Bacterial resistance to the quinolone antimicrobial agents

Bacterial resistance to the newer quinolones occurs less frequently than to the older analogue nalidixic acid. Single-step mutations conferring greater than eightfold increases in minimal inhibitory concentration occur at frequencies of less than 10(-10) for many bacterial species and at 10(-8) for Pseudomonas aeruginosa. Passage on increasing concentrations of quinolones, however, results in highly resistant strains of many species. Chromosomal mutations have been shown to produce two mechanisms of resistance, alterations in the A subunit of the target enzyme, DNA gyrase, and decreased drug accumulation associated with altered porin outer membrane proteins and pleiotropic resistance. For some mutants reduced accumulation appears to depend on active quinolone efflux across the inner membrane. Resistance developing during quinolone therapy of infections has been infrequent to date and reported most often with P. aeruginosa and Staphylococcus aureus, and at sites with poor quinolone penetration or foreign bodies. Resistance should be monitored, and the means for limiting its development studied.