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New topical offers a choice in impetigo treatment
Retapamulin is first commercially available antibiotic in pleuromutilin class.
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Impetigo is among the most common bacterial skin infections affecting infants and children, yet questions remain about the most effective drug therapy. This month’s Pharmacology Consult will review the pharmacotherapy of impetigo, to coincide with our special focus section on pediatric dermatology.
A review of impetigo
As a quick review, impetigo exists in two forms – bullous and nonbullous.
About 70% of cases of pediatric impetigo occur as the nonbullous form. Bullous impetigo is recognized by bullae, or blisters.
Bacterial causes of impetigo include Staphylococcus aureus and Streptococcus pyogenes. Nonbullous impetigo results from infection with both of these organisms, although S. aureus is increasingly the predominant pathogen. Bullous impetigo results from infection with S. aureus. Impetigo is usually limited to the skin with no systemic symptoms. Neonatal impetigo more commonly includes systemic symptoms. Impetigo typically results from a break in the skin, such as from a minor abrasion or insect bite. The face, neck, and limbs are most commonly involved.
Pharmacotherapy
The most effective drug therapy for impetigo has not been well-established. Controversy remains about the need for antibiotics, the role of topical vs. oral antibiotics, and which specific antibiotics are most effective.
Since impetigo is generally self-limiting, antibacterial therapy is not always necessary. Although impetigo is limited to the skin, there is some concern that because streptococcal infections may potentially result in glomerulonephritis, antibiotic treatment is necessary. However, it has not been established that the use of antibiotics for the treatment of impetigo prevents glomerulonephritis.
A variety of topical and oral antibiotics can be used for impetigo therapy. Mupirocin (Bactroban, GlaxoSmithKline and generic versions) is commonly recommended. The 2006 Red Book recommends mupirocin or bacitracin for topical treatment, and oral antibiotic therapy (anti-staphylococcal 
-lactams, 1st/2nd-generation cephalosporins) when infection is widespread or when impetigo occurs in multiple family members or childcare groups. Textbooks and review articles similarly recommend mupirocin as initial treatment for impetigo.
Mupirocin, unrelated to other antibiotics, inhibits bacterial protein synthesis and demonstrates good activity toward S. pyogenes and several staphylococcal species, including S. aureus (-lactamase resistant and methicillin-resistant). Mupirocin ointment is labeled for use to treat impetigo in children aged 2 months to 16 years. Mupirocin is dosed three times daily for eight days. Mupirocin is also available in a cream formulation, indicated for treatment of secondarily infected traumatic skin lesions.
The Cochrane Database of Systematic Reviews discussed impetigo treatment and published its findings in 2003. Randomized trials were evaluated using two scoring methods. Fifty-seven trials were assessed, comparing 38 different treatments. Several studies compared mupirocin to oral antibiotics (such as cephalexin and dicloxacillin), with no significant difference in cure rates in children with limited disease. Researchers conducting this review concluded that good evidence exists to suggest that mupirocin is at least as efficacious as oral antibiotics for impetigo. As most studies excluded children with extensive infection, no conclusions could be reached about the comparative efficacy and role of oral antibiotics as compared with mupirocin in children with extensive disease. Most references recommend the use of oral antibiotic therapy in children with extensive impetigo. Other topical antibiotics, such as bacitracin, were found to be less effective than mupirocin. Limited evidence evaluating the use of disinfecting agents like hexachlorophene suggest that these agents serve no beneficial role as sole or adjunctive treatment.
A new topical
Retapamulin 1% ointment (Altabax, GlaxoSmithKline) was approved by the FDA in April 2007 and is labeled for use in children aged 9 months and older for the treatment of impetigo due to susceptible strains of S. aureus and S. pyogenes.
Retapamulin is the first commercially available antibiotic of the pleuromutilin class. Its mode of action includes inhibition of bacterial protein synthesis in a mechanism distinct from other antibiotics. The phase-3 study used for the FDA labeling of the ointment has not been published in the medical literature. Information available from the package insert indicates that Altabax demonstrated an efficacy rate of 85.6% in children with impetigo, which was significantly greater than placebo. Retapamulin is dosed twice daily for five days.
Antibiotic selection
Most experts recommend mupirocin topical ointment for children with limited impetigo. Evidence from published trials supports this recommendation as mupirocin has demonstrated efficacy greater than other topical antibiotics and similar efficacy as several oral antibiotics for limited disease. Textbooks and published review articles recommend the use of oral antibiotics, such as cephalexin, when impetigo is extensive or systemic manifestations exist.
If methicillin-resistant S. aureus is suspected or cultured, trimethoprim/sulfamethoxazole or clindamycin are appropriate initial antibiotics to prescribe. However, evidence from published clinical trials does not exist to support this practice, although it seems reasonable. The use of a topical ointment on a child with multiple or extensive lesions may not be practical, however. The use of multiple ointment tubes in such a child may incur significant costs. An oral antibiotic is likely to be significantly less expensive. Disadvantages with oral antibiotic use include a greater potential for systemic adverse events, such as loose stools or diarrhea, which are unlikely from a topically-applied antibiotic.
Retapamulin 1% ointment is a newly available topical antibiotic labeled for use in children with impetigo. As no direct trials have been conducted with retapamulin and mupirocin, their comparative efficacy cannot be assessed. Altabax may be more convenient to use than mupirocin, as the ointment is dosed twice daily for five days, as compared with three times daily dosing for a duration of eight days for mupirocin. Disadvantages of Altabax include its labeled indication for methicillin-susceptible S. aureus only, its cost, relative to generic mupirocin, and a lack of clinical experience, as compared with mupirocin (table).
For more information:
- Cole C. Diagnosis and treatment of impetigo. American Family Physician 2007;75:859-64.
- Koning S. Interventions for impetigo. Cochrane Database of Systematic Reviews 2003(2):CD003261.
- George A. A systematic review and meta-analysis of treatments for impetigo. British Journal of General Practice 2003;53:480-7.