Journal of Antimicrobial Chemotherapy, Vol 40, 269-273, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
RJ Young, J Lipman, T Gin, CD Gomersall, GM Joynt and TE Oh
Ceftazidime is frequently used in critically ill patients, particularly for
the treatment of Pseudomonas aeruginosa infections. The recommended dosing
regimen is based on pharmacokinetic data obtained in healthy volunteers and
may not be appropriate in the critically ill. We administered ceftazidime
in the maximum recommended dose (2 g i.v. every 8 h) to ten critically ill
patients with normal plasma creatinine. Eighteen arterial blood samples
were taken from each patient over the first 8 h for measurement of
ceftazidime concentrations and subsequent compartmental pharmacokinetic
analysis. An additional trough sample was taken from each patient on day 3.
Although mean pharmacokinetic variables did not differ from previously
reported data in normal volunteers there was wide variability in plasma
drug concentrations. Three of our patients had plasma ceftazidime
concentrations less than the MIC for P. aeruginosa (8 mg/L) and nine had
concentrations less than 5 x MIC, which has been recommended to ensure
efficacy. On day 3 trough ceftazidime concentrations were less than the MIC
in four out of the seven patients in whom measurements were made and less
than 5 x MIC in the remaining three. There was no clinical predictor of
which patients would have low plasma concentrations. Our results show that
plasma concentrations of ceftazidime are very variable when the recommended
intermittent bolus dosing regimen is used and may result in inadequate
plasma concentrations of drug in critical infections. This may result in
treatment failure and the emergence of antibiotic resistance. A loading
dose followed by continuous infusion should overcome these problems but
this awaits in-vivo evaluation.
ORIGINAL ARTICLES
Intermittent bolus dosing of ceftazidime in critically ill patients
Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories.
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