Impetigo
Impetigo - Summary
Impetigo is a common contagious infection of the superficial layers of the skin, usually caused by Staphylococcus aureus, and less commonly caused by Streptococcus pyogenes.
Impetigo predominantly affects children. The annual incidence is around 2.8% in children up to 4 years of age, and 1.6% in children 5–15 years of age.
Non-bullous impetigo (also known as impetigo contagiosa or crusted impetigo) is the most common form.
It presents as vesicles or pustules, which rapidly burst and evolve into gold-crusted plaques, typically 2 cm in diameter.
The area around the mouth and nose is most commonly affected, although other areas of the face and the extremities may also be involved.
Non-bullous impetigo is usually asymptomatic, although there may be some itching. Systemic symptoms are uncommon unless the infection is widespread.
Bullous impetigo commonly affects neonates, although older children and adults can also be affected.
It presents with flaccid, fluid-filled vesicles and blisters (bullae), that are usually at least 1–2 cm in diameter. These easily burst leaving raw skin, and eventually form thin, flat, brown-to-golden crusts.
The face is less commonly affected than with non-bullous impetigo; instead bullous impetigo tends to involve the axillae, neck folds, and nappy area. Lesions are often multiple and spread rapidly.
Lesions tend to be painful and systemic symptoms (weakness, fever, and diarrhoea) are more common; there may be regional lymphadenopathy.
Skin swabs are not usually necessary to diagnose impetigo, but may be taken (for bacterial identification and sensitivity) if the infection is:
Very extensive or severe.
Recurrent (consider nasal swab for staphylococcal carriage).
Suspected as being a community outbreak.
Suspected as being caused by meticillin-resistant Staphylococcus aureus (MRSA).
Other skin infections and infestations that should be excluded include cellulitis, erysipelas, ecthyma, candidiasis, dermatophytosis, herpes simples virus, varicella, and scabies.
Non-infective skin diseases that should be excluded include atopic eczema, contact dermatitis, insect bites, burns and scalds, drug reactions, Stevens–Johnson syndrome, and toxic epidermal necrolysis.
Hygiene measures are important to aid healing and stop the infection spreading to other sites on the body and to other people.
Children and adults should stay away from school or work until the lesions are dry and scabbed over or, if the lesions are still crusted or weeping, for 48 hours after antibiotic treatment has started.
Localized non-bullous infection should be treated with topical fusidic acid; topical mupirocin, retapamulin, and antiseptics are not recommended initially. More extensive or severe infection may require oral antibiotics (flucloxacillin or clarithromycin/erythromycin if allergic to penicillin).
Bullous infection usually requires treatment with an oral antibiotic (flucloxacillin or clarithromycin/erythromycin).
For people with recurrent impetigo, nasal swabs may be necessary to detect staphylococcal carriage. The immediate family may also need to be swabbed.
If Staphylococcus aureus is detected, hygiene measures should be adhered to, and nasal carriage eliminated with topical mupirocin.
Have I got the right topic?
This CKS topic covers the management of impetigo.
This CKS topic does not cover the management of infected wounds and burns, infected eczema, or cellulitis.
There are separate CKS topics on Boils, carbuncles, and staphylococcal carriage, Candida - skin, Cellulitis - acute, Dermatitis - contact, Eczema - atopic, Fungal skin infection - body and groin, and Fungal skin infection - scalp.
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.
CKS gratefully acknowledges the contribution of the British Association of Dermatologists in the development of this topic.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic [NICE, 2013].
October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic [NPC, 2012].
May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic [NPC, 2011]. Issued in June 2011.
August 2010 — minor update. The Health Protection Agency (HPA) advise that children (and adults) should stay away from school (or work) until the lesions have scabbed over, or for 48 hours after starting antibiotic treatment [HPA, 2010]. Issued in August 2010.
December 2008 to June 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.
Retapamulin has been included as a second-line treatment for localized areas of impetigo.
Previous changes
November 2008 — minor update. Clarithromycin added as an antibiotic option if a person is penicillin allergic. Issued in December 2008.
September 2008 — minor correction to the Changes section. Issued in September 2008.
October to December 2005 — reviewed. Validated in March 2006 and issued in May 2006.
September 2002 — written. Validated in October 2002 and issued in December 2002.
Update
New evidence
Evidence-based guidelines
No new evidence-based guidelines since 1 December 2008.
HTAs (Health Technology Assessments)
No new HTAs since 1 December 2008.
Economic appraisals
No new economic appraisals relevant to England since 1 December 2008.
Systematic reviews and meta-analyses
No new systematic review or meta-analysis since 1 December 2008.
Primary evidence
No new randomized controlled trials published in the major journals since 1 December 2008.
New policies
No new national policies or guidelines since 1 December 2008.
New safety alerts
No new safety alerts since 1 December 2008.
Changes in product availability
No changes in product availability since 1 December 2008.
Goals and outcome measures
Goals
Diagnose non-bullous and bullous impetigo
Provide advice about managing symptoms and preventing transmission of impetigo
Treat all people with topical or oral antibiotics
Assess causes of recurrent impetigo, including staphylococcal carriage in the person and immediate family
Refer chronic, recurrent, or severe impetigo that is not adequately managed in primary care
QIPP — Options for local implementation
QIPP — Options for local implementation
Antibiotic prescribing — especially quinolones and cephalosporins
Review and, where appropriate, revise current prescribing practice and use implementation techniques to ensure prescribing is in line with Health Protection Agency (HPA) guidance.
Review the total volume of antibiotic prescribing against local and national data.
Review the use of quinolones and cephalosporin prescribing against local and national data.
Background information
Definition
What is it?
Impetigo is a common contagious infection of the superficial layers of the skin.
Impetigo is classified as non-bullous (common) or bullous (uncommon). Non-bullous impetigo may also be further categorized as primary, or as secondary to an underlying cause (such as atopic eczema).
[Sladden and Johnston, 2004; Cole and Gazewood, 2007; DTB, 2007]
Causes
What causes it?
Impetigo is usually caused by Staphylococcus aureus, and less commonly caused by Streptococcus pyogenes [Sladden and Johnston, 2004; Cole and Gazewood, 2007; DTB, 2007].
Incidence
How common is it?
Impetigo predominantly affects children, with an annual incidence of around 2.8% in children up to 4 years of age, and 1.6% in children 5–15 years of age [Cole and Gazewood, 2007; DTB, 2007].
Complications
What are the complications?
Although impetigo is usually a self-limiting illness, it can cause psychological distress, and very rarely there may be complications associated with disseminated impetigo, such as immunologically-mediated glomerulonephritis, septicaemia, cellulitis, guttate psoriasis, or staphylococcal scalded skin syndrome [Cole and Gazewood, 2007; DTB, 2007].
Diagnosis
Diagnosis of impetigo
Diagnosis
How should I diagnose impetigo?
Diagnosis is made by identifying clinical features and ruling out conditions that mimic impetigo. Images of impetigo and its differential diagnoses can be found at www.dermnetnz.org.
Non-bullous impetigo (also known as impetigo contagiosa or crusted impetigo) is the most common form.
Lesions begin as vesicles or pustules, but these are rarely visible as they rapidly burst and evolve into gold-crusted plaques, typically 2 cm in diameter (these have been described as resembling glued-on cornflakes).
The area around the mouth and nose is most commonly affected, although other areas of the face and the extremities may also be involved. Satellite lesions may occur due to autoinoculation.
Non-bullous impetigo is usually asymptomatic, although there may be some itching. Systemic symptoms (such as fever) are uncommon unless the infection is widespread.
Bullous impetigo commonly affects neonates, although older children and adults can also be affected.
Bullous impetigo presents with flaccid, fluid-filled vesicles and blisters (bullae), that are usually at least 1–2 cm in diameter. These easily burst leaving raw skin, and eventually form thin, flat, brown-to-golden crusts.
The face is less commonly affected than with non-bullous impetigo; instead bullous impetigo tends to involve the axillae, neck folds, and nappy area. Lesions are often multiple and spread rapidly.
Unlike non-bullous impetigo, lesions tend to be painful. Systemic symptoms (weakness, fever, and diarrhoea) are more common, and there may be regional lymphadenopathy.
Skin swabs are not necessary to diagnose impetigo. Take a swab (for bacterial identification and sensitivity) if the infection is:
Very extensive or severe.
Recurrent (consider nasal swab for staphylococcal carriage).
Suspected as being a community outbreak.
Suspected as being caused by meticillin-resistant Staphylococcus aureus (MRSA), for instance if the person has been in contact with a person who has been diagnosed with MRSA.
Basis for recommendation
Basis for recommendation
Recommendations for the diagnosis and assessment of impetigo are based on expert opinion from narrative reviews [Sladden and Johnston, 2004; Watkins, 2005; Cole and Gazewood, 2007].
Differential diagnosis
What else might it be?
Skin infections and infestations
Cellulitis is bacterial infection of the dermis and epidermis. It presents with an acute onset of red, painful, hot, swollen, tender, and well-demarcated skin, with possible blister or bullae formation. It is more common in adults.
Erysipelas is an acute streptococcal infection of the dermis, usually affecting the face or extremities. It initially forms erythematous skin lesions with a sharply demarcated, raised edge, that rapidly enlarge. These may form a red, swollen, warm, hardened, and painful rash, similar in consistency to orange peel.
Ecthyma is similar to impetigo and is caused by staphylococcal or streptococcal infection, but affects deeper layers of the skin.
Candidiasis causes erythematous papules or pustules, or reddened moist plaques, and is usually confined to mucous membranes or areas such as the axilla, groin, between the fingers, and skin folds.
Dermatophytosis causes scaly, red lesions with a slightly raised 'active border' that may contain pustules. It may be vesicular, especially on the feet.
Herpes simplex virus usually affects the lips or genitalia, although other areas of skin may be affected. Vesicles form on an erythematous base that rupture to become erosions covered by crusts.
Varicella (chicken pox and shingles) presents as vesicles on an intensely erythematous base, usually starting on the trunk and spreading to the face and extremities. The vesicles break down to give a crusted appearance similar to impetigo.
Scabies causes intense itching, especially at night. Lesions consist of burrows and small, discrete vesicles, often in finger webs.
Non-infective skin diseases
Atopic eczema presents with dry and itchy skin and is often a secondary cause of impetigo.
Contact dermatitis causes intense itching and reddened, weeping skin. A causative irritant or allergen can sometimes be identified.
Insect bites can cause papule formation which may be confused with impetigo. Lesions may be painful or itchy, and may become super-infected by bacteria to cause secondary impetigo.
Other skin disorders that may be mistaken for impetigo include burns and scalds, drug reactions, Stevens–Johnson syndrome, and toxic epidermal necrolysis.
Rare causes
Discoid lupus erythematosus may present with well-defined plaques on the face, ears, and scalp. Lesions develop as a red, inflamed patch, with a scaling and crusty appearance.
Pemphigus foliaceus is rare but may mimic impetigo with scaling, crusting, or bullae forming a butterfly distribution on the face or on the scalp, chest, and upper back.
Bullous pemphigoid is a benign skin disease most common in older people that is characterized by widespread blistering; it can be confused with bullous impetigo.
Sweet's syndrome is associated with haematological disorder (in particular neutrophilia) and is characterized by the sudden onset of tender or painful plaques or nodules, with occasional pseudo-vesicle or pustule formation, and fever.
Basis for recommendation
Basis for recommendation
This list is derived from narrative reviews [Watkins, 2005; Cole and Gazewood, 2007].
Management
Management
Scenario: Management: covers the management of people with impetigo.
Scenario: Management
Scenario: Management of impetigo
Patient advice
What advice should I give to a person about impetigo?
Provide written information about impetigo. Patient information leaflets can be downloaded from the Health Protection Agency website at www.hpa.org.uk (pdf).
Reassure the person that impetigo usually heals completely without scarring, and that serious complications are rare.
Advise that hygiene measures are important to aid healing and stop the infection spreading to other sites on the body and to other people, and recommend that the person:
Washes the affected areas with soapy water.
Washes the hands after touching a patch of impetigo, and after applying antibiotic cream.
Avoids scratching affected areas, and keeps fingernails clean and cut short.
Avoids sharing towels, flannels, clothing, and bathwater until the infection has cleared.
Children and adults should stay away from school or work until the lesions are dry and scabbed over, or, if the lesions are still crusted or weeping, for 48 hours after antibiotic treatment has started.
Advise the person to attend a follow-up appointment if there is no significant improvement after 7 days.
Basis for recommendation
Basis for recommendation
Information on prognosis
Complications with impetigo, such as streptococcal-mediated glomerulonephritis, are very rare. However, visibly unpleasant lesions, especially on the face, may cause considerable distress for children and parents, so they should be reassured about the temporary nature of the infection [Watkins, 2005].
Advice on hygiene
CKS found no controlled trials that investigated the effectiveness of hygiene practices in stopping the spread of infection or improving healing rates. However, the non-bullous form of impetigo is highly contagious, and these are generally accepted by experts as being appropriate measures [HPA, 1999; Nursing Times, 2004; Watkins, 2005; DTB, 2007].
Absenteeism from school or nursery
This recommendation is based on advice from the Health Protection Agency [HPA, 2010].
After consultation with expert reviewers, CKS infers that the term 'crusting' in this context refers to the scabs that form during the healing process (eschar) rather than the initial gold-crusted plaques typically seen at presentation.
Scab formation, indicating healing, usually occurs within 2 days of starting antibiotic treatment.
It is reasonable to extrapolate this advice to adults.
Treatment failure
Most controlled trials have shown positive results from topical and oral antibiotics after 1 week [George and Rubin, 2003; Koning et al, 2003]. If the condition is not improving after this time, or is deteriorating, it is reasonable to extend treatment, while waiting for bacterial sensitivity data.
Treatment
How should I treat a person with impetigo?
Non-bullous infection requires treatment with topical or oral antibiotics, and management of the underlying cause (if applicable).
For localized infection, treat with topical fusidic acid (three to four times daily, for 7 days).
Before the initial application of topical antibiotics, advise the person (or parent) to remove crusted areas by soaking them in soapy water, as long as this does not cause discomfort.
Topical mupirocin, retapamulin, and antiseptics are not recommended initially.
For extensive infection, areas on which it would be impractical to use topical drugs, or severe infection (including systemic symptoms), treat with an oral antibiotic.
Oral flucloxacillin (four times daily for 7 days) is recommended first-line.
Oral clarithromycin (twice daily for 7 days) or erythromycin (four times daily for 7 days) are alternatives if the person is allergic to penicillins.
The most likely underlying conditions that may be associated with impetigo are atopic eczema, scabies, or head lice. For more information on the management of these conditions, see the CKS topics on Eczema - atopic, Scabies, and Head lice.
Bullous infection usually requires treatment with an oral antibiotic (flucloxacillin or clarithromycin/erythromycin).
Routine follow-up is not required, but advise the person to return if there is no significant improvement 7 days after initiation of treatment (or sooner if the condition is worsening).
Basis for recommendation
Basis for recommendation
Passive treatment
Passive treatment (hygiene measures alone) is not recommended, even for small, localized lesions. Although placebo-controlled trials have shown that untreated impetigo usually resolves in about 2–3 weeks [Koning et al, 2003], topical treatment is effective and has few adverse effects. In addition, untreated impetigo is highly contagious and there is a risk it may become generalized.
Topical treatment
There is good evidence from several placebo-controlled and comparative randomized controlled trials (RCTs) that topical antibiotics are effective in the treatment of localized non-bullous impetigo [George and Rubin, 2003; Koning et al, 2003].
Fusidic acid is recommended first-line. It is effective against Staphylococcus aureus and Streptococcus pyogenes and is licensed for the treatment of impetigo [ABPI Medicines Compendium, 2001]. It has been shown in comparative RCTs to be as effective as mupirocin and retapamulin.
Mupirocin should be reserved for the treatment of impetigo known to be caused by meticillin-resistant Staphylococcus aureus (MRSA) because of concerns over bacterial resistance. This is in line with recommendations from the Health Protection Agency [HPA and Association of Medical Microbiologists, 2008] and the British National Formulary [BNF 64, 2012].
Retapamulin is a newer topical antibiotic that has been shown, in a comparative RCT, to be equivalent in efficacy to fusidic acid [Oranje et al, 2007]. However, it is a black triangle drug (undergoing post-marketing surveillance), and is likely to be more expensive than fusidic acid without offering additional clinical benefit. On this basis, some experts recommend it should be reserved as a second-line treatment [DTB, 2008].
Topical antiseptics are not recommended for the treatment of impetigo, although some specialists advocate the use of hydrogen peroxide cream in some instances. There is limited evidence from a meta-analysis of two RCTs that topical antiseptics are not as effective as topical antibiotics. They can also cause skin reactions, and antiseptics that have an alcoholic base can exacerbate dry and fissured skin [Watkins, 2005].
Removing crusts: there is insufficient evidence from controlled trials to show whether removing the crust from lesions before application of a topical antibiotic improves their efficacy [DTB, 2008]. However, it is believed by some experts that removal of the crust will allow the antibiotic to come into direct contact with the pathogens rather than being wasted on inert, dry, exfoliating skin [Watkins, 2005]. Removal of scabs formed during the healing process is not recommended as it is likely to cause pain, bleeding, and scarring.
Oral antibiotics
The evidence to support the use of oral antibiotics to treat impetigo is limited due to a lack of adequate placebo-controlled trials, although for localized impetigo, comparative RCTs have shown they are probably not as effective as topical antibiotics [George and Rubin, 2003; Koning et al, 2003]. However, for more extensive impetigo, or for impetigo causing systemic symptoms, oral antibiotics are the most practical option. There is little evidence on the treatment of bullous impetigo, but oral antibiotics are thought to be a reasonable option [DTB, 2007].
Flucloxacillin is recommended as first-line treatment for extensive impetigo [HPA and Association of Medical Microbiologists, 2008]. Although there is a lack of evidence from RCTs to prove the efficacy of flucloxacillin, it is known to be effective against Gram-positive organisms, including beta-lactamase producing Staphylococcus aureus [ABPI Medicines Compendium, 2008a], and it demonstrates suitable pharmacokinetics, with good diffusion into skin and soft tissues [Finch et al, 2003].
Erythromycin is a macrolide antibiotic with a broad spectrum of activity, including most staphylococcal and streptococcal species [Finch et al, 2003]. It has been studied relatively extensively in comparative RCTs, and been found to be superior to penicillin, and equivalent to most other antibiotics [Koning et al, 2003].
Clarithromycin is recommended as an alternative macrolide to erythromycin. It is generally considered to cause less adverse effects than erythromycin [DTB, 1991] and although this advantage is mainly theoretical, there are some limited data from RCTs to corroborate this [Aronson, 2006]. In addition, it only requires twice-daily dosing, an important consideration for children of school age.
Follow-up
Most controlled trials have shown positive results from topical and oral antibiotics after 1 week [George and Rubin, 2003; Koning et al, 2003] making routine follow-up unnecessary.
Treatment failure
What should I do if initial treatment is not fully effective?
If lesions are not improving 7 days after initiation of treatment or the condition is worsening:
Review the diagnosis and any underlying cause.
Check compliance with treatment and hygiene measures.
Take a swab.
If topical fusidic acid was used, assess whether the impetigo has spread.
If it has, consider prescribing an oral antibiotic.
If it has not, consider a trial of topical retapamulin (for 5 days; do not use topical antibiotics for longer than 2 weeks).
If an oral antibiotic was used, consider extending treatment for an additional week while waiting for swab results.
For people with recurrent impetigo, consider taking nasal swabs to detect staphylococcal carriage, and additionally consider swabbing the immediate family.
If Staphylococcus aureus is detected, advise on hygiene measures and eliminate the nasal carriage with mupirocin.
For further information, see the section on Staphylococcal carriage in the CKS topic on Boils, carbuncles, and staphylococcal carriage.
Basis for recommendation
Basis for recommendation
CKS found no evidence to guide practice on what to do if initial treatment is not effective; therefore, recommendations are pragmatic.
Treatment failure
Most controlled trials have shown positive results from topical and oral antibiotics after 1 week [George and Rubin, 2003; Koning et al, 2003]. If the condition is not improving after this time, or is deteriorating, it is reasonable to extend treatment, while waiting for bacterial sensitivity data.
Although topical fusidic acid is still regarded as the first-line choice by most specialists, there is increasing evidence from observational studies to suggest that bacterial resistance to it is a growing problem [Ravenscroft et al, 2000; Osterlund et al, 2002; Tveten et al, 2002; O'Neill et al, 2004]. Therefore, if treatment failure occurs with fusidic acid, an alternative such as topical retapamulin should be considered, provided infection has not become widespread.
Switching from flucloxacillin to a different oral antibiotic (for example erythromycin or clarithromycin) is not recommended as this is unlikely to be of benefit. In this situation there is the possibility that the infection is caused by meticillin-resistant Staphylococcus aureus (MRSA) and swabs are necessary to confirm or exclude this.
Retapamulin
Expert opinion from a narrative review recommended that retapamulin is a suitable second-line treatment for people who have not responded to topical fusidic acid [DTB, 2008].
There is evidence from a randomized controlled trial that retapamulin is as effective as fusidic acid in the treatment of impetigo [Oranje et al, 2007].
In contrast to fusidic acid, retapamulin has a relatively broad spectrum of activity. It acts by a different mechanism to other topical antibiotics, and development of bacterial resistance is slow (and, as it is not used systemically, it is of less concern) [Yang and Keam, 2008]. On this basis, retapamulin is a reasonable second-line choice, providing the impetigo has not spread extensively.
It should be noted that the use of retapamulin for longer than 5 days is off licence [ABPI Medicines Compendium, 2008b], and use of topical antibiotics for longer than 2 weeks should be discouraged because of the risk of contact sensitization and development of antibiotic resistance [Yang and Keam, 2008].
Nasal staphylococcal carriage
The recommendation for the detection and subsequent management of nasal staphylococcal carriage is based on expert opinion from CKS reviewers. Studies have shown that nasal carriage of S. aureus increases the risk of developing staphylococcal skin infections such as boils and cellulitis [Ladhani and Garbash, 2005], and it is not unreasonable to suppose there is a similar mechanism occurring with recurrent impetigo.
Referral
When should I refer a person with impetigo?
Referral is rarely necessary. Consider referring to a dermatologist or paediatrician if:
The diagnosis is uncertain (see Differential diagnosis).
There is severe extensive impetigo (possibly with systemic symptoms).
Lesions are unresponsive to maximal treatment in primary care.
Impetigo recurs frequently.
If there is a significant local outbreak (for example in a nursing home or school), contact the local consultant in Communicable Disease Control.
Basis for recommendation
Basis for recommendation
CKS found no evidence to guide management on when it is appropriate to refer a person with impetigo. Therefore these are pragmatic recommendations and reflect the usually benign nature of the infection.
Evidence
Evidence
Supporting evidence
Topical antibiotics
Evidence on topical antibiotics for impetigo
There is evidence from randomized controlled trials (RCTs) that topical fusidic acid and mupirocin are effective in the treatment of localized non-bullous impetigo. Their use in extensive impetigo may be limited by practical issues. There is evidence that a newer topical antibiotic, retapamulin, is as effective as fusidic acid.
A Cochrane systematic review (search date: March 2002) identified 57 RCTs (n = 3533) that investigated a variety of interventions in the treatment of impetigo [Koning et al, 2003]. The primary outcome of these studies was clinical cure or improvement at 1 week, as assessed by the investigator.
The main results were:
A meta-analysis of five placebo-controlled trials in people with non-bullous impetigo found that, overall, topical antibiotics resulted in better cure rates than placebo (odds ratio [OR] 6.49, 95% CI 3.93 to 10.73). Three trials found mupirocin to be more effective than placebo (OR 5.40, 95% CI 2.79 to 10.45), and one trial found fusidic acid to be more effective than placebo (OR 8.65, 95% CI 3.88 to 19.29).
Twelve RCTs compared different topical antibiotics with each other in people with non-bullous impetigo; no significant differences were found.
A meta-analysis of 10 RCTs found mupirocin to be more effective than oral erythromycin (OR 1.76, 95% CI 1.05 to 2.97) in people with non-bullous impetigo. Topical fusidic acid was also found to be superior to erythromycin in one trial.
One RCT in people with bullous impetigo found no significant difference (OR 3.57, 95% CI 0.53 to 23.95) between topical fusidic acid and oral erythromycin.
The authors concluded that topical fusidic acid or mupirocin are superior to oral antibiotics in the treatment of limited impetigo.
Another systematic review (search date: August 2002) identified 16 RCTs that met its inclusion criteria; trials that excluded people on the basis of results from skin swabs were not included in the review [George and Rubin, 2003].
Meta-analysis showed that topical antibiotics were more effective than placebo (OR 2.69, 95% CI 1.49 to 4.86) and were superior to oral erythromycin (OR 0.48, 95% CI 0.23 to 1.00).
On the basis of the available evidence, the authors recommended the use of a topical antibiotic for 7 days for people with limited impetigo.
Topical retapamulin is a newer topical antibiotic, developed and licensed since the above systematic reviews [DTB, 2008].
A placebo-controlled trial (n = 213) found a superior clinical response in people with non-bullous impetigo who received retapamulin compared with vehicle alone (85% compared with 52%, p < 0.0001) [Koning et al, 2008].
An RCT (n = 519), powered to show non-inferiority of the interventions, compared the effectiveness of treatment with retapamulin for 5 days or fusidic acid for 7 days [Oranje et al, 2007].
In those people completing the trial as per protocol, there was a clinical response of 99.1% with retapamulin compared with 94.0% for fusidic acid. This indicated a significant benefit for retapamulin (difference 5.1 percentage points, 95% CI 1.1 to 9.0, p = 0.003).
However, using intent-to-treat analysis, there was no significant difference between the treatments: clinical response 94.8% with retapamulin compared with 90.1% with fusidic acid (difference 4.7 percentage points, 95% CI –0.4 to +9.7, p = 0.062).
Oral antibiotics
Evidence on oral antibiotics for impetigo
The evidence from randomized controlled trials (RCTs) suggests that oral antibiotics offer no advantages compared with topical antibiotics in the treatment of limited impetigo. For more extensive impetigo, the evidence is less conclusive, but oral antibiotics are a more practical option. There is little evidence from RCTs to guide the choice of antibiotic; instead this should consider the antibiotic sensitivities of the likely pathogen, bearing in mind that a narrow-spectrum antibiotic should be used where possible to limit the spread of bacterial resistance and gastrointestinal overgrowth.
A Cochrane systematic review (search date: March 2002) identified 57 RCTs (n = 3533) that investigated a variety of interventions in the treatment of impetigo [Koning et al, 2003]. The primary outcome of these studies was clinical cure or improvement at 1 week, as assessed by the investigator.
In people with non-bullous impetigo:
Only one RCT was identified that compared an antibiotic (penicillin) with placebo; no significant difference was found (odds ratio [OR] 9.26, 95% CI 0.44 to 192.72).
Twenty five RCTs (mostly small and of low methodological quality) compared one oral antibiotic with another, and in general there was little or no difference in outcomes. One trial found cefuroxime to be superior to erythromycin (OR 6.40, 95% CI 1.44 to 28.44). A meta-analysis of two trials found erythromycin to be superior to penicillin (OR 8.82, 95% CI 1.49 to 52.01). A single study found co-amoxiclav to be superior to amoxicillin (OR 9.80, 95% CI 1.09 to 88.23).
When compared with topical antibiotics, a meta-analysis of 10 RCTs found oral erythromycin to be less effective than mupirocin (OR 1.76, 95% CI 1.05 to 2.97). One trial also found erythromycin to be less effective than fusidic acid.
The adverse effects of oral antibiotics were not widely reported, but where they were, they tended to favour topical treatments compared with oral treatments.
The authors concluded that oral antibiotics are not more, and are possibly less, effective than topical antibiotics in the treatment of limited impetigo. However, the relative effectiveness of oral and topical antibiotics in extensive impetigo is unclear.
Another systematic review (search date: August 2002) identified 16 RCTs that met its inclusion criteria; trials that excluded people on the basis of results from skin swabs were not included in the review [George and Rubin, 2003].
Overall, results from trials comparing topical and oral antibiotics were conflicting (some trials excluded people with extensive impetigo), although oral erythromycin was found to be less effective than topical mupirocin (OR 0.48, 95% CI 0.23 to 1.00).
The available trial evidence indicated that cefalexin was marginally superior to erythromycin, while the penicillins were found to be inadequate for the treatment of impetigo.
The authors noted that more research is required into the role of oral antibiotics in the treatment of extensive impetigo, particularly for flucloxacillin.
Current expert opinion recommends that, where possible, narrow-spectrum oral antibiotics that cover the causative pathogens involved in impetigo should be used [DTB, 2007]. This is responsible prescribing, and aims to reduce the incidence of resistant bacteria, such as meticillin-resistant Staphylococcal aureus (MRSA), and overgrowth of Clostridium difficile in the gastrointestinal tract. On the basis of this, flucloxacillin or a macrolide (clarithromycin or erythromycin) are recommended for the treatment of impetigo in the UK [HPA and Association of Medical Microbiologists, 2008].
Topical antiseptics
Evidence on topical antiseptics for impetigo
There is limited evidence from randomized controlled trials (RCTs) to suggest topical antiseptics are not beneficial in the treatment of impetigo.
A Cochrane systematic review (search date: March 2002) identified two RCTs that investigated the effectiveness of disinfectants in the treatment of impetigo [Koning et al, 2003]. The primary outcome of these studies was clinical cure or improvement at one week, assessed by the investigator.
In people with non-bullous impetigo:
One trial (n = 102) found no improvement in either group when treatment with hexachlorophene was compared with placebo. The same study found no difference when hexachlorophene was compared with bacitracin.
One trial (n = 256) compared treatment with hydrogen peroxide with topical fusidic acid. There was a tendency to favour fusidic acid, but this did not quite reach statistical significance (odds ratio [OR] 1.79, 95% CI 0.99 to 3.25). Hydrogen peroxide caused more mild adverse effects (unspecified) than fusidic acid.
When the two studies were combined in a meta-analysis, topical antibiotics proved to be superior to topical antiseptics (OR 1.84, 95% CI 1.03 to 3.29).
The authors concluded that there is little evidence from RCTs to support the use of antiseptics in the treatment of impetigo.
Search strategy
Scope of search
A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of Impetigo.
Search dates
Jan 2006 – Dec 2008
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.
impetigo/, impetigo.tw
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSH subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Topic specific literature search sources
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
National Guidelines Clearinghouse
British Columbia Medical Association
Institute for Clinical Systems Improvement
Guidelines International Network
National Library of Guidelines
National Health and Medical Research Council (Australia)
University of Michigan Medical School
Michigan Quality Improvement Consortium
National Resource for Infection Control
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
DynaMed
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
References
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