EMERGING RESISTANCE TO FLUOROQUINOLONES IN STAPHYLOCOCCI - AN ALERT

The use of fluoroquinolones as oral therapeutic agents for staphylococcal infections, problems with bacterial resistance, and approaches to suppression of resistance are discussed. Although they are particularly effective for treatment of gram-negative bacillary infections, quinolones, including ciprofloxacin and pefloxacin in limited experience, have been effective in treating staphylococcal infections. Clinical failures have occurred, however, in association with emergence of resistance or poor delivery of drug to the infected site. Recent surveys of drug susceptibility reveal substantial increases in resistance among methicillin-resistant and to a lesser extent methicillin-susceptible Staphylococcus aureus. Some strains were isolated from patients not receiving quinolone therapy. Resistance occurs by mutation in chromosomal genes, by mechanisms not yet defined, but probably involving either alteration of the target enzyme DNA gyrase or changes in drug accumulation, or both. Strategies to suppress emergence of fluoroquinolone resistance should be evaluated, including prudent drug use, use of combination drug therapy, and development of fluoroquinolone derivatives that have a higher therapeutic index and are less prone to select resistant organisms.