Quality control guidelines for susceptibility testing of retapamulin (SB-275833) by reference and standardized methods.

Journal of Clinical Microbiology (Impact Factor: 4.07). 01/2006; 43(12):6212-3. DOI:10.1128/JCM.43.12.6212-6213.2005
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    ABSTRACT: MIC and disk diffusion quality control (QC) ranges were established for two new pleuromutilin antimicrobials (BC-3205 and BC-3781) in an eight-laboratory study performed according to Clinical and Laboratory Standards Institute M23-A3 guidelines. Staphylococcus aureus ATCC 29213 and 25923, Streptococcus pneumoniae ATCC 49619, and Haemophilus influenzae ATCC 4927 strains were evaluated. The proposed QC ranges would aid clinical laboratories in testing these compounds following their development for treatment of respiratory and cutaneous infections.
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    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.
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    ABSTRACT: Retapamulin is a new topical pleuromutilin antibiotic for the treatment of skin and skin-structure infections, including impetigo. In vitro studies indicate that retapamulin has a unique mode of action that minimizes the potential for target-specific cross-resistance with other antibacterials and a limited potential for resistance development. Its spectrum of activity includes the most likely causative pathogens Staphylococcus aureus and Streptococcus pyogenes. In the Global Surveillance Program, retapamulin was highly active in vitro, including against strains of S. aureus resistant to methicillin, mupirocin or fusidic acid. In clinical studies, retapamulin was noninferior to fusidic acid and oral cefalexin, achieving per-pathogen success rates of 86-99%. Topical retapamulin has a good safety profile and is associated with high patient compliance.
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James E Ross