In vitro activity of retapamulin against Staphylococcus aureus isolates resistant to fusidic acid and mupirocin

Neil Woodford, M. Afzal-Shah, Marina Warner, David Livermore

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46 Citations (Scopus)

Abstract

Objectives: 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-Hintonagar 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 ≤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 ≤0.5 mg/L against S. aureus.

Original languageEnglish
Pages (from-to)766-768
Number of pages3
JournalJournal of Antimicrobial Chemotherapy
Volume62
Issue number4
DOIs
Publication statusPublished - 2008

Keywords

  • MRSA
  • Mechanisms
  • S. aureus

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