In vitro activity of retapamulin against Staphylococcus aureus isolates resistant to fusidic acid and mupirocin.
OBJECTIVE
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.
Woodford
N
N
Antibiotic Resistance Monitoring and Reference Laboratory, HPA Centre for Infections, London NW9 5EQ, UK. neil.woodford@hpa.org.uk
Afzal-Shah
M
M
Warner
M
M
Livermore
D M
DM
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D004252:DNA Mutational Analysis; D004224:Diterpenes; D024881:Drug Resistance, Bacterial; D005672:Fusidic Acid / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000494:pharmacology*; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000235:genetics; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D006113:United Kingdom
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004224:Diterpenes; C000716547:RPL3 protein, human; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; C508887:retapamulin; D005672:Fusidic Acid; D016712:Mupirocin