Retapamulin 1% ointment

Abstract Background Colonization with Staphylococcus aureus, particularly MRSA, is a crucial risk factor for subsequent infection. Decolonization measures are often undertaken to prevent recurrent MRSA infection and transmission; however, increasing rate of resistance to the gold standard mupirocin has been noted globally. At our institution, there is >85% high-level resistance to mupirocin among strains from a geographically defined genotypic cluster of CA-MRSA in children from Orthodox communities in Brooklyn. Retapamulin is a topical bacteriostatic pleuromutilin antibiotic that has demonstrated excellent in vitro activity against mupirocin-resistant isolates from pediatric patients with MRSA infection presenting to our institution suggesting that it may be a promising alternative decolonization therapy. We sought to determine the efficacy of retapamulin as a topical decolonizing agent against mupirocin-resistant MRSA among the identified high-risk Brooklyn cluster via a randomized, placebo-controlled, double-blinded phase three trial. Methods Children aged 9 months-17 years who resided in high-risk zip codes used as a proxy for Orthodox Jewish predominant neighborhoods were recruited either from inpatient units at NYU Langone or at a partnered community clinic. Participants were screened via nasal and rectal culture to detect MRSA colonization. Enrolled participants were randomized to receive either retapamulin or placebo and instructed to apply the ointment nasally and rectally twice a day for 5 days. Repeat nasal and rectal swab cultures were collected one week and one month after completion of topical therapy to assess MRSA colonization status. The change in colonization rates was assessed via Fisher’s exact test. Results 173 participants were screened from December 2017 to March 2019 in which 47 ultimately underwent randomization (23 in the retapamulin group and 24 in the placebo group). The median age was 3.9 years (SD 3.5 years). Children in the placebo group were 15.2 times more likely to be colonized with MRSA after one week of the decolonization protocol compared with the retapamulin group (OR 15.2, CI 2.8–81, P = 0.0004). However, children in the placebo group were only 1.1 times more likely to be colonized with MRSA after one month compared with the retapamulin group (OR 1.1, CI 0.3–3.9, P = 1). (*Full data analysis currently in progress with additional results available soon.) Conclusion In this small pilot randomized trial, children who received retapamulin had a significantly lower rate of MRSA colonization and higher rates of clearance compared with placebo at one week post decolonization, but no significant difference at the one month mark. These data suggest that retapamulin is a promising alternative short-term nasal and peri-rectal decolonzing therapy in order to prevent infections and the spread of this mupirocin-resistant MRSA clone among pediatric patients in this affected community and our hospital. Disclosures All authors: No reported disclosures.

Abstract licence: CC BY-NC-ND 4.0

: Retapamulin is one of the antibiotics recently developed semi-synthetically to inhibit protein synthesis in a specific manner different from other antibiotics. This pleuromutilin derivative shows magnificent anti-bacterial activity in Gram-positive pathogens, especially Staphylococcus aureus and Streptococcus pyogenes, and now it is available in ointment formulations (1%) for clinical use with negligible side effects. Despite the low potential for resistance development, antimicrobial susceptibility rates are significantly high. This is especially important when the prevalence of mupirocin-resistant strains is increasing, and the need for new alternatives is urgent. Unfortunately, due to its oxidation by cytochrome p450, this drug cannot be used systemically. However, another pleuromutilin derivative with systemic use, lefamulin, was approved in August 2019 by the US Food and Drug Administration. In addition to pharmacokinetic features, financial issues are also barriers to consider in the progress of new antimicrobials. In this review, we attempt to take a brief look at the derivatives usable in humans and explore their structures, action mode, metabolism, possible ways of resistance, resistance rates, and their clinical use to explain and highlight the valuable points of these antibiotics.

Abstract licence: CC BY-NC 4.0