1. No category

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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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INDEX TERMS
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[Intervention Review]
Interventions for impetigo
Sander Koning1 , Arianne P Verhagen1 , Lisette WA van Suijlekom-Smit2 , Andrew D Morris3 , Christopher Butler4 , Johannes C van
der Wouden5
1 Department
of General Practice, Erasmus MC, University Medical Center, Rotterdam, Netherlands. 2 Department of Pediatrics,
Erasmus MC, University Medical Center, Rotterdam, Netherlands. 3 Department of Dermatology, University of Wales College of
Medicine, Cardiff, UK. 4 Department of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK.
5
Department of General Practice, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands
Contact address: Sander Koning, Department of General Practice, Erasmus MC, University Medical Center, Room Ff337, PO Box
1738, Rotterdam, 3000 DR, Netherlands. [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)
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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
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2000). Pyoderma is sometimes used as a synonym for impetigo in
tropical countries, usually to denote streptococcal as opposed to
staphylococcal impetigo.
Bullous impetigo is characterised by larger bullae or blisters that
rupture less readily and can persist for several days. Usually there
are fewer lesions and the trunk is affected more frequently than
in non-bullous impetigo. Diagnostic confusion can occur with
thermal burns, blistering disorders (e.g. bullous pemphigoid) and
Stevens Johnson syndrome.
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.
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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).
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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.
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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.
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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?
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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
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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
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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
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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
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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
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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
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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).
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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).
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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).
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(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
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Arredondo 1987 {published data only}
Arredondo JL. Efficacy and tolerance of topical mupirocin
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Barton 1987 {published data only}
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therapy. Pediatric Dermatology 1987;4:185–8.
Barton 1988 {published data only}
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comparison of erythromycin and dicloxacillin therapy. Pediatric
Dermatology 1988;5:88–91.
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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
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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}
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Britton 1990 {published data only}
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Dagan 1989 {published data only}
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acid (Augmentin) for the treatment of nonbullous impetigo.
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Dagan 1992 {published data only}
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Daniel 1991a {published data only}
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Dillon 1983 {published data only}
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Dux 1986 {published data only}
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Eells 1986 {published data only}
Eells LD, Mertz PM, Piovanetti Y, Pekoe GM, Eaglstein WH.
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Esterly 1991 {published data only}
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Gilbert 1989 {published data only}
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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
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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:
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Gould 1984 {published data only}
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Gratton 1987 {published data only}
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Daniel 1991b {published data only}
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Hains 1989 {published data only}
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Jaffe 1986 {published data only}
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Kennedy 1985 {published data only}
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Kiani 1991 {published data only}
Kiani R. Double-blind, double-dummy comparison of
azithromycin and cephalexin in the treatment of skin and skin
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Koning 2002 {published data only}
∗
Koning S, van Suijlekom-Smit LWA, Nouwen JL, Verduin CM,
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Koranyi 1976 {published data only}
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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
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(4):1069–73.
∗
Mertz PM, Marshall DA, Eaglstein WH, Piovanetti Y, Montalvo
J. Topical mupirocin treatment of impetigo is equal to oral
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Montero 1996 {published data only}
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tolerability of azithromycin and cefaclor in the treatment of
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Moraes Barbosa 1986 {published data only}
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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%,
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Morley 1988 {published data only}
Morley PAR, Munot LD. A comparison of sodium fusidate
ointment and mupirocin ointment in superficial skin sepsis.
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Nolting 1988 {published data only}
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Park 1993 {published data only}
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causative organism, antimicrobial susceptibility tests and
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Pruksachat. 1993 {published data only}
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Rice 1992 {published data only}
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∗
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Interventions for impetigo (Review)
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22
cephalexin for the treatment of skin and skin-structure infections.
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∗
Wachs GN, Maibach HI. Co-operative double-blind trial of an
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References to studies excluded from this review
Alavena 1987 {published data only}
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Anonymous 1998 {published data only}
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Arosemena 1977 {published data only}
∗
Arosemena R, Bogaert H, Bonilla Dib E, Close de León J,
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Bastin 1982 {published data only}
Bastin R, Rapin M, Kernbaum S. Controlled study of
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Bernard 1997 {published data only (unpublished sought but not used)}
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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
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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
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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
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Dagan R, Barr-David Y. Double blind study comparing
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treatments. Pediatric annals 1993;22:235–40.
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staphylococci in the Netherlands: Surveillance by an electronic
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1998;41:93–101.
Dillon 1979
Dillon HC. Post-streptococcal glomerulonephritis following
pyoderma. Review of Infectious Diseases 1979;1:935–43.
Espersen 1998
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practice. British Journal of Dermatology 1998;139:4–8.
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Kristensen 1991
Kristensen JK. Scabies and pyoderma in Lilongwe, Malawi:
Prevalence and seasonal fluctuation. International Journal of
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MacKenna
MacKenna RMD, Cooper-Willis ES. Impetigo in the army, treated
with microcrystalline sulphathiazole. Lancet 1945;269:357–8.
McCormick 1995
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Ruby 1973
Ruby RJ, Nelson JD. The influence of hexachlorophene scrubs on
the response to placebo or penicillin therapy in impetigo. Pediatrics
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Smeenk 1999
Smeenk G, Sebens FW, Houwing RH. Use and disadvantages of
local antibiotics and disinfectants on the skin [Nut en gevaren van
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∗
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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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
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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)
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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
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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
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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 . . . )
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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)
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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
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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)
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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
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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$).ti,ab.
24. OR/18-23
25. LIMIT 24 TO HUMAN
26. STAPHYLOCOCCAL SKIN INFECTIONS/
27. IMPETIGO/
28. IMPETIGO.ti,ab.
29. PYODERMA.ti,ab.
30. OR/26-29
31. 30 and 25
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Appendix 4. EMBASE (from 1980 to March 2000) search strategy
1. exp clinical trial/ or exp randomized controlled trial/
2. (clinical trial or randomized controlled trial).af.
3. exp controlled study/ or controlled clinical trial.mp.
4. random$.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.
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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.
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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.
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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.
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