OBJECTIVES
We sought to identify and characterise resistance to daptomycin amongst clinical-isolates of S.aureus referred to ARMRL over 69 weeks from the end of April 2007.
METHODS
MICs of daptomycin were determined by agar dilution (BSAC method) and re-confirmed if > 1 (= resistant; BSAC/EUCAST). Daptomycin-resistant isolates were characterised by phage and PFGE, and stored on agar slopes. Repeat patient-isolates were excluded unless of a different MIC of daptomycin or strain type. MICs of daptomycin were subsequently re-examined by controlled-paired E-tests at pH 7.4 and 7.8. The mprF gene of isolates with a daptomycin MIC ³4 was examined for known mutations.
RESULTS
Six non-repeat clinical-isolates of S. aureus with MICs of daptomycin > 1 were identified from mid Jan 2008, representing 1.2 % of submissions. Original MICs of daptomycin were: 2 (n=3), 4 (n=2) and 8 (n=1). All were resistant to oxacillin (MICs >16) and and characterised as healthcare associated MRSA. MICs of glycopeptides were 2-4 (breakpoint = 4). After storage, two isolates had reverted to sensitivity to daptomycin (MICs decreased from 8 and 2 to 0.125). Increasing the pH to 7.8 (controlled-pair tests) for the three stable daptomycin-resistant isolates produced small MIC reductions for two (from 1.5 to 0.5 & 4 to 3) whilst one was unaffected. No known mutations in the mprF gene were identified.
CONCLUSION
Resistance to daptomycin in S. aureus is rare and not necessarily stable. As an increased pH may influence non-susceptibility, and resistance was not associated with mprF mutations, several mechanisms may exist.