This contemporary study showed that acquired fusidic acid resistance genes were prevalent among fusidic acid-non-susceptible European staphylococcal isolates.

Among 4,167 Staphylococcus aureus and 790 coagulase-negative Staphylococcus (CoNS; not S. saprophyticus) isolates collected consecutively from North American and Australian hospitals, only 87 (1.7% overall) isolates displayed a fusidic acid (FA; also known as CEM-102) MIC of >2 g/ml (FA resistance). These strains were further evaluated with a multiplex PCR to amplify the acquired resistance genes fusB, fusC, and fusD. Mutations in fusA and fusE were evaluated in all isolates showing an absence of acquired resistance genes and/or showing FA MIC values of >64 g/ml. S. aureus resistance rates were very low in the United States (0.3%) and were higher in Canada and Australia (7.0% for both countries). Among CoNS isolates, FA resistance rates were significantly more elevated than that for S. aureus (7.2 to 20.0%; the highest rates were in Canada). All 52 (41 CoNS) FA-resistant isolates from the United States showed FA MIC results of <64 g/ml, and 7 of 11 S. aureus isolates carried fusC. CoNS strains from the United States carried fusB or fusC. In Canada, fusB and fusC occurrences were similar among S. aureus and CoNS isolates, and modestly elevated FA MIC values were observed (all MIC results were <32 g/ml). Isolates from Australia showed MIC values ranging from 2 to 32 g/ml, and S. aureus isolates were predominantly fusC positive. fusA mutations were detected in only three S. aureus isolates, conferring FA MIC values of 2 to 8 g/ml. Target mutations have been considered the primary FA resistance mechanism among Staphylococcus spp.; however, acquired resistance genes appear to have a dominant role in resistance against this older antimicrobial agent. In summary, this study shows that acquired genes are highly prevalent among FA-resistant strains (>90%) in three nations with distinct or absence (United States) of fusidic acid clinical use.

Background: Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gram-positive bacteria currently used for the treatment of complicated skin and skin structure infections and bacteremia, including right sided endocarditis. We evaluated the in vitro activity of this compound and selected comparator agents tested against clinical strains of staphylococci and enterococci collected in European medical centers in 2005.

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With few differences detected among strains from various geographic regions, the first PDFI class agent to enter clinical development has consistently demonstrated a broad spectrum of activity against commonly isolated pathogens associated with uncomplicated respiratory and cutaneous infections. These compounds represent a significant therapeutic advance owing to their novel mechanism of action and antibacterial spectrum, including activity against resistant organisms, should pharmacokinetic and pharmacodynamic parameters support their continued development. Given the detection of a pre-existing PDFI-resistant isolate of S. aureus as demonstrated here, surveillance for resistance among the PDFI-targeted pathogens following introduction of this class of agent into clinical usage will be an important component of future studies.