Distribution of fusidic acid resistance determinants in methicillin-resistant Staphylococcus aureus.

The prevalence of resistance to fusidic acid in clinical isolates of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), has increased in the past 2 decades. However, there are limited data regarding the relative importance in this process of the different staphylococcal determinants that mediate resistance to fusidic acid. Furthermore, the roles played by clonal dissemination of fusidic acid-resistant strains versus horizontal transmission of fusidic acid resistance determinants have not been investigated in detail. To gain insight into both issues, we examined fusidic acid resistance in 1,639 MRSA isolates collected in Denmark between 2003 and 2005. Resistance to fusidic acid (MIC, >1 µg/ml) was exhibited by 291 (17.6%) isolates. For the majority of these isolates (∼87%), resistance was attributed to carriage of fusB or fusC, while the remainder harbored mutations in the gene (fusA) encoding the drug target (EF-G). The CC80-MRSA-IV clone carrying fusB accounted for ∼61% of the resistant isolates in this collection, while a single CC5 clone harboring fusC represented ∼12% of the resistant strains. These findings emphasize the importance of clonal dissemination of fusidic acid resistance within European MRSA strains. Nonetheless, the distribution of fusB and fusC across several genetic lineages, and their presence on multiple genetic elements, indicates that horizontal transmission of fusidic acid resistance genes has also played an important role in the increasing prevalence of fusidic acid resistance in MRSA.

High prevalence of resistance to fusidic acid in clinical isolates of Staphylococcus epidermidis.

OBJECTIVES: To determine the prevalence and mechanisms of resistance to fusidic acid in clinical isolates of Staphylococcus epidermidis. METHODS: MICs of fusidic acid were determined for S. epidermidis isolates collected from the Leeds General Infirmary and from around Europe. Fusidic acid-resistant isolates were probed for the presence of the horizontally acquired resistance determinants fusB and fusC by a novel multiplex PCR assay. Mutations in the gene encoding the drug target (fusA) were detected by PCR and DNA sequencing. Resistant isolates were subjected to typing using the repeat region of the aap gene. RESULTS: Of 50 S. epidermidis isolates screened, 23 (46%) exhibited resistance to fusidic acid. The most common resistance determinant was fusB, found in 18 of the 23 isolates. Of the remaining isolates, two harboured fusC and three carried an identical mutation in fusA, leading to the substitution L(461)K in the target protein, elongation factor G. Molecular typing showed that this collection of isolates was genetically diverse. CONCLUSIONS: This study suggests a high prevalence of resistance to fusidic acid in clinical isolates of S. epidermidis. As in Staphylococcus aureus, resistance to fusidic acid in S. epidermidis is commonly associated with the fusB determinant.

Genetic basis of resistance to fusidic acid in staphylococci.

Resistance to fusidic acid in Staphylococcus aureus often results from acquisition of the fusB determinant or from mutations in the gene (fusA) that encodes the drug target (elongation factor G). We now report further studies on the genetic basis of resistance to this antibiotic in the staphylococci. Two staphylococcal genes that encode proteins exhibiting ca. 45% identity with FusB conferred resistance to fusidic acid in S. aureus. One of these genes (designated fusC) was subsequently detected in all fusidic acid-resistant clinical strains of S. aureus tested that did not carry fusB or mutations in fusA, and in strains of S. intermedius. The other gene (designated fusD) is carried by S. saprophyticus, explaining the inherent resistance of this species to fusidic acid. Fusidic acid-resistant strains of S. lugdunensis harbored fusB. Thus, resistance to fusidic acid in clinical isolates of S. aureus and other staphylococcal species frequently results from expression of FusB-type proteins.