title: [Low-level resistance to fluoroquinolones conferred by efflux overproduction in Pseudomonas aeruginosa: clinical significance and routine detection].
abstract: The aim of this study was (i) to assess the impact of stable overproduction of efflux systems MexAB-OprM and MexXY-OprM on the bacteriostatic activities of fluoroquinolones in clinical Pseudomonas aeruginosa strains and (ii) to find a convenient test for screening isolates with a low level resistance to fluoroquinolones. The minimal inhibitory concentrations (MICs) of ciprofloxacin and levofloxacin were determined for clinical isolates of P. aeruginosa overexpressing MexAB-OprM or MexXY-OprM. Efflux pumps derepression was associated with a modest two- to fourfold increase in resistance to the tested fluoroquinolones. Clinical significance of low level resistance conferred by the efflux mechanism was evaluated with a Monte Carlo simulation with various fluoroquinolone regimens. With this model, low levels of resistance to ciprofloxacin (MIC > or =0.25 mg/L) or levofloxacin (MIC > or =1 mg/L) such as those due to overproduced MexAB-OprM or MexXY-OprM were predicted to result in poor clinical outcomes. Altogether these data strongly suggest that when derepressed MexAB-OprM or MexXY-OprM provides P. aeruginosa with a resistance that may be sufficient to impair the efficacy of single therapy with highly potent fluoroquinolones such as ciprofloxacin and levofloxacin. Routine detection of clinical strains that displayed low-level resistance to fluoroquinolones with a Mueller Hinton agar containing 0.20 mg/L of ciprofloxacin will help clinician in his therapeutical choice.
authors.affiliation: Laboratoire de bactériologie, CHU Jean-Minjoz, 1 boulevard Fleming, université de Franche-Comté, 25030 Besançon cedex, France. dhocquet@chu-besancon.fr
authors.forename: D
authors.initials: D
authors.lastname: Hocquet
authors.forename: I
authors.initials: I
authors.lastname: Patry
authors.forename: P
authors.initials: P
authors.lastname: Dupont
authors.forename: M
authors.initials: M
authors.lastname: Bize
authors.forename: K
authors.initials: K
authors.lastname: Jeannot
authors.forename: P
authors.initials: P
authors.lastname: Chavanet
authors.forename: P
authors.initials: P
authors.lastname: Plésiat
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000379:methods; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D012680:Sensitivity and Specificity
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones