BACKGROUND: Traditional antibiotic dosing is not designed for patients at the intensive care unit, as the extreme pharmacokinetic behaviour of drugs in critically ill patients threatens the achievement of optimal antibiotic treatment outcomes. For severe infections, the pharmacodynamic target (PDT) of fAUC024/MIC 2.100 has been proposed. OBJECTIVE: In this study, we examine the PDT attainment of empirical dosing regimens of ciprofloxacin in critical ill patients and patient characteristics associated with the failure to achieve the PDT. DESIGN: A prospective observational PK/PD study was performed at the ICUs of Erasmus MC and Maasstad Hospital, Rotterdam. METHODS: Based on optimal sampling, five separate 5 mL samples were taken at various time points. Non-compartmental PK analysis was performed. The percentage PDT attainment was the primary endpoint. As a secondary endpoint, patient characteristics associated with the non-achievement of the PDT were evaluated using multivariate analysis. RESULTS: A total of 43 ICU patients receiving intravenous ciprofloxacin were included in this study. The median age was 66 years, APACHE II score was 22 and creatinine clearance rate was 58 mL/min. The median/AUC024 and Cmax were 29.9 mg.h/L and 3.0 mg/L, respectively. The proportion of patients achieving the PDT was 16.3%. Using multivariate analysis, an increase of the body mass index, creatinine clearance rate and albumin were found to be predictive of a decreased fAUC0-24/MIC ratio. CONCLUSION: An empirical approach of ciprofloxacin dosing results in poor target attainment in the majority of the ICU patients. At present, TDM of ciprofloxacin is not used as a routine intervention. We believe that should be changed, because of the high variability in PK parameters in critically ill patients.

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Persistent URL hdl.handle.net/1765/109194
Journal Pharmaceutisch Weekblad
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Abdulla, A, Hunfeld, N.G.M, Dijkstra, A, Duran, S. (S.), Gommers, D.A.M.P.J, Mouton, J.W, … Koch, B.C.P. (2018). A majority of the ICU patients treated with ciprofloxacin does not achieve the pharmacodynamic target Meerderheid van de intensivecarepatiënten behandeld met ciprofloxacine bereikt de farmacodynamische streefwaarde niet. Pharmaceutisch Weekblad, 153(23), 28–33. Retrieved from http://hdl.handle.net/1765/109194