Detection of fusidic acid resistance in Staphylococcus aureus and analysis of molecular characteristics

Abstract

Objective To investigate fusidic acid resistance in Staphylococcus aureus (S.aureus) strains and to analyze their molecular characteristics. Methods A total of 1 333 strains of S. aureus isolated in the First Affiliated Hospital of Wenzhou Medical University from October 2013 to March 2016 were collected. Fusidic acid resistance in these strains was detected by K-B method. Minimum inhibitory concentrations (MIC) of fusidic acid were measured by agar dilution method. Resistance genes of fusB, fusC and fusD and S. aureus A protein-coding gene (spa) were detected by PCR. Strains that did not carry fusB, fusC or fusD were detected for mutations in fusA by sequencing. Housekeeping genes were detected by PCR and analyzed by multilocus sequence typing (MLST). Results Among the 1 333 strains of S. aureus, 52 were resistant to fusidic acid, accounting for 3.90%. From 2013 to 2016, fusidic acid-resistant strains accounted for 5.3% (7/132), 3.5% (20/571), 4.1% (21/510) and 3.3% (4/120), respectively. The MIC values of fusidic acid against S. aureus were 2, 4, 8, 64 and >64 μg/ml, which inhibited the growth of 26.9% (14/52), 34.6% (18/52), 13.5% (7/52), 1.9% (1/52) and 23.1% (12/52) of strains, respectively. MLST revealed that there were 13 sequence types (STs), among which ST630 was the predominant type accounting for 50% (26/52), followed by ST5 accounting for 17.3% (9/52). There were 19 spa types, among which t4549 (11/52), t2460 (8/52), t377 (8/52) were the predominant types. Nine strains carried drug resistance genes accounting for 17.3% (9/52), including seven fusB-positive and two fusD-positive strains. No fusc-positive strains were detected. Mutations in fusA gene were detected in 11 strains (21.2%, 11/52) and the MIC values against them were all >64 μg/ml. The predominant type of the strains with fusA gene mutations was ST5-t2460. Conclusion Fusidic acid shows a good and relatively stable in vitro antibacterial activity against S. aureus. The mechanism of high resistance to fusidic acid is closely related to fusA gene mutation. Key words: Staphylococcus aureus; Fusidic acid; Resistance; MIC; Resistance gene; Genotyping