JAC Advance Access originally published online on March 9, 2007
Journal of Antimicrobial Chemotherapy 2007 59(4):646-651; doi:10.1093/jac/dkm019
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In vitro activity against anaerobes of retapamulin, a new topical antibiotic for treatment of skin infections
1 Faculty of Pharmacy, 3 rue du Professeur Laguesse, BP83, 59006 Lille Cedex, France 2 Bichat Hospital, Paris, France
Received 13 September 2006; returned 20 November 2006; revised 27 December 2006; accepted 11 January 2007
* Corresponding author. Tel: +33-3-20-96-40-43; Fax: +33-3-20-95-90-09; E-mail: marie-francoise.odou{at}univ-lille2.fr
Objectives: Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections. The aim of this study was to determine the antimicrobial activity of retapamulin by determining the minimal inhibitory concentration (MIC) values of this new drug and comparators against a wide range of anaerobic bacteria of human origin.
Methods: The in vitro activity of retapamulin and six comparators (amoxicillin, amoxicillin/clavulanic acid, ceftriaxone, imipenem, clindamycin and metronidazole) was evaluated against 232 anaerobic clinical isolates. MICs were determined by the CLSI reference agar dilution method (M11-A6).
Results: Ceftriaxone, clindamycin and amoxicillin/clavulanic acid resistance rates were 54%, 42% and 9.6%, respectively, within the Bacteroides fragilis group. Despite high resistance rates to various antibiotics, retapamulin inhibited 37/52 (71%) strains of the B. fragilis group and 85/87 (98%) of the other Gram-negative bacilli at a concentration of 2 mg/L or less. All the investigated strains of Clostridium perfringens were inhibited by 1 mg/L retapamulin. Three strains of C. difficile and one strain of C. clostridioforme demonstrated decreased susceptibility to retapamulin. Based on inhibitory concentrations, retapamulin was more active than clindamycin, metronidazole and ceftriaxone against Propionibacterium acnes and anaerobic Gram-positive cocci, as all isolates were inhibited by 
2 mg/L.
Conclusions: At 2 mg/L, retapamulin inhibited 90% of all 232 anaerobes tested, whereas overall resistance rates for the comparators were as follows: co-amoxiclav, 2%; metronidazole, 12%; clindamycin, 15% and ceftriaxone, 20%. The broad anaerobic spectrum demonstrated by retapamulin in vitro is attractive. Pending further clinical investigation, retapamulin may offer an alternative treatment for anaerobic skin infections in this era of increasing resistance.
Keywords: pleuromutilins , skin infections , antianaerobic activity