Decreased ciprofloxacin susceptibility in Salmonella Typhi and Paratyphi infections in ill-returned travellers: the impact on clinical outcome and future treatment options

  • R.-J. Hassing
  • W. H. F. Goessens
  • D. J. Mevius
  • W. van Pelt
  • J. W. Mouton
  • A. Verbon
  • P. J. van Genderen
Article

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 (ƒAUC0–24/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 ƒAUC0–24/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 ƒAUC0–24/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 ƒAUC0–24/MIC ratio could be achieved by increasing the dose of ciprofloxacin or by the use of alternative fluoroquinolones.

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • R.-J. Hassing
    • 1
  • W. H. F. Goessens
    • 2
  • D. J. Mevius
    • 3
    • 4
  • W. van Pelt
    • 5
  • J. W. Mouton
    • 6
  • A. Verbon
    • 1
  • P. J. van Genderen
    • 7
  1. 1.Department of Internal Medicine and Infectious DiseasesErasmus Medical CentreRotterdamThe Netherlands
  2. 2.Department of Clinical Microbiology and Infectious DiseasesErasmus Medical CentreRotterdamThe Netherlands
  3. 3.Department of Infectious Diseases and Immunology, Faculty of Veterinary MedicineUtrecht UniversityUtrechtThe Netherlands
  4. 4.Central Veterinary Institute of Wageningen URLelystadThe Netherlands
  5. 5.National Institute for Public Health and the Environment (RIVM)BilthovenThe Netherlands
  6. 6.Department of Medical MicrobiologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  7. 7.Department of Internal MedicineHarbour Hospital and Institute for Tropical DiseasesRotterdamThe Netherlands

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