| Title | Ciprofloxacin Dosage and Emergence of Resistance in Human Commensal Bacteria. | | Author(s) | Fantin B, Duval X, Massias L, Alavoine L, Chau F, Retout S, Andremont A, Mentré F | | Institution | Université Paris Diderot, 2EA3964, "Emergence de la résistance bactérienne in vivo," Université Paris Diderot, 3AP-HP Hôpital Beaujon, 4AP-HP Hôpital Bichat, 5INSERM CIC 007, 6INSERM UMR 738, 7Laboratoire de Toxicologie et Pharmacocinétique, Service de Pharmacie, and 8CNR "Résistance dans les flores commensales," AP-HP Hôpital Bichat, Paris, France. | | Source | J Infect Dis 2009 Aug 1; 200(3):390-398. | | Abstract | Background. Although optimization of the fluoroquinolone dosage increases the efficacy of this class of drugs against bacterial infections, its impact on the emergence of resistance in commensal bacteria is unknown. Methods. Six different 14-day dosages of oral ciprofloxacin were randomly assigned to 48 healthy volunteers. Individual pharmacokinetic and pharmacodynamic parameters combining antibiotic exposure in plasma, saliva, and stool specimens and ciprofloxacin minimum inhibitory concentrations (MICs) and mutant prevention concentrations against viridans group streptococci in the pharyngeal flora and Escherichia coli in the fecal flora were estimated. Their links with the emergence of resistance to nalidixic acid or ciprofloxacin in the fecal flora and to levofloxacin in the pharyngeal flora 7, 14, or 42 days after ciprofloxacin initiation were investigated.
Results. Resistance emerged in the fecal and pharyngeal flora of 25% and 33% of the subjects, respectively, mainly when local concentrations of ciprofloxacin were less than the MIC. No variable that integrated pharmacokinetic data and pharmacodynamic parameters was found to differ significantly between the subjects in whom resistance emerged and those in whom it did not. Probabilities of the emergence of resistance were not significantly different across the different antibiotic dosages.
Conclusions. Selection of resistant commensals during ciprofloxacin therapy is a frequent ecological side effect that is not preventable by dosage optimization. Trial registration. Clinical Trials.gov identifier: NCT00190151 . | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19563257 |
|
