Proposed MIC and Disk Diffusion Microbiological Cutoffs and Spectrum of Activity of Retapamulin, a Novel Topical Antimicrobial Agent

Retapamulin, the first pleuromutilin antimicrobial agent approved for the topical treatment of skin infections in humans, was tested against 987 clinical isolates representing 30 species and/or resistance groups. MICs were determined along with disk diffusion zone diameters using a 2-mu g disk. Population distribution and MIC versus disk zone diameter scattergrams were analyzed to determine microbiological MIC cutoff values and inhibition zone correlates. Minimum bactericidal concentrations were performed on a smaller subset of key species. The retapamulin MIC90 against 234 Staphylococcus aureus isolates and 110 coagulase-negative staphylococci was 0.12 mu g/ml. Retapamulin MIC(90)s ranged from 0.03 to 0.06 mu g/ml against beta-hemolytic streptococci including 102 Streptococcus pyogenes, 103 Streptococcus agalactiae, 59 group C Streptococcus, and 71 group G Streptococcus isolates. The MIC90 against 55 viridans group streptococci was 0.25 mu g/ml. Retapamulin had very little activity against 151 gram-negative bacilli and most of the Enterococcus species tested. Based on the data from this study, for staphylococci, MICs of <= 0.5, 1, and >= 2 mu g/ml with corresponding disk diffusion values of >= 20 mm, 17 to 19 mm, and <= 16 mm can be proposed for susceptible, intermediate, and resistant microbiological cutoffs, respectively. For beta-hemolytic streptococci, a susceptible-only MIC of <= 0.25 mu g/ml with a corresponding disk diffusion value of >= 15 mm can be proposed for susceptible-only microbiological cutoffs.