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

Received 27 May 2008; returned 1 June 2008; revised 4 June 2008; accepted 5 June 2008Objectives: We determined the in vitro activity of retapamulin, a novel pleuromutilin antibiotic, against664 Staphylococcus aureus isolates from the UK, including many resistant to fusidic acid and/orhighly 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 forAntimicrobial Susceptibility Testing (EUCAST)/BSAC criteria were used (for mupirocin and fusidic acid).Mutationsinthe rplCgene,whichencodesribosomalproteinL3,weresoughtbyPCRandDNAsequencing.Results:TheS. aureus included 488 (73%) methicillin-resistant isolates (oxacillin MICs >2 mg/L), 336 iso-lates (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.Retapamulininhibited663(99.9%)isolatesat 0.25 mg/L.Asinglemethicillin-resistant S.aureus isolate,alsowith high-level mupirocin resistance, required a retapamulin MIC of 2 mg/L, but its reduced susceptibility toretapamulinwasnotassociatedwithanymutationinribosomalproteinL3.Conclusions : Retapamulin demonstrated excellent activity in vitro against S. aureus isolates, irrespective oftheir level of resistance to other antibacterials. These results support the EUCAST epidemiological cut-offvalueforretapamulinof 0.5 mg/Lagainst S.aureus.Keywords: S. aureus, MRSA, mechanisms