Defining optimal dosing of ciprofloxacin in patients with septic shock

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BACKGROUND: Patients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics. OBJECTIVES: To describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients. METHODS: Adult patients with septic shock treated with ciprofloxacin were eligible for inclusion. Concentrations were measured by HPLC-MS/MS. Population pharmacokinetic modelling was performed with Monte Carlo simulations then used to define dosing regimens that optimize the PTA of an AUC/MIC ratio >125 for different MICs and fractional target attainment (FTA) of empirical and targeted therapy against Pseudomonas aeruginosa. RESULTS: We included 48 patients with median Simplified Acute Physiology Score (SAPS) II of 49 and 90 day mortality of 33%. Ciprofloxacin pharmacokinetics was best described by a two-compartment linear model including CLCR and body weight as covariates on CL and central volume respectively. With a dose of 400 mg q8h and CLCR of 80 mL/min, >95% PTA was achieved for bacteria with MICs ≤0.25 mg/L. For empirical treatment of P. aeruginosa, 600 mg q8h only reached a maximum of 68% FTA. For directed therapy against P. aeruginosa, a dose of 600 mg q8h was needed to achieve sufficient AUC/MIC ratios. CONCLUSIONS: In patients with septic shock, standard ciprofloxacin dosing achieved concentrations to successfully treat bacteria with MICs ≤0.25 mg/L and then only in patients with normal or reduced CLCR. To cover pathogens with higher MICs or in patients with augmented renal CL, doses may have to be increased.


  • Jason A. Roberts
  • Abdulaziz S. Alobaid
  • Steven C. Wallis
  • Anders Perner
  • Jeffrey Lipman
  • Fredrik Sjövall
Enheter & grupper
Externa organisationer
  • Royal Brisbane and Women's Hospital
  • University of Queensland
  • University of Copenhagen
  • Copenhagen University Hospital
  • Queensland University of Technology
  • Skåne University Hospital

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Gastroenterologi
Sidor (från-till)1662-1669
Antal sidor8
TidskriftThe Journal of antimicrobial chemotherapy
Utgåva nummer6
StatusPublished - 2019
Peer review utfördJa