INTERMITTENT BOLUS DOSING OF CEFTAZIDIME IN CRITICALLY ILL PATIENTS

Ceftazidime is frequently used in critically ill patients, particularl y for the treatment of Pseudomonas aeruginosa infections. The recommen ded dosing regimen is based on pharmacokinetic data obtained in health y volunteers and may not be appropriate in the critically iii. We admi nistered ceftazidime in the maximum recommended dose (2 g iv every 8 h ) to ten critically ill patients with normal plasma creatinine. Eighte en arterial blood samples were taken from each patient over the first 8 h for measurement of ceftazidime concentrations and subsequent compa rtmental pharmacokinetic analysis. An additional trough sample was tak en from each patient on day 3. Although mean pharmacokinetic variables did not differ from previously reported data in normal volunteers the re was wide variability in plasma drug concentrations. Three of our pa tients had plasma ceftazidime concentrations less than the MIC for P. aeruginosa (8 mg/L) and nine had concentrations less than 5 x MIG, whi ch has been recommended to ensure efficacy. On day 3 trough ceftazidim e concentrations were less than the MIC in four out of the seven patie nts in whom measurements were made and less than 5 x MIC in the remain ing three. There was no clinical predictor of which patients would hav e low plasma concentrations. Our results show that plasma concentratio ns of ceftazidime are very variable when the recommended intermittent bolus dosing regimen is used and may result in inadequate plasma conce ntrations of drug in critical infections. This may result in treatment failure and the emergence of antibiotic resistance. A loading dose fo llowed by continuous infusion should overcome these problems but this awaits in-vivo evaluation.