Mutation frequencies for resistance to fusidic acid and rifampicin in Staphylococcus aureus

• Published in: Journal of antimicrobial chemotherapy Vol. 47; no. 5; pp. 647 - 650
• Main Authors: O'Neill, Alex J., Cove, Jonathan H., Chopra, Ian
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-05-2001; Oxford Publishing Limited (England)
• Subjects: Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Drug Resistance, Microbial - genetics; Drug Resistance, Multiple - genetics; Fusidic Acid - pharmacology; Gene Frequency; Humans; Medical sciences; Microbial Sensitivity Tests; Mutation; Pharmacology. Drug treatments; Rifampin - pharmacology; Staphylococcus aureus - drug effects; Staphylococcus aureus - genetics; Drug combination; Microorganism growth; Fusidic acid; In vitro; Resistance; Antibiotic; Rifampicin; Bacteria; Micrococcales; Micrococcaceae; Antituberculous agent; Drug interaction; Mutation; Antibacterial agent; Staphylococcus aureus
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/47.5.647

Frequencies at which mutants resistant to fusidic acid and/or rifampicin arose in vitro were determined in Staphylococcus aureus strains including methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-intermediate resistant S. aureus (VISA) and hetero-VISA. The concentrations of fusidic acid (30 and 15 mg/L) and rifampicin (16 and 1 mg/L) used for selection were equal to the expected maximum and minimum serum concentrations after an oral regimen of rifampicin 900 mg od, together with fusidic acid 500 mg tds. Resistant mutants arose at a frequency of around 10−8 for selections with rifampicin, but were undetectable (frequency <10−11) for selections with fusidic acid. Mutants were not recovered (frequency <10−11) after selections in the presence of both fusidic acid and rifampicin at 30/16 and 15/1 mg/L. Our results suggest that these antibiotics, when used in combination, could have a wider role in the management of staphylococcal infections.