Topical retapamulin in the management of infected traumatic skin lesions

Abstract

Retapamulin is a novel semisynthetic pleuromutilin antibiotic specifically designed for use as a topical agent. The unique mode of action by which retapamulin selectively inhibits bacterial protein synthesis differentiates it from other nonpleuromutilin antibacterial agents that target the ribosome or ribosomal factors, minimizing the potential for target-specific cross-resistance with other antibacterial classes in current use. In vitro studies show that retapamulin has high potency against the Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes, and coagulase-negative staphylococci) commonly found in skin and skin-structure infections (SSSIs), including S. aureus strains with resistance to agents such as macrolides, fusidic acid, or mupirocin, and other less common organisms associated with SSSIs, anaerobes, and common respiratory tract pathogens. Clinical studies have shown that twice-daily topical retapamulin for 5 days is comparable to 10 days of oral cephalexin in the treatment of secondarily infected traumatic lesions. A 1% concentration of retapamulin ointment has been approved for clinical use as an easily applied treatment with a short, convenient dosing regimen for impetigo. Given the novel mode of action, low potential for cross-resistance with established antibacterial agents, and high in vitro potency against many bacterial pathogens commonly recovered from SSSIs, retapamulin is a valuable enhancement over existing therapeutic options.

Figure 1

In multi-step studies, increased minimum inhibitory concentrations (MICs) to retapamulin were seen among Staphylococcus aureus isolates, but required more passages compared with mupirocin or fusidic acid; figure shows a summary of the 12 S. aureus isolates tested. Drawn from data of Kosowska-Shick et al.

Figure 2

Clinical success rates at follow-up in the per-protocol clinical populations from randomized controlled clinical trials comparing topical retapamulin, 1%, twice daily for 5 days, with placebo in the treatment of impetigo and oral cephalexin, 500 mg, twice daily for 10 days, in the treatment of secondarily infected traumatic lesions (SITLs) and secondarily infected dermatitis (SID). Drawn from data of Koning et al, Free et al, and Parish et al.

Figure 3

Compliance with retapamulin was greater than that for cephalexin in patients with secondarily infected traumatic lesions treated with topical retapamulin, 1%, twice daily for 5 days, or with oral cephalexin, 500 mg, twice daily for 10 days; figure shows pooled data from two identical randomized controlled clinical trials (Study 030A and 030B) for intent-to-treat patients who were 80%–120% compliant with study treatment. For secondarily infected dermatitis (Study 032), there was no difference in compliance between the two treatment arms. Patients ≥13 years of age received cephalexin capsules; those who were younger received cephalexin suspension. Drawn from data of GlaxoSmithKline.

Figure 4

Patients with secondarily infected dermatitis treated with topical retapamulin, 1%, twice daily for 5 days, or with oral cephalexin, 500 mg, twice daily for 10 days, recorded a marked preference for topical therapy over oral therapy in both treatment arms. Drawn from data of Parish et al.