Defining optimal dosing of ciprofloxacin in patients with septic shock

The Journal of Antimicrobial Chemotherapy
Jason A RobertsFredrik Sjövall

Abstract

Patients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics. To describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients. 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. 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 n...Continue Reading

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Apr 29, 2014·The Lancet Infectious Diseases·Jason A RobertsUNKNOWN International Society of Anti-Infective Pharmacology and the Pharmacokinetics and Pharmacodynamics Study Group of the Europe
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Sep 30, 2017·The Journal of Antimicrobial Chemotherapy·Fredrik SjövallJason A Roberts

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