title: Proposed MIC and disk diffusion microbiological cutoffs and spectrum of activity of retapamulin, a novel topical antimicrobial agent.
abstract: 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-microg 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 MIC(90) against 234 Staphylococcus aureus isolates and 110 coagulase-negative staphylococci was 0.12 microg/ml. Retapamulin MIC(90)s ranged from 0.03 to 0.06 microg/ml against beta-hemolytic streptococci including 102 Streptococcus pyogenes, 103 Streptococcus agalactiae, 59 group C Streptococcus, and 71 group G Streptococcus isolates. The MIC(90) against 55 viridans group streptococci was 0.25 microg/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 <or=0.5, 1, and >or=2 microg/ml with corresponding disk diffusion values of >or=20 mm, 17 to 19 mm, and <or=16 mm can be proposed for susceptible, intermediate, and resistant microbiological cutoffs, respectively. For beta-hemolytic streptococci, a susceptible-only MIC of <or=0.25 microg/ml with a corresponding disk diffusion value of >or=15 mm can be proposed for susceptible-only microbiological cutoffs.
authors: The Clinical Microbiology Institute, Inc, Wilsonville, OR 97070, USA. mtrac@clinmicroinst.com
authors: Maria M
authors: MM
authors: Traczewski
authors: Steven D
authors: SD
authors: Brown
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage*; D052978:Disk Diffusion Antimicrobial Tests / Q000379:methods; D004224:Diterpenes; D024881:Drug Resistance, Bacterial; D016983:Enterococcus / Q000187:drug effects / Q000302:isolation & purification; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests / Q000379:methods*; D016712:Mupirocin / Q000008:administration & dosage; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D013291:Streptococcus / Q000145:classification / Q000187:drug effects / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004224:Diterpenes; C508887:retapamulin; D016712:Mupirocin