Bacterial resistance to quinolones: mechanisms and clinical importance

An overview of bacterial resistance to new quinolones is presented with a consideration of mechanisms, clinical importance, and approaches to suppression of the emergence of resistance. Single-step mutation to high-level resistance occurs at a frequency of less than or equal to 10(-10) for many bacterial species but can be readily selected by serial exposure of cells to increasing drug concentrations. Two mechanisms of resistance have been identified: alteration in the target enzyme DNA gyrase and decreased drug permeation. Emergence of resistance to clinically useful quinolones thus far has been uncommon. Superinfection has been documented but also has been uncommon. Emergence of resistance appears to occur more often with certain bacterial species, including Pseudomonas aeruginosa and Staphylococcus aureus. In the special setting of cystic fibrosis, patients with P. aeruginosa infections often respond favorably despite emergence of resistance. Methods to minimize the emergence of quinolone resistance should be evaluated in an effort to preserve the clinical utility of these drugs.