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-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 MIC 90 against 234 Staphylococcus aureus isolates and 110 coagulase-negative staphylococci was 0.12 g/ml. Retapamulin MIC 90 s ranged from 0.03 to 0.06 g/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 g/ml. Retapamulin had very little activity against 151 gramnegative bacilli and most of the Enterococcus species tested. Based on the data from this study, for staphylococci, MICs of <0.5, 1, and >2 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 g/ml with a corresponding disk diffusion value of >15 mm can be proposed for susceptible-only microbiological cutoffs.

Dissemination of a pSCFS3-Like cfr -Carrying Plasmid in Staphylococcus aureus and Staphylococcus epidermidis Clinical Isolates Recovered from Hospitals in Ohio

“…Retapamulin MIC results were interpreted according to the microbiological breakpoints proposed by Traczewski and Brown (i.e., Յ0.5 g/ml for susceptibility, 1 g/ml for intermediate, and Ն2 g/ml for resistant) (26). The tigecycline breakpoint for susceptibility was that for S. aureus (Յ0.5 g/ml) approved by the FDA (27 (Fig.…”

“…MIC interpretations were applied as described in CLSI document M100-S22 (25), except in the cases of retapamulin and tigecycline. MIC results for retapamulin and tigecycline compounds were interpreted according to the epidemiological cutoff values for S. aureus proposed by Traczewski and Brown (i.e., Յ0.5 g/ml for susceptible, 1 g/ml for intermediate, and Ն2 g/ml for resistant) and the FDA (Յ0.5 g/ml for susceptible), respectively (26,27).…”

No Decrease in Susceptibility to NVC-422 in Multiple-Passage Studies with Methicillin-Resistant Staphylococcus aureus, S. aureus, Pseudomonas aeruginosa, and Escherichia coli

“…Ciprofloxacin was selected as a broad-spectrum comparator. Mupirocin, fusidic acid, and retapamulin were selected as comparators against MRSA, as these antibiotics are used for the treatment of topical infections (6,18,19).…”

First Report of Staphylococcal Clinical Isolates in Mexico with Linezolid Resistance Caused by cfr : Evidence of In Vivo cfr Mobilization

“…Retapamulin MIC results were interpreted according to parameters reported by Traczewski et al (19). S, susceptible; I, intermediate; R, resistant.…”

“…Isolates were tested for susceptibility by the reference broth microdilution method (1). MIC interpretations were performed based on Clinical and Laboratory Standards Institute criteria (2), except for retapamulin MIC values (19). Quality control strains included Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 (2).…”