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-μg 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 234Staphylococcus aureus isolates and 110 coagulase-negative staphylococci was 0.12 μg/ml. Retapamulin MIC90 s ranged from 0.03 to 0.06 μg/ml against beta-hemolytic streptococci including 102Streptococcus pyogenes , 103Streptococcus agalactiae , 59 group CStreptococcus , and 71 group GStreptococcus isolates. The MIC90 against 55 viridans group streptococci was 0.25 μg/ml. Retapamulin had very little activity against 151 gram-negative bacilli and most of theEnterococcus species tested. Based on the data from this study, for staphylococci, MICs of ≤0.5, 1, and ≥2 μg/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 μg/ml with a corresponding disk diffusion value of ≥15 mm can be proposed for susceptible-only microbiological cutoffs.