title: Decreased ciprofloxacin susceptibility in Salmonella Typhi and Paratyphi infections in ill-returned travellers: the impact on clinical outcome and future treatment options.
abstract: The emergence of decreased ciprofloxacin susceptibility (DCS) in Salmonella enterica serovar Typhi and serovar Paratyphi A, B or C limits treatment options. We studied the impact of DCS isolates on the fate of travellers returning with enteric fever and possible alternative treatment options. We evaluated the clinical features, susceptibility data and efficacy of empirical treatment in patients with positive blood cultures of a DCS isolate compared to patients infected with a ciprofloxacin-susceptible (CS) isolate in the period from January 2002 to August 2008. In addition, the pharmacokinetic and pharmacodynamic parameters of ciprofloxacin, levofloxacin and gatifloxacin were determined to assess if increasing the dose would result in adequate unbound fraction of the drug 24-h area under the concentration-time curve/minimum inhibitory concentration (ƒAUC(0-24)/MIC) ratio. Patients with DCS more often returned from the Indian subcontinent and had a longer fever clearance time and length of hospital stay compared to patients in whom the initial empirical therapy was adequate. The mean ƒAUC(0-24)/MIC was 41.3 ± 18.8 in the patients with DCS and 585.4 ± 219 in patients with a CS isolate. For DCS isolates, the mean ƒAUC0-24/MIC for levofloxacin was 60.5 ± 28.7 and for gatifloxacin, it was 97.9 ± 28.0. Increasing the dose to an adequate ƒAUC(0-24)/MIC ratio will lead to conceivably toxic drug levels in 50% of the patients treated with ciprofloxacin. Emerging DCS isolates has led to the failure of empirical treatment in ill-returned travellers. We demonstrated that, in some cases, an adequate ƒAUC(0-24)/MIC ratio could be achieved by increasing the dose of ciprofloxacin or by the use of alternative fluoroquinolones.
authors.affiliation: Department of Internal Medicine and Infectious Diseases, Erasmus Medical Centre, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands, r.hassing@erasmusmc.nl.
authors.forename: R-J
authors.initials: RJ
authors.lastname: Hassing
authors.forename: W H F
authors.initials: WH
authors.lastname: Goessens
authors.forename: D J
authors.initials: DJ
authors.lastname: Mevius
authors.forename: W
authors.initials: W
authors.lastname: van Pelt
authors.forename: J W
authors.initials: JW
authors.lastname: Mouton
authors.forename: A
authors.initials: A
authors.lastname: Verbon
authors.forename: P J
authors.initials: PJ
authors.lastname: van Genderen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001769:Blood / Q000382:microbiology; D002648:Child; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010284:Paratyphoid Fever / Q000382:microbiology; D012189:Retrospective Studies; D012482:Salmonella paratyphi A / Q000187:drug effects* / Q000302:isolation & purification; D012485:Salmonella typhi / Q000187:drug effects* / Q000302:isolation & purification; D014195:Travel; D016896:Treatment Outcome; D014435:Typhoid Fever / Q000382:microbiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin