Resistance to Ciprofloxacin in Epidemic and Sporadic Isolates of Methicillin-Resistant Staphylococcus aureus

The types of topoisomerase alterations in genomically diverse epidemic and sporadic strains of methicillin-and fluoroquinolone-resistant Staphylococcus aureus isolated from European hospitals between 1984 and 1994 were characterized. Convergent dual mutations in gyrA (codon 83, 84, or 88) and grlA (codon 79 and/or 80) were found in all strains exhibiting high-level resistance to ciprofloxacin (MIC, 16 to>128 mg/ml). In some epidemic strains, the resistant phenotype and genotype appeared in the 1990s and persisted thereafter. The emergence and rapid dissemination of fluoroquinolone (FQ) resistance in Staphylococcus aureus, especially among methicillin-resistant strains (MRSA) (11), has severely limited the therapeutic usefulness of these antimicrobial agents in the treatment of staphylococcal infections. Among the mecha-nisms of FQ resistance found in S. aureus, alterations of amino acids in the quinolone resistance determinant region (QRDR) of the GyrA subunit and, less commonly, of the GyrB subunit of DNA gyrase are found (5, 6, 13). Mutations in the GrlA subunit of DNA topoisomerase IV are also associated with F