Stan Block, MD, FAAP

A new topical antibiotic, retapamulin 1% ointment (Altabax; GlaxoSmithKline), has been approved for the treatment of impetigo in adults and children. Retapamulin is indicated for the treatment of localized impetigo caused by susceptible strains of Staphylococcus aureus or Streptococcus pyogenes.

Impetigo, a very contagious infection of the superficial skin (Photo, at right), is the most common bacterial skin infection in children but can occur at any age. As with other types of skin infections, the elderly are more susceptible than younger adults to becoming infected with impetigo. In this common infection, lesions develop at the site of a minor trauma to the skin. Adult patients tend to present days, or even weeks, after the development of pruritic vesicular lesions.

Retapamulin belongs to a new class of antibiotics called pleuromutilins, which are produced by fungi. "It works by binding to a unique site of the ribosome, which is one of the internal workings of a bacterial cell," says Stan Block, MD, FAAP.

S aureus is responsible for about 75% to 80% of cases of impetigo, and the remainder is caused by S pyogenes (group A beta-hemolytic streptococcus). Until now, mupirocin 2% ointment (Bactroban, Centany) was the mainstay of topical therapy, but the introduction of this new antibiotic class offers new treatment options, especially in the face of increasing treatment resistance. "Both retapamulin and mupirocin 2% ointment provide fairly good coverage," says Dr Block, who is professor of clinical pediatrics, University of Louisville and University of Kentucky College of Medicine, Lexington, Ky.

Impetigo in a 25-year-old man.

"But retapamulin has major advantages over mupirocin. You apply it twice a day for 5 days, and you're finished." In contrast, mupirocin must be applied 3 or 4 times a day for up to 12 days. "So it's a shorter course with retapamulin, quicker effects, and easier compliance," he says.

The Changing Face of Impetigo

Impetigo "commonly starts with a big bullous lesion, but we as clinicians rarely see that stage," Dr Block notes. Patients are usually seen after the bullous has popped, when they have honey-colored/crusted, or red and weeping-like lesions. However, "lately, a lot of impetigo looks like an eczema-type rash," he adds.

In fact, eczema may be a common precipitant of impetigo. It can be hard to distinguish whether the eczema is just getting redder, or if it is infection. "A lot of time, physicians will treat it with topical steroids or topical antiinflammatory creams, and then they observe no response at all after a few days." This is an indication of secondary infection, "which is probably impetigous-type lesions." These patients can benefit from retapamulin, if the area is small enough.

Complications are uncommon with superficial impetigo, since it usually remains localized to the skin. "If the impetigo is caused by S pyogenes, rarely acute glomerulonephritis can occur in adults as well as children, if the impetigo is not treated appropriately or not treated at all," says Dr Block. However, although the glomerulonephritis can be serious, most patients will recover.

Retapamulin: Superior Safety

Results of a phase 3 study presented at this year's annual meeting of the American Academy of Dermatology showed that retapamulin was highly effective against both S aureus and S pyogenes, including strains resistant to existing antimicrobial agents.

The trial included 210 patients, aged 9 months to 73 years, 82% of whom were culture positive at baseline. They were randomized to retapamulin ointment, applied twice daily for 5 days, or to placebo. Clinical success rates were significantly better with retapamulin than with placebo (Table). Overall, the response was 85.6% in the retapamulin intent-to-treat group and 52.1% in the placebo group.

In addition, there was a 56.7% difference in clinical success rate compared with placebo among patients who had S aureus strains that were resistant to fusidic acid (not available in the United States) at baseline.

The safety of retapamulin has been evaluated in 2115 adults and children aged ≥9 months who were treated with at least 1 dose of retapamulin compared with 819 adults and children who were treated with at least 1 dose of oral cephalexin (Keflex), and 71 patients who received placebo. Overall, drug-related adverse events occurred in 5.5% of patients receiving retapamulin, 6.6% receiving cephalexin, and 2.8% receiving placebo.

Retapamulin is considered safe and effective for the treatment of elderly patients, based on clinical trials experience with 234 patients aged ≥65 years who were treated with this topical agent.

Indications, Side Effects

Retapamulin is indicated for the topical treatment of impetigo caused by methicillin-susceptible S aureus isolates or by S pyogenes in adults and children aged ≥9 months. It should be used only for localized impetigo, covering up to 100 cm² in total area in adults or up to 2% of the total body surface area in children.

To prevent the development of drug resistance, as well as to maintain the efficacy of retapamulin and other antibacterial agents, its use should be confined to the treatment or prevention of infections that are either proven by culture or strongly suspected of being caused by susceptible bacteria.

Patients should be instructed to apply a thin layer of retapamulin to the affected area twice daily for 5 days. Although the treated area does not need to be covered, patients may use a sterile bandage or gauze dressing.

Among the 1527 adults treated with retapamulin in phase 3 studies, headache was the most frequently reported adverse event (2%), followed by application-site irritation (1.6%) and diarrhea (1.4%). Nausea and nasopharyngitis were each reported by 1.2% of treated patients.

Because of the limited systemic exposure after topical application, dosage adjustments are unnecessary when coadministered with cytochrome (CY) P450-3A4 inhibitors, such as ketoconazole (Nizoral). Retapamulin should have little effect on the metabolism of other CYP450 substrates.

Treatment Recommendations

"When choosing a treatment, the extent of disease is very significant," Dr Block emphasizes. "If you have a small area—less than 2 to 5 inches and less than 7 or 10 spots—then you can usually use the topicals," he says. "The maximum area that should be treated with retapamulin is up to 10 x 10 cm, which is about 4 x 4 inches."

Two meta-analyses (Cochrane Database Syst Rev. 2004;[2]:CD00 3261; Br J Gen Pract. 2003;53:480-487) that looked at a combined total of 73 randomized controlled trials involving more than 5000 patients concluded topical therapy was at least as good as—and in some cases, better than—oral antibiotic therapy in patients with limited impetigo.

And in their 2005 guidelines for the treatment of skin and soft-tissue infections, the Infectious Diseases Society of America (IDSA) recommends topical rather than oral treatment for patients with limited lesions (Clin Infect Dis. 2005;41:1373-1406).

For disease that covers a wide range of skin, with multiple impetigous lesions around the nose, the buttocks, and elsewhere, "It's too cumbersome to use topical agents, and you have to use oral antibiotics." For patients with extensive disease, many physicians use both topical and oral treatments. "The topical agents are used to cut down the contagiousness quicker during the first few days," says Dr Block.

The IDSA guidelines cite mupirocin as the best available topical therapy, but this was before the approval of this new class of antibiotics. Moreover, considerable resistance to mupirocin is increasingly being reported, with a prevalence ranging from 5% to 15%. "Resistance to mupirocin is increasing, and it's becoming more worrisome lately," observes Dr Block.

While cautioning that there are not enough data to make a claim that retapamulin will work in mupirocin-resistant impetigo, he says, "The thinking is that it will work."