Participants 3 m to 16 yrs. MF 53/30 Culture done only in case of therapy failure. PNE Interventions erytromycin ethynyl succinate 40 mg/kg/day in 4 doses, 10 days mupirocin ointment 2%, 3 td, 10 days Outcomes 9 to 11 days,cure/improved/failure Notes 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 Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Rodriguez 1993 Methods time NR. Multicentre: Costa Rica, Guatemala, Panama, Venezuela. outpatients, Range (39/118) Participants 2 to 12 yrs, mean 5 yrs, M/F NR S. aureus 69/118, S. pyogenes 9/118 (all participants) PNE Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 flucloxacillin 500 to 2000 mg/day in 4 doses, see notes Outcomes Seven to ten days, cure/improved/failure Notes 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) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Rojas 1985 Methods time NR Dominican Republic hospital outpatients only impetigo Participants age, M/F ratio NR bacterial results NR PE Interventions mupirocin ointment 2%, 3 td, 10 to 12 days placebo/vehicle, 3 td, 10 to 12 days Outcomes 7 to 12 days,cure/improved Notes SE: mupirocin 0/52. vehicle 1/52 (nausea/vomiting) Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 53 Ruby 1973 Methods 1972 summer Dallas USA outpatients only impetigo Participants Children, M/F 43/59 only GABHS 33/102, both S. aureus and GABHS 57/102 PNE Interventions 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 Outcomes Five days, cure Notes SE: NR Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Sutton 1992 Methods time NR United Kingdom general practice (n = 20) only impetigo (only facial) Participants 1 m to 77 yrs, average 22 yrs. M/F 84/93 S. aureus 68/177 PNE Interventions fusidic acid cream 3 td, 6 to 8 days mupirocin ointment 3 td, 6 to 8 days Outcomes Eight days, cure + improved Notes skin SE: FA 2/104 M 4/97 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 54 Sutton 1992 (Continued) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Tack 1997 Methods 1992 July to 1993 Aug multicentre US outpatients. Range (225/394) Participants 0 to 13 yrs (median 5.4) M/F 217/197 S. aureus 284/394 (all participants) PE Interventions cefdinir 7 mg/kg/day , 2 td, 10 days cephalexin 10 mg/kg/day, 4 td, 10 days Outcomes 7 to 14 day, cure Notes SE: no subgroup data available Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Tack 1998 Methods 1992 Jan to Dec multicenter USA outpatients Range (62/952) Participants 13 to 88 yrs, M/F 564/388 (all participants), S. aureus 308/382 (all participants) PE Interventions cefdinir caps 300 mg, 2 td, 10 days cephalexin caps 500 mg, 4 td, 10 days Outcomes 7 to 16 days, cure/improved Notes SE: no subgroup data available included only participants that had pathogen susceptible to both study drugs Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 55 Tack 1998 (Continued) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Tamayo 1991 Methods time NR Mexico outpatients only impetigo Participants 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 Interventions rifamycin spray, 2 td, 7 days mupirocin ointment 2%, 2td, 7 days Outcomes One week, cure/improved Notes SE: nil reported Both primary (n = 17) and secondary (n = 13) impetigo participants Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Tassler 1993 Methods time NR. Multicentre (Europe and S. America) hospital admitted and outpatients Range (42/172) Participants Age 18 to 99 yrs, M/F 159/125 (all part) S. aureus 58% (all participants) PE Interventions fleroxacin 400 mg, 1 td, 7 to 21 days amoxicillin/clavulanic acid tablets 500/125 mg, 3 td, 7 to 21 days Outcomes Seven days, cure Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 56 Tassler 1993 (Continued) Notes SE: no subgroup data available Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Vainer 1986 Methods 1982 Mar to 1984 Jan Denmark general practice only impetigo Participants Age 1 to 77, average 11 yrs M/F 71/57 No bacterial culture done, PNE Interventions fusidic acid cream 2% Tetracycline/polymyxin B ointment neomycin/bacitracin ointment Outcomes One week, cure/improved Notes LTFU: 6 of 134 SE: total 3% FA; skin rash 1/43. T+P and N+B: burning and itching both one Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Wachs 1976 Methods 1974 multicenter USA outpatients only impetigo (secondary) Participants age/sex NR S. aureus 62/79 PNE Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 57 Wachs 1976 (Continued) Interventions bethametasone valerate cream, 3 td gentamycin cream, 3 td bethametasone + gentamycin cream, 3 td Outcomes Three weeks, excellent result Notes SE: NR Secondary impetigo (impetiginised atopic dermatitis) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Wainscott 1985 Methods time NR London, United Kingdom outpatients and general practice Range (16/39) Participants Age NR M/F 25/14 (all participants) S. aureus 31/48 (all participants) Part. excluded: not clear Interventions mupirocin ointment 2%, 2 td, 7 to 14 days chlortetracycline cream 3%, 2 td, 7 to 14 days Outcomes Seven days, cure/improved Notes SE: nil reported Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 58 Welsh 1987 Methods time NR Monterrey, Mexico outpatients Range (15/60) Participants Age NR, M/F32/28 S. aureus 47/50 PNE Interventions mupirocin ointment 2%, 3 td, 5 to 10 days ampicillin 50 mg, 4 td, 5 to 10 days Outcomes Ten days, cure/improved Notes LTFU 2/15 SE: nil reported Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear White 1989 Methods 1985 to 1987 United Kingdom general practice Range (155/390) Participants Age 11 m to 84 yrs, M/F NR S. aureus 43% (all participants) PNE Interventions mupirocin ointment 2%, 2 td, 7 days fusidic acid ointment 2%, 3 td, 7 days Outcomes Seven days, cure/improved Notes SE: minor itching or burning M: 6/263 FA: 2/127 (all participants) Risk of bias Item Authors’ judgement Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Description 59 White 1989 (Continued) Allocation concealment? Unclear B - Unclear Wilkinson 1988 Methods time NR Quebec, Canada outpatients Range (10/50) Participants Age/ sex NR S. aureus 18/50 (all participants) Part. excluded: not clear Interventions mupirocin 2%, 3 td, 7 days polymyxin B-neomycin (Neosporin), 3 td, 7 days Outcomes Seven days, cure/improved Notes SE: rash: M: 0/24 N: 1/26 (all participants) Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear 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 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 60 Characteristics of excluded studies [ordered by study ID] Alavena 1987 inadequate randomisation (excluded during quality score phase) Anonymous 1998 results not separately described for impetigo participants; no randomisation Arata 1983 inadequate randomisation (serial allocation) Arata 1994 results not separately described for impetigo participants Arosemena 1977 results not separately described for impetigo participants; only 6/343 patients had impetigo Azimi 1999 results not separately described for impetigo participants Baldwin 1981 same drug compared Ballantyne 1982 results not separately described for impetigo participants; no randomisation Bastin 1982 results not separately described for impetigo patients Bernard 1997 results not separately described for impetigo participants. requested, no reply Bin Jaafar 1987 no impetigo ( “pyoderma”) Burnett 1963 no randomisation (excluded in quality score phase) Cassels-Brown 1981 unacceptable design, no rct Colin 1988 results not separately described for impetigo participants Cordero 1976 only one impetigo participant Dillon 1970 no randomisation (excluded during quality phase) Dillon 1979 results not separately described for impetigo participants Drehobl 1997 results not separately described for impetigo participants. requested, no reply El Mofty 1990 results not separately described for impetigo participants Esterly 1970 no randomisation (excluded during quality score phase) Faingezicht 1992 results not separately described for impetigo participants Fedorovskaya 1989 inadequate randomisation Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 61 (Continued) Fleisher 1983 results not separately described for impetigo participants Forbes 1952 same drug compared Golcman 1997 results not separately described for impetigo participants. Requested, no reply Goldfarb 1987 results not separately described for impetigo participants Gooch 1991 results not separately described for impetigo participants Hanfling 1992 results not separately described for impetigo participants Harding 1970 one drug (flucloxacillin)in two doses; results for impetigo participants not separately described Heskel 1992 results not separately described for impetigo participants Jacobs 1992 results not separately described for impetigo participants Jennings 1999 one impetigo participant Keeny 1979 results not separately described for impetigo participants Kumakiri 1988 one impetigo participant Kumar 1988 no impetigo; two forms of same drug Lassus 1990 results not separately described for impetigo participants Lentino 1984 one impetigo participant Levenstein 1982 results not separately described for impetigo participants Lewis 1985 results not separately described for impetigo participants Linder 1993 results not separately described for impetigo participants Lipets 1987 no comparison made MacKenna 1945 inadequate randomisation./serial allocation, excluded during quality scoring phase. Macotela-Ruiz 1988 results not separately described for impetigo participants. requested, no reply. Mallory 1991 results not separately described for impetigo participants McCarty 1992 results not separately described for impetigo participants Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 62 (Continued) McMillan 1969 results not separately described for impetigo participants Milidiú d Silva 1985 results not separately described for impetigo participants Nakayama 1983 results not separately described for impetigo participants. no rct Neldner 1991 results not separately described for impetigo participants Nichols 1997 results not separately described for impetigo participants Nicolle 1990 results not separately described for impetigo participants Nolting 1992 no impetigo (pyoderma) Orecchio 1986 results not separately described for impetigo participants Palazzini 1993 results not separately described for impetigo participants Parish 1984 results not separately described for impetigo participants Parish 1991 results not separately described for impetigo participants Parish 1997 results not separately described for impetigo participants Pien 1983 results not separately described for impetigo participants Powers 1991 no separate results for clinical cure Powers 1993 only two impetigo participants Puspenogoro 1990 one impetigo participant Risser 1985 results not separately described for impetigo participants Saenz 1985 results not separately described for impetigo participants Salzberg 1972 one impetigo participant Schupbach 1992 results not separately described for impetigo participants Schwartz 1996 one impetigo participant Smith 1985 results not separately described for impetigo participants Smith 1993 one impetigo participant Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 63 (Continued) Sobye 1966 results not separately described for impetigo participants Stevens 1993 five participants with “pyoderma” Tack 1991 results not separately described for impetigo participants; same drug compared. Urbach 1966 no randomisation described. (exclude during quality score phase) Villiger 1986 results not separately described for impetigo participants Wachs 1992 results not separately described for impetigo participants Wolbling 1987 two doses of one drug compared Wong 1989 results not separately described for impetigo participants Yura 1988 results not separately described for impetigo participants Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 No. of participants 5 3 1 1 365 173 156 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 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 No. of participants Statistical method Effect size 807 440 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 1.56 [1.09, 2.24] 1.22 [0.69, 2.16] 17 Odds Ratio (M-H, Fixed, 95% CI) 13.91 [0.62, 312.60] 32 Odds Ratio (M-H, Fixed, 95% CI) 10.33 [0.51, 209.95] 16 Odds Ratio (M-H, Fixed, 95% CI) 12.0 [0.96, 150.69] 14 Odds Ratio (M-H, Fixed, 95% CI) 2.6 [0.09, 75.49] 8 Odds Ratio (M-H, Fixed, 95% CI) 1.36 [0.04, 46.65] 84 Odds Ratio (M-H, Fixed, 95% CI) 0.79 [0.33, 1.93] 87 Odds Ratio (M-H, Fixed, 95% CI) 1.16 [0.49, 2.73] 66 Odds Ratio (M-H, Fixed, 95% CI) 6.11 [0.67, 55.51] 43 Odds Ratio (M-H, Fixed, 95% CI) 3.31 [0.90, 12.13] Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 No. of participants 16 10 1021 581 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 1.60 [1.12, 2.29] 1.76 [1.05, 2.97] 3 197 Odds Ratio (M-H, Fixed, 95% CI) 3.73 [1.35, 10.34] 1 53 Odds Ratio (M-H, Fixed, 95% CI) 3.00 [0.12, 77.03] 1 17 Odds Ratio (M-H, Fixed, 95% CI) 0.67 [0.03, 12.84] 1 13 Odds Ratio (M-H, Fixed, 95% CI) 8.0 [0.46, 139.29] 1 37 Odds Ratio (M-H, Fixed, 95% CI) 8.38 [1.77, 39.69] 1 40 Odds Ratio (M-H, Fixed, 95% CI) 1.31 [0.37, 4.64] 1 30 Odds Ratio (M-H, Fixed, 95% CI) 0.25 [0.05, 1.14] 1 1 34 19 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 0.33 [0.03, 3.58] 0.06 [0.00, 0.67] Statistical method Effect size 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 No. of participants 2 1 292 36 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 1.84 [1.03, 3.29] 3.97 [0.15, 104.18] 1 256 Odds Ratio (M-H, Fixed, 95% CI) 1.79 [0.99, 3.23] Statistical method Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Effect size 66 Comparison 5. Non-bullous impetigo: oral antibiotics versus placebo Outcome or subgroup title 1 cure/improvement 1.1 penicillin No. of studies No. of participants 1 1 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 flucloxacillin 1.8 cefuroxim versus erythromycin No. of studies No. of participants 7 1 394 48 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 1.67 [0.93, 3.00] 15.67 [0.83, 295.88] 1 48 Odds Ratio (M-H, Fixed, 95% CI) 2.88 [0.11, 74.23] 1 18 Odds Ratio (M-H, Fixed, 95% CI) 3.0 [0.40, 22.71] 1 95 Odds Ratio (M-H, Fixed, 95% CI) 1.79 [0.29, 11.25] 1 34 Odds Ratio (M-H, Fixed, 95% CI) 0.54 [0.08, 3.74] 1 1 50 60 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 0.91 [0.17, 5.03] 0.25 [0.05, 1.30] 1 41 Odds Ratio (M-H, Fixed, 95% CI) 6.40 [1.44, 28.44] Statistical method Effect size 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 studies No. of participants 4 1 294 96 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 0.56 [0.24, 1.31] 0.87 [0.21, 3.71] 2 1 185 13 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 0.48 [0.14, 1.57] 0.29 [0.02, 3.52] Statistical method Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Effect size 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 flucloxacillin/dicloxacillin 1.5 clindamycin versus dicloxacillin No. of studies No. of participants 6 2 234 79 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 1.99 [0.92, 4.34] 8.82 [1.49, 52.01] 1 58 Odds Ratio (M-H, Fixed, 95% CI) 2.90 [0.11, 74.13] 1 16 Odds Ratio (M-H, Fixed, 95% CI) 2.33 [0.29, 18.96] 1 39 Odds Ratio (M-H, Fixed, 95% CI) 0.43 [0.08, 2.42] 1 42 Odds Ratio (M-H, Fixed, 95% CI) 1.10 [0.16, 7.39] Statistical method Effect size 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 No. of participants 1 1 66 66 Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 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 fleroxacin 1.3 cloxacillin versus penicillin No. of studies No. of participants 4 1 44 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Subtotals only 9.8 [1.09, 88.23] 1 42 Odds Ratio (M-H, Fixed, 95% CI) 1.68 [0.37, 7.63] 2 166 Odds Ratio (M-H, Fixed, 95% CI) 13.74 [4.36, 43.24] Statistical method Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Effect size 68 Comparison 11. Non-bullous impetigo: other comparisons of oral antibiotics Outcome or subgroup title 1 cure/improvement 1.1 lomefloxacin versus norfloxacin No. of studies No. of participants 1 1 18 18 Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 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 No. of participants 1 1 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 13. Non-bullous impetigo: disinfecting treatments versus placebo Outcome or subgroup title 1 cure/improvement 1.1 topical hexachlorophene No. of studies No. of participants 1 1 40 40 Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 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 studies No. of participants 1 1 24 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Subtotals only 55.0 [4.30, 703.43] 1 24 Odds Ratio (M-H, Fixed, 95% CI) 25.00 [2.92, 213.99] 1 24 Odds Ratio (M-H, Fixed, 95% CI) 2.2 [0.17, 28.14] Statistical method Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Effect size 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 No. of participants 1 1 120 24 Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 0.40 [0.18, 0.88] 3.57 [0.53, 23.95] 1 24 Odds Ratio (M-H, Fixed, 95% CI) 0.06 [0.01, 0.68] 1 24 Odds Ratio (M-H, Fixed, 95% CI) 0.14 [0.02, 0.96] 1 48 Odds Ratio (M-H, Fixed, 95% CI) 0.40 [0.11, 1.53] Statistical method Effect size 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 No. of participants 1 1 57 57 Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 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 No. of participants 1 1 54 54 Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 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 No. of participants 1 1 52 52 Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 No. of studies No. of participants 1 1 52 52 1 cure/improvement 1.1 betamethasone+gentamycin versus gentamycin Statistical method Effect size Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 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 No. of studies No. of participants 1 1 10 10 1 cure/improvement 1.1 cephalexin versus enoxacin Statistical method Effect size Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) 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 placebo Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio Eells 1986 14/17 8/19 10.7 % 6.42 [ 1.37, 30.05 ] Gould 1984 10/14 7/21 12.9 % 5.00 [ 1.15, 21.80 ] Rojas 1985 34/50 15/52 37.9 % 5.24 [ 2.25, 12.20 ] 81 92 61.6 % 5.40 [ 2.79, 10.45 ] 10/80 35.1 % 8.65 [ 3.88, 19.29 ] M-H,Fixed,95% CI 1 mupirocin Subtotal (95% CI) 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 0.01 0.1 favours placebo 1 10 100 favours topical ab (Continued . . . ) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 71 (. . . Study or subgroup placebo Odds Ratio n/N n/N M-H,Fixed,95% CI 76 80 35.1 % 8.65 [ 3.88, 19.29 ] 1/16 0/20 3.3 % 3.97 [ 0.15, 104.18 ] 16 20 3.3 % 3.97 [ 0.15, 104.18 ] 173 192 100.0 % 6.49 [ 3.93, 10.73 ] Subtotal (95% CI) Weight Continued) Odds Ratio topical antibiotic M-H,Fixed,95% CI Total events: 42 (topical antibiotic), 10 (placebo) Heterogeneity: not applicable Test for overall effect: Z = 5.27 (P < 0.00001) 3 bacitracin Ruby 1973 Subtotal (95% CI) Total events: 1 (topical antibiotic), 0 (placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.83 (P = 0.41) Total (95% CI) 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 1 favours placebo 10 100 favours topical ab Analysis 2.1. Comparison 2 Non-bullous impetigo: topical antibiotic versus another topical antibiotic, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 2 Non-bullous impetigo: topical antibiotic versus another topical antibiotic Outcome: 1 cure/improvement Study or subgroup antibiotic A antibiotic B Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio Gilbert 1989 4/8 6/11 5.3 % 0.83 [ 0.13, 5.17 ] Morley 1988 32/38 45/51 12.8 % 0.71 [ 0.21, 2.41 ] Sutton 1992 82/84 90/93 4.3 % 1.37 [ 0.22, 8.38 ] White 1989 81/106 33/49 22.4 % 1.57 [ 0.74, 3.31 ] 236 204 44.9 % 1.22 [ 0.69, 2.16 ] M-H,Fixed,95% CI 1 mupirocin versus fusidic acid Subtotal (95% CI) 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 favours antibiotic B 1 10 200 favours antibiotic A (Continued . . . ) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 72 (. . . Study or subgroup Weight Continued) Odds Ratio antibiotic A antibiotic B Odds Ratio n/N n/N M-H,Fixed,95% CI 8/8 5/9 0.6 % 13.91 [ 0.62, 312.60 ] 8 9 0.6 % 13.91 [ 0.62, 312.60 ] 15/15 13/17 0.8 % 10.33 [ 0.51, 209.95 ] 15 17 0.8 % 10.33 [ 0.51, 209.95 ] 6/7 3/9 0.8 % 12.00 [ 0.96, 150.69 ] 7 9 0.8 % 12.00 [ 0.96, 150.69 ] 6/6 7/8 1.0 % 2.60 [ 0.09, 75.49 ] 6 8 1.0 % 2.60 [ 0.09, 75.49 ] 2/2 5/6 1.2 % 1.36 [ 0.04, 46.65 ] 2 6 1.2 % 1.36 [ 0.04, 46.65 ] 26/43 27/41 23.0 % 0.79 [ 0.33, 1.93 ] 43 41 23.0 % 0.79 [ 0.33, 1.93 ] 26/43 25/44 20.6 % 1.16 [ 0.49, 2.73 ] 43 44 20.6 % 1.16 [ 0.49, 2.73 ] M-H,Fixed,95% CI 2 mupirocin versus rifamycin Tamayo 1991 Subtotal (95% CI) Total events: 8 (antibiotic A), 5 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 1.66 (P = 0.097) 3 mupirocin versus neomycin Kennedy 1985 Subtotal (95% CI) Total events: 15 (antibiotic A), 13 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 1.52 (P = 0.13) 4 mupirocin versus bacitracin Bass 1997 Subtotal (95% CI) Total events: 6 (antibiotic A), 3 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 1.92 (P = 0.054) 5 mupirocin versus chlortetracycline Wainscott 1985 Subtotal (95% CI) Total events: 6 (antibiotic A), 7 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 0.56 (P = 0.58) 6 mupirocin versus polymyxin B/neomycin Wilkinson 1988 Subtotal (95% CI) Total events: 2 (antibiotic A), 5 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 0.17 (P = 0.86) 7 fusidic acid versus neomycin/bacitracin Vainer 1986 Subtotal (95% CI) Total events: 26 (antibiotic A), 27 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 0.51 (P = 0.61) 8 fusidic acid versus tetracycline/polymyxin B Vainer 1986 Subtotal (95% CI) Total events: 26 (antibiotic A), 25 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 0.35 (P = 0.73) 0.005 0.1 favours antibiotic B 1 10 200 favours antibiotic A (Continued . . . ) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 73 (. . . Study or subgroup Weight Continued) Odds Ratio antibiotic A antibiotic B Odds Ratio n/N n/N M-H,Fixed,95% CI 5/32 1/34 1.7 % 6.11 [ 0.67, 55.51 ] 32 34 1.7 % 6.11 [ 0.67, 55.51 ] M-H,Fixed,95% CI 9 sulcanozol versus micanazol Nolting 1988 Subtotal (95% CI) Total events: 5 (antibiotic A), 1 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 1.61 (P = 0.11) 10 hydrocortisone+hydroxyquinoline versus hydrocortisone+miconazole Jaffe 1986 Subtotal (95% CI) 13/24 5/19 5.4 % 3.31 [ 0.90, 12.13 ] 24 19 5.4 % 3.31 [ 0.90, 12.13 ] 391 100.0 % 1.56 [ 1.09, 2.24 ] Total events: 13 (antibiotic A), 5 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 1.81 (P = 0.071) Total (95% CI) 416 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 favours antibiotic B 1 10 200 favours antibiotic A Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 74 Analysis 3.1. Comparison 3 Non-bullous impetigo: topical antibiotic versus oral antibiotic, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 3 Non-bullous impetigo: topical antibiotic versus oral antibiotic Outcome: 1 cure/improvement Study or subgroup topical antibiotic oral antibiotic Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio Barton 1989 47/49 43/48 3.7 % 2.73 [ 0.50, 14.83 ] Britton 1990 20/22 24/26 4.1 % 0.83 [ 0.11, 6.46 ] Dagan 1992 45/46 33/43 1.5 % 13.64 [ 1.66, 111.82 ] Dux 1986 17/24 8/12 6.4 % 1.21 [ 0.27, 5.38 ] Esterly 1991 21/22 18/20 1.8 % 2.33 [ 0.20, 27.91 ] Goldfarb 1988 29/29 27/29 0.9 % 5.36 [ 0.25, 116.76 ] 7/7 6/8 0.8 % 5.77 [ 0.23, 143.37 ] McLinn 1988 28/30 25/30 3.4 % 2.80 [ 0.50, 15.73 ] Mertz 1989 26/28 24/25 3.7 % 0.54 [ 0.05, 6.36 ] Rice 1992 30/41 34/42 18.6 % 0.64 [ 0.23, 1.81 ] 298 283 45.1 % 1.76 [ 1.05, 2.97 ] M-H,Fixed,95% CI 1 mupirocin versus erythromycin Gratton 1987 Subtotal (95% CI) 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 20/22 24/26 4.1 % 0.83 [ 0.11, 6.46 ] Dagan 1992 45/46 33/43 1.5 % 13.64 [ 1.66, 111.82 ] McLinn 1988 28/30 25/30 3.4 % 2.80 [ 0.50, 15.73 ] 98 99 9.1 % 3.73 [ 1.35, 10.34 ] 26/26 26/27 1.0 % 3.00 [ 0.12, 77.03 ] 26 27 1.0 % 3.00 [ 0.12, 77.03 ] Subtotal (95% CI) 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 Subtotal (95% CI) Total events: 26 (topical antibiotic), 26 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 0.66 (P = 0.51) 0.005 0.1 favours oral antibio 1 10 200 favours topical anti (Continued . . . ) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 75 (. . . Study or subgroup Weight Continued) Odds Ratio topical antibiotic oral antibiotic Odds Ratio n/N n/N M-H,Fixed,95% CI 6/7 9/10 2.2 % 0.67 [ 0.03, 12.84 ] 7 10 2.2 % 0.67 [ 0.03, 12.84 ] 8/9 2/4 0.6 % 8.00 [ 0.46, 139.29 ] 9 4 0.6 % 8.00 [ 0.46, 139.29 ] 11/18 3/19 2.3 % 8.38 [ 1.77, 39.69 ] 18 19 2.3 % 8.38 [ 1.77, 39.69 ] 11/18 12/22 8.7 % 1.31 [ 0.37, 4.64 ] 18 22 8.7 % 1.31 [ 0.37, 4.64 ] 5/15 10/15 13.8 % 0.25 [ 0.05, 1.14 ] 15 15 13.8 % 0.25 [ 0.05, 1.14 ] 1/16 3/18 5.5 % 0.33 [ 0.03, 3.58 ] 16 18 5.5 % 0.33 [ 0.03, 3.58 ] 3/9 9/10 11.7 % 0.06 [ 0.00, 0.67 ] 9 10 11.7 % 0.06 [ 0.00, 0.67 ] M-H,Fixed,95% CI 4 mupirocin versus cephalexin Bass 1997 Subtotal (95% CI) Total events: 6 (topical antibiotic), 9 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 0.27 (P = 0.79) 5 mupirocin versus ampicillin Welsh 1987 Subtotal (95% CI) Total events: 8 (topical antibiotic), 2 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 1.43 (P = 0.15) 6 fusidic acid versus erythromycin Park 1993 Subtotal (95% CI) Total events: 11 (topical antibiotic), 3 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 2.68 (P = 0.0074) 7 fusidic acid versus cefuroxim Park 1993 Subtotal (95% CI) Total events: 11 (topical antibiotic), 12 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 0.42 (P = 0.68) 8 bacitracin versus erythromycin Koranyi 1976 Subtotal (95% CI) Total events: 5 (topical antibiotic), 10 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 1.79 (P = 0.074) 9 bacitracin versus penicillin Ruby 1973 Subtotal (95% CI) Total events: 1 (topical antibiotic), 3 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 0.91 (P = 0.36) 10 bacitracin versus cephalexin Bass 1997 Subtotal (95% CI) Total events: 3 (topical antibiotic), 9 (oral antibiotic) Heterogeneity: not applicable 0.005 0.1 favours oral antibio 1 10 200 favours topical anti (Continued . . . ) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 76 (. . . Study or subgroup topical antibiotic oral antibiotic Odds Ratio n/N n/N M-H,Fixed,95% CI 514 507 Weight Continued) Odds Ratio M-H,Fixed,95% CI Test for overall effect: Z = 2.28 (P = 0.023) Total (95% CI) 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 1 favours oral antibio 10 200 favours topical anti Analysis 4.1. Comparison 4 Non-bullous impetigo: topical antibiotics versus disinfecting treatments, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 4 Non-bullous impetigo: topical antibiotics versus disinfecting treatments Outcome: 1 cure/improvement Study or subgroup topical antibiotic disinfectant Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio 1/16 0/20 2.4 % 3.97 [ 0.15, 104.18 ] 16 20 2.4 % 3.97 [ 0.15, 104.18 ] 105/128 92/128 97.6 % 1.79 [ 0.99, 3.23 ] 128 128 97.6 % 1.79 [ 0.99, 3.23 ] 148 100.0 % 1.84 [ 1.03, 3.29 ] M-H,Fixed,95% CI 1 bacitracin versus hexachlorophene Ruby 1973 Subtotal (95% CI) Total events: 1 (topical antibiotic), 0 (disinfectant) Heterogeneity: not applicable Test for overall effect: Z = 0.83 (P = 0.41) 2 fusidic acid versus hydrogen peroxide Christensen 1994 Subtotal (95% CI) Total events: 105 (topical antibiotic), 92 (disinfectant) Heterogeneity: not applicable Test for overall effect: Z = 1.92 (P = 0.055) Total (95% CI) 144 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 favours disinfectant 1 10 100 favours topical anti Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 77 Analysis 5.1. Comparison 5 Non-bullous impetigo: oral antibiotics versus placebo, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 5 Non-bullous impetigo: oral antibiotics versus placebo Outcome: 1 cure/improvement Study or subgroup oral antibiotic placebo n/N n/N Odds Ratio Weight 3/18 0/20 100.0 % 9.26 [ 0.44, 192.72 ] 18 20 100.0 % 9.26 [ 0.44, 192.72 ] M-H,Fixed,95% CI Odds Ratio M-H,Fixed,95% CI 1 penicillin Ruby 1973 Total (95% CI) Total events: 3 (oral antibiotic), 0 (placebo) Heterogeneity: not applicable Test for overall effect: Z = 1.44 (P = 0.15) 0.005 0.1 1 favours placebo 10 200 favours oral antibio Analysis 6.1. Comparison 6 Non-bullous impetigo: oral antibiotic (cephalosporin) versus another oral antibiotic, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 6 Non-bullous impetigo: oral antibiotic (cephalosporin) versus another oral antibiotic Outcome: 1 cure/improvement Study or subgroup cephalosporin other oral antibioti Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio 23/23 19/25 2.2 % 15.67 [ 0.83, 295.88 ] 23 25 2.2 % 15.67 [ 0.83, 295.88 ] 23/23 24/25 2.8 % 2.88 [ 0.11, 74.23 ] 23 25 2.8 % 2.88 [ 0.11, 74.23 ] M-H,Fixed,95% CI 1 cephalexin versus penicillin Demidovich 1990 Subtotal (95% CI) Total events: 23 (cephalosporin), 19 (other oral antibioti) Heterogeneity: not applicable Test for overall effect: Z = 1.84 (P = 0.066) 2 cephalexin versus erythromycin Demidovich 1990 Subtotal (95% CI) Total events: 23 (cephalosporin), 24 (other oral antibioti) Heterogeneity: not applicable 0.005 0.1 Favours other oral a 1 10 200 favours cephalospori (Continued . . . ) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 78 (. . . Study or subgroup Weight Continued) cephalosporin other oral antibioti Odds Ratio Odds Ratio n/N n/N M-H,Fixed,95% CI 6/8 5/10 6.4 % 3.00 [ 0.40, 22.71 ] 8 10 6.4 % 3.00 [ 0.40, 22.71 ] 49/51 41/44 9.9 % 1.79 [ 0.29, 11.25 ] 51 44 9.9 % 1.79 [ 0.29, 11.25 ] 13/16 16/18 16.2 % 0.54 [ 0.08, 3.74 ] 16 18 16.2 % 0.54 [ 0.08, 3.74 ] 21/24 23/26 15.8 % 0.91 [ 0.17, 5.03 ] 24 26 15.8 % 0.91 [ 0.17, 5.03 ] 25/33 25/27 38.2 % 0.25 [ 0.05, 1.30 ] 33 27 38.2 % 0.25 [ 0.05, 1.30 ] 12/22 3/19 8.4 % 6.40 [ 1.44, 28.44 ] 22 19 8.4 % 6.40 [ 1.44, 28.44 ] 194 100.0 % 1.67 [ 0.93, 3.00 ] M-H,Fixed,95% CI Test for overall effect: Z = 0.64 (P = 0.52) 3 cephalexin versus azithromycin Kiani 1991 Subtotal (95% CI) Total events: 6 (cephalosporin), 5 (other oral antibioti) Heterogeneity: not applicable Test for overall effect: Z = 1.06 (P = 0.29) 4 cefaclor versus azithromycin Montero 1996 Subtotal (95% CI) Total events: 49 (cephalosporin), 41 (other oral antibioti) Heterogeneity: not applicable Test for overall effect: Z = 0.62 (P = 0.53) 5 cefaclor versus amoxicillin/clavulanic acid Jaffe 1985 Subtotal (95% CI) Total events: 13 (cephalosporin), 16 (other oral antibioti) Heterogeneity: not applicable Test for overall effect: Z = 0.62 (P = 0.53) 6 cefadroxil versus penicillin Ginsburg 1978 Subtotal (95% CI) Total events: 21 (cephalosporin), 23 (other oral antibioti) Heterogeneity: not applicable Test for overall effect: Z = 0.10 (P = 0.92) 7 cefadroxil versus flucloxacillin Beitner 1996 Subtotal (95% CI) Total events: 25 (cephalosporin), 25 (other oral antibioti) Heterogeneity: not applicable Test for overall effect: Z = 1.65 (P = 0.099) 8 cefuroxim versus erythromycin Park 1993 Subtotal (95% CI) Total events: 12 (cephalosporin), 3 (other oral antibioti) Heterogeneity: not applicable Test for overall effect: Z = 2.44 (P = 0.015) Total (95% CI) 200 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 Favours other oral a 1 10 200 favours cephalospori Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 79 Analysis 7.1. Comparison 7 Non-bullous impetigo: oral cephalosporin versus other oral cephalosporin, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 7 Non-bullous impetigo: oral cephalosporin versus other oral cephalosporin Outcome: 1 cure/improvement Study or subgroup cephalosporin A cephalosporin B Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio 41/45 47/51 27.8 % 0.87 [ 0.21, 3.71 ] 45 51 27.8 % 0.87 [ 0.21, 3.71 ] M-H,Fixed,95% CI 1 cephalexin versus cefadroxil Hains 1989 Subtotal (95% CI) Total events: 41 (cephalosporin A), 47 (cephalosporin B) Heterogeneity: not applicable Test for overall effect: Z = 0.18 (P = 0.85) 2 cephalexin versus cefdinir Tack 1997 73/76 72/74 20.4 % 0.68 [ 0.11, 4.17 ] Tack 1998 11/17 15/18 36.5 % 0.37 [ 0.07, 1.80 ] 93 92 56.9 % 0.48 [ 0.14, 1.57 ] 2/4 7/9 15.3 % 0.29 [ 0.02, 3.52 ] 4 9 15.3 % 0.29 [ 0.02, 3.52 ] 152 100.0 % 0.56 [ 0.24, 1.31 ] Subtotal (95% CI) 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 Subtotal (95% CI) Total events: 2 (cephalosporin A), 7 (cephalosporin B) Heterogeneity: not applicable Test for overall effect: Z = 0.98 (P = 0.33) Total (95% CI) 142 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 1 favours cephalosp B Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 10 50 favours cephalosp A 80 Analysis 8.1. Comparison 8 Non-bullous impetigo: oral macrolide versus penicillin, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 8 Non-bullous impetigo: oral macrolide versus penicillin Outcome: 1 cure/improvement Study or subgroup oral macrolide penicillin n/N n/N Odds Ratio Weight Barton 1987 14/14 11/15 4.1 % 11.35 [ 0.55, 233.12 ] Demidovich 1990 24/25 19/25 8.4 % 7.58 [ 0.84, 68.46 ] 39 40 12.5 % 8.82 [ 1.49, 52.01 ] 28/28 29/30 5.4 % 2.90 [ 0.11, 74.13 ] 28 30 5.4 % 2.90 [ 0.11, 74.13 ] 7/10 3/6 12.4 % 2.33 [ 0.29, 18.96 ] 10 6 12.4 % 2.33 [ 0.29, 18.96 ] 18/25 12/14 47.6 % 0.43 [ 0.08, 2.42 ] 25 14 47.6 % 0.43 [ 0.08, 2.42 ] 23/26 14/16 22.1 % 1.10 [ 0.16, 7.39 ] 26 16 22.1 % 1.10 [ 0.16, 7.39 ] 106 100.0 % 1.99 [ 0.92, 4.34 ] M-H,Fixed,95% CI Odds Ratio M-H,Fixed,95% CI 1 erythromycin versus penicillin V Subtotal (95% CI) 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 Subtotal (95% CI) Total events: 28 (oral macrolide), 29 (penicillin) Heterogeneity: not applicable Test for overall effect: Z = 0.64 (P = 0.52) 3 azithromycin versus cloxacillin Daniel 1991b Subtotal (95% CI) Total events: 7 (oral macrolide), 3 (penicillin) Heterogeneity: not applicable Test for overall effect: Z = 0.79 (P = 0.43) 4 azithromycin versus flucloxacillin/dicloxacillin Rodriguez 1993 Subtotal (95% CI) Total events: 18 (oral macrolide), 12 (penicillin) Heterogeneity: not applicable Test for overall effect: Z = 0.96 (P = 0.34) 5 clindamycin versus dicloxacillin Blaszcyk 1998 Subtotal (95% CI) Total events: 23 (oral macrolide), 14 (penicillin) Heterogeneity: not applicable Test for overall effect: Z = 0.09 (P = 0.93) Total (95% CI) 128 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 favours penicillin 1 10 200 favours macrolide Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 81 Analysis 9.1. Comparison 9 Non-bullous impetigo: oral macrolide versus another oral macrolide, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 9 Non-bullous impetigo: oral macrolide versus another oral macrolide Outcome: 1 cure/improvement Study or subgroup oral macrolide A oral macrolide B Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio 28/35 21/31 100.0 % 1.90 [ 0.62, 5.83 ] 35 31 100.0 % 1.90 [ 0.62, 5.83 ] M-H,Fixed,95% CI 1 azithromycin versus erythromycin Daniel 1991a Total (95% CI) Total events: 28 (oral macrolide A), 21 (oral macrolide B) Heterogeneity: not applicable Test for overall effect: Z = 1.13 (P = 0.26) 0.2 0.5 1 favours macrolide B Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 2 5 favours macrolide A 82 Analysis 10.1. Comparison 10 Non-bullous impetigo: oral penicillin versus other oral antibiotic (including penicillin), Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 10 Non-bullous impetigo: oral penicillin versus other oral antibiotic (including penicillin) Outcome: 1 cure/improvement Study or subgroup penicillin A antibiotic B Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio M-H,Fixed,95% CI 1 amoxicillin+clavulanic acid versus amoxicillin Dagan 1989 Subtotal (95% CI) 21/22 15/22 100.0 % 9.80 [ 1.09, 88.23 ] 22 22 100.0 % 9.80 [ 1.09, 88.23 ] 12/15 19/27 100.0 % 1.68 [ 0.37, 7.63 ] 15 27 100.0 % 1.68 [ 0.37, 7.63 ] Total events: 21 (penicillin A), 15 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 2.04 (P = 0.042) 2 amoxicillin+clavulanic acid versus fleroxacin Tassler 1993 Subtotal (95% CI) Total events: 12 (penicillin A), 19 (antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 0.68 (P = 0.50) 3 cloxacillin versus penicillin Gonzalez 1989 33/33 23/43 13.1 % 58.45 [ 3.37, 1015.02 ] Pruksachat. 1993 42/45 30/45 86.9 % 7.00 [ 1.86, 26.34 ] 78 88 100.0 % 13.74 [ 4.36, 43.24 ] Subtotal (95% CI) 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 1 10 100 1000 favours penicillin A Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 83 Analysis 11.1. Comparison 11 Non-bullous impetigo: other comparisons of oral antibiotics, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 11 Non-bullous impetigo: other comparisons of oral antibiotics Outcome: 1 cure/improvement Study or subgroup lomefloxacin norfloxacin n/N n/N Odds Ratio Weight 6/10 3/8 100.0 % 2.50 [ 0.37, 16.89 ] 10 8 100.0 % 2.50 [ 0.37, 16.89 ] M-H,Fixed,95% CI Odds Ratio M-H,Fixed,95% CI 1 lomefloxacin versus norfloxacin Arata 1989b Total (95% CI) Total events: 6 (lomefloxacin), 3 (norfloxacin) Heterogeneity: not applicable Test for overall effect: Z = 0.94 (P = 0.35) 0.05 0.2 1 favours norfloxacin 5 20 favours lomefloxacin Analysis 12.1. Comparison 12 Non-bullous impetigo: oral antibiotics versus disinfecting treatments, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 12 Non-bullous impetigo: oral antibiotics versus disinfecting treatments Outcome: 1 cure/improvement Study or subgroup oral antibiotic disinfectant Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio 3/18 0/20 100.0 % 9.26 [ 0.44, 192.72 ] 18 20 100.0 % 9.26 [ 0.44, 192.72 ] M-H,Fixed,95% CI 1 penicillin versus hexachlorophene Ruby 1973 Total (95% CI) Total events: 3 (oral antibiotic), 0 (disinfectant) Heterogeneity: not applicable Test for overall effect: Z = 1.44 (P = 0.15) 0.005 0.1 favours disinfectant 1 10 200 favours oral antibio Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 84 Analysis 13.1. Comparison 13 Non-bullous impetigo: disinfecting treatments versus placebo, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 13 Non-bullous impetigo: disinfecting treatments versus placebo Outcome: 1 cure/improvement Study or subgroup disinfectant placebo Odds Ratio Odds Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI 0/20 0/20 0.0 [ 0.0, 0.0 ] 20 20 0.0 [ 0.0, 0.0 ] 1 topical hexachlorophene Ruby 1973 Total (95% CI) Total events: 0 (disinfectant), 0 (placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P < 0.00001) 0.1 0.2 0.5 favours placebo 1 2 5 10 favours disinfectant Analysis 14.1. Comparison 14 Bullous impetigo: topical antibiotic versus another topical antibiotic, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 14 Bullous impetigo: topical antibiotic versus another topical antibiotic Outcome: 1 cure/improvement Study or subgroup topical antibiotic A topical antibiotic B Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio Moraes Barbosa 1986 10/12 1/12 100.0 % 55.00 [ 4.30, 703.43 ] Subtotal (95% CI) 12 12 100.0 % 55.00 [ 4.30, 703.43 ] M-H,Fixed,95% CI 1 fusidic acid versus neomycin/bacitracin Total events: 10 (topical antibiotic A), 1 (topical antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 3.08 (P = 0.0021) 2 fusidic acid versus chloramphenicol Moraes Barbosa 1986 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 ] Total events: 10 (topical antibiotic A), 2 (topical antibiotic B) Heterogeneity: not applicable 0.001 0.01 0.1 favours antibiotic B 1 10 100 1000 favours antibiotic A (Continued . . . ) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 85 (. . . Study or subgroup Weight Continued) Odds Ratio topical antibiotic A topical antibiotic B Odds Ratio n/N n/N M-H,Fixed,95% CI Moraes Barbosa 1986 2/12 1/12 100.0 % 2.20 [ 0.17, 28.14 ] Subtotal (95% CI) 12 12 100.0 % 2.20 [ 0.17, 28.14 ] M-H,Fixed,95% CI Test for overall effect: Z = 2.94 (P = 0.0033) 3 chloramphenicol versus neomycin/bacitracin Total events: 2 (topical antibiotic A), 1 (topical antibiotic B) Heterogeneity: not applicable Test for overall effect: Z = 0.61 (P = 0.54) 0.001 0.01 0.1 1 favours antibiotic B 10 100 1000 favours antibiotic A Analysis 15.1. Comparison 15 Bullous impetigo: topical antibiotic versus oral antibiotic, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 15 Bullous impetigo: topical antibiotic versus oral antibiotic Outcome: 1 cure/improvement Study or subgroup topical antibiotic oral antibiotic Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio Moraes Barbosa 1986 10/12 7/12 5.8 % 3.57 [ 0.53, 23.95 ] Subtotal (95% CI) 12 12 5.8 % 3.57 [ 0.53, 23.95 ] M-H,Fixed,95% CI 1 fusidic acid versus erythromycin Total events: 10 (topical antibiotic), 7 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 1.31 (P = 0.19) 2 neomycin/bacitracin versus erythromycin Moraes Barbosa 1986 1/12 7/12 31.9 % 0.06 [ 0.01, 0.68 ] Subtotal (95% CI) 12 12 31.9 % 0.06 [ 0.01, 0.68 ] Total events: 1 (topical antibiotic), 7 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 2.28 (P = 0.022) 3 chloramphenicol versus erythromycin Moraes Barbosa 1986 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 ] Total events: 2 (topical antibiotic), 7 (oral antibiotic) Heterogeneity: not applicable 0.01 0.1 1 favours oral antibio 10 100 favours topical anti (Continued . . . ) Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 86 (. . . Study or subgroup topical antibiotic oral antibiotic Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Continued) Odds Ratio M-H,Fixed,95% CI 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 % 0.40 [ 0.11, 1.53 ] Subtotal (95% CI) 36 12 33.3 % 0.40 [ 0.11, 1.53 ] 48 100.0 % 0.40 [ 0.18, 0.88 ] Total events: 13 (topical antibiotic), 7 (oral antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 1.33 (P = 0.18) Total (95% CI) 72 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 1 10 favours oral antibio 100 favours topical anti Analysis 16.1. Comparison 16 Bullous impetigo; oral antibiotic versus another oral antibiotic, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 16 Bullous impetigo; oral antibiotic versus another oral antibiotic Outcome: 1 cure/improvement Study or subgroup cephalexin dicloxacillin n/N n/N Odds Ratio Weight 26/28 23/29 100.0 % 3.39 [ 0.62, 18.49 ] 28 29 100.0 % 3.39 [ 0.62, 18.49 ] M-H,Fixed,95% CI Odds Ratio M-H,Fixed,95% CI 1 cephalexin versus dicloxacillin Dillon 1983 Total (95% CI) Total events: 26 (cephalexin), 23 (dicloxacillin) Heterogeneity: not applicable Test for overall effect: Z = 1.41 (P = 0.16) 0.05 0.2 favours dicloxacilli 1 5 20 favours cephalexin Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 87 Analysis 17.1. Comparison 17 Secondary impetigo: steroid versus antibiotic, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 17 Secondary impetigo: steroid versus antibiotic Outcome: 1 cure/improvement Study or subgroup steroid antibiotic Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio M-H,Fixed,95% CI 1 betamethasone versus gentamycin Wachs 1976 Total (95% CI) 15/27 8/27 100.0 % 2.97 [ 0.97, 9.12 ] 27 27 100.0 % 2.97 [ 0.97, 9.12 ] Total events: 15 (steroid), 8 (antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 1.90 (P = 0.057) 0.1 0.2 0.5 1 favours antibiotic 2 5 10 favours steroid Analysis 18.1. Comparison 18 Secondary impetigo: steroid+antibiotic versus steroid, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 18 Secondary impetigo: steroid+antibiotic versus steroid Outcome: 1 cure/improvement Study or subgroup steroid+antibiotic steroid n/N n/N Odds Ratio Weight M-H,Fixed,95% CI Odds Ratio M-H,Fixed,95% CI 1 betamethasone+gentamycin versus betamethasone Wachs 1976 Total (95% CI) 18/25 15/27 100.0 % 2.06 [ 0.65, 6.54 ] 25 27 100.0 % 2.06 [ 0.65, 6.54 ] Total events: 18 (steroid+antibiotic), 15 (steroid) Heterogeneity: not applicable Test for overall effect: Z = 1.22 (P = 0.22) 0.1 0.2 0.5 favours steroid 1 2 5 10 favours steroid+ab Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 88 Analysis 19.1. Comparison 19 Secondary impetigo: steroid+antibiotic versus antibiotic, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 19 Secondary impetigo: steroid+antibiotic versus antibiotic Outcome: 1 cure/improvement Study or subgroup steroid+antibiotic antibiotic Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio M-H,Fixed,95% CI 1 betamethasone+gentamycin versus gentamycin Wachs 1976 18/25 8/27 100.0 % 6.11 [ 1.84, 20.31 ] 25 27 100.0 % 6.11 [ 1.84, 20.31 ] Total (95% CI) Total events: 18 (steroid+antibiotic), 8 (antibiotic) Heterogeneity: not applicable Test for overall effect: Z = 2.95 (P = 0.0032) 0.05 0.2 1 favours antibiotic 5 20 favours steroid+ab Analysis 20.1. Comparison 20 Secondary impetigo: oral antibiotic versus another oral antibiotic, Outcome 1 cure/improvement. Review: Interventions for impetigo Comparison: 20 Secondary impetigo: oral antibiotic versus another oral antibiotic Outcome: 1 cure/improvement Study or subgroup cephalexin enoxacin Odds Ratio n/N n/N M-H,Fixed,95% CI Weight Odds Ratio 2/4 4/6 100.0 % 0.50 [ 0.04, 6.68 ] 4 6 100.0 % 0.50 [ 0.04, 6.68 ] M-H,Fixed,95% CI 1 cephalexin versus enoxacin Fujita 1984 Total (95% CI) Total events: 2 (cephalexin), 4 (enoxacin) Heterogeneity: not applicable Test for overall effect: Z = 0.52 (P = 0.60) 0.05 0.2 favours enoxacin 1 5 20 favours cephalexin Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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$).ti,ab. 24. OR/18-23 25. LIMIT 24 TO HUMAN 26. STAPHYLOCOCCAL SKIN INFECTIONS/ 27. IMPETIGO/ 28. IMPETIGO.ti,ab. 29. PYODERMA.ti,ab. 30. OR/26-29 31. 30 and 25 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 90 Appendix 4. EMBASE (from 1980 to March 2000) search strategy 1. exp clinical trial/ or exp randomized controlled trial/ 2. (clinical trial or randomized controlled trial).af. 3. exp controlled study/ or controlled clinical trial.mp. 4. random$.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 WHAT’S NEW Last assessed as up-to-date: 26 November 2002. 4 October 2008 Amended Converted to new review format. Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 91 HISTORY Protocol first published: Issue 4, 2001 Review first published: Issue 2, 2004 2 September 2004 New search has been performed Minor update 4 January 2003 Amended New studies found but not yet included or excluded 27 November 2002 New citation required and conclusions have changed Substantive amendment Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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)). Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 Interventions for impetigo (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 94
