title: Bacterial resistance to fluoroquinolones.
abstract: Fluoroquinolones inhibit bacteria by interacting with the A subunit of DNA gyrase. Resistance to older agents such as nalidixic acid was due to mutations in the gyrA gene. Resistance to the new fluoroquinolones (e.g., norfloxacin, enoxacin, ofloxacin, pefloxacin, and ciprofloxacin) as a consequence of spontaneous single-step mutation occurs at a low frequency, less than 10(-9), and generally results in a 300-fold lower level of resistance than does the mutation to nalidixic acid resistance. High-level resistance to quinolones can be produced by serial exposure of bacteria to subinhibitory concentrations. Cross-resistance to all quinolones usually occurs. High-level resistance appears to be due to alterations in the A subunit of DNA gyrase and in a simultaneous alteration in permeability that probably is related to a loss of outer-membrane proteins. Organisms resistant to the new quinolones may also be resistant to other antibiotic classes, including beta-lactams. Clinical resistance to the new quinolones has been uncommon and has occurred most often among respiratory pathogens, particularly Pseudomonas aeruginosa from patients with cystic fibrosis and, less frequently, among strains of Serratia marcescens, P. aeruginosa, and Staphylococcus aureus from wound infections. Resistance of urinary or diarrheal isolates has been rare. So far, overall resistance of bacteria to quinolones has not emerged as a major problem, but--like resistance to all other antimicrobial classes--does occur in certain clinical settings.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York.
authors.forename: H C
authors.initials: HC
authors.lastname: Neu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D004352:Drug Resistance, Microbial; D005461:Fluorine / Q000494:pharmacology; D006801:Humans; D009154:Mutation; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011804:Quinolines; D005461:Fluorine