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JAC Advance Access published online on June 19, 2008

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn266
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

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

N. Woodford*, M. Afzal-Shah, M. Warner and D. M. Livermore

Antibiotic Resistance Monitoring and Reference Laboratory (ARMRL), HPA Centre for Infections, London NW9 5EQ, UK

Received 27 May 2008; returned 4 June 2008; revised 1 June 2008; accepted 5 June 2008


* Corresponding author. Tel: +44-20-8327-7255; Fax: +44-20-8327-6264; E-mail: neil.woodford{at}hpa.org.uk

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–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 ≤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.

Key Words: S. aureus , MRSA , mechanisms


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