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In vitro activity of retapamulin against Staphylococcus aureus isolates resistant to fusidic acid and mupirocin Woodford N; Afzal-Shah M; Warner M; Livermore DMJ Antimicrob Chemother 2008[Oct]; 62 (4): 766-8OBJECTIVES: We determined the in vitro activity of retapamulin, a novel pleuromutilin antibiotic, against 664 Staphylococcus aureus isolates from the UK, including many resistant to fusidic acid and/or highly resistant to mupirocin. METHODS: MICs were determined on Mueller-Hinton agar in accordance with the CLSI guidelines. Susceptibility was categorized using CLSI criteria, where available; otherwise the European Committee for Antimicrobial Susceptibility Testing (EUCAST)/BSAC criteria were used (for mupirocin and fusidic acid). Mutations in the rplC gene, which encodes ribosomal protein L3, were sought by PCR and DNA sequencing. RESULTS: The S. aureus included 488 (73%) methicillin-resistant isolates (oxacillin MICs >2 mg/L), 336 isolates (51%) resistant to fusidic acid (MICs >1 mg/L) and 254 (38%) with high-level mupirocin resistance (MICs >256 mg/L); 103 (16%) isolates were resistant both to fusidic acid and to high levels of mupirocin. Retapamulin inhibited 663 (99.9%) isolates at < or =0.25 mg/L. A single methicillin-resistant S. aureus isolate, also with high-level mupirocin resistance, required a retapamulin MIC of 2 mg/L, but its reduced susceptibility to retapamulin was not associated with any mutation in ribosomal protein L3. CONCLUSIONS: Retapamulin demonstrated excellent activity in vitro against S. aureus isolates, irrespective of their level of resistance to other antibacterials. These results support the EUCAST epidemiological cut-off value for retapamulin of < or =0.5 mg/L against S. aureus.|*Drug Resistance, Bacterial[MESH]|Anti-Bacterial Agents/*pharmacology[MESH]|Bacterial Proteins/genetics[MESH]|Bridged Bicyclo Compounds, Heterocyclic/*pharmacology[MESH]|DNA Mutational Analysis[MESH]|Diterpenes[MESH]|Fusidic Acid/*pharmacology[MESH]|Humans[MESH]|Microbial Sensitivity Tests[MESH]|Mupirocin/*pharmacology[MESH]|Ribosomal Protein L3[MESH]|Ribosomal Proteins/genetics[MESH]|Staphylococcal Infections/microbiology[MESH]|Staphylococcus aureus/*drug effects/isolation & purification[MESH]|United Kingdom[MESH] |
