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Retapamulin (ALTABAX ), A New Topical Antimicrobial
By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
The FDA recently approved retapamulin (ALTABAX ) for topical treatment of impetigo due to Staphylococcus aureus and Streptococcus pyogenes in adults and in children 9 months of age or greater. Retapamulin is the first approved representative of a novel class of antimicrobials, the pleuromutilins. It interacts with the 50S subunit of the bacterial ribosome at a binding site that involves protein L3 and inhibits peptidyl transferase, thus preventing the formation of active 50S subunits with resultant inhibition of protein synthesis. In addition to being active against S. aureus and S. pyogenes, retapamulin has in vitro activity against many anaerobes and Propionibacterium species. Methicillin resistance does not affect the in vitro susceptibility of S. aureus to retapamulin. In clinical trials, however, in vitro susceptibility did not correlate with clinical success rates in patients infected with methicillin-resistant S. aureus (MRSA).
Reduced susceptibility of S. aureus to retapamulin can be achieved by serial passage in vitro, but requires the accumulation of multiple mutations in rp1C which encodes the L3 protein. Triple mutants, however, demonstrate impaired growth in vitro. Reduced susceptibility may also result from increased drug efflux.
Clinical trials have demonstrated superiority of retapamulin over topical placebo in the treatment of impetigo. In addition, studies have demonstrated non-inferiority versus orally administered cephalexin in secondarily infected traumatic lesions of skin1 and in secondarily infected dermatitis.2 It is well tolerated and has minimal absorption. It is Pregnancy Category B.
Retapamulin is supplied in 5, 10, and 15 gram tubes. It is applied in a thin layer to a maximum of 100 cm2 in adults and 2% of body surface area in pediatric patients twice daily for 5 days. The cost of 15 grams of retapamulin is reported to be $68 while that of 22 grams of mupirocin is $50.