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Intermittent bolus dosing of ceftazidime in critically ill patients
1Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories.
Abstract:
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.
Insights
The standard ceftazidime dosing may lead to unpredictable drug levels in critically ill patients, potentially causing treatment failure and antibiotic resistance. Continuous infusion might offer a solution.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Ceftazidime is a vital antibiotic for treating Pseudomonas aeruginosa infections in critically ill patients.
- Current dosing recommendations are based on data from healthy individuals and may not be suitable for the critically ill.
- Variability in drug concentrations can impact treatment efficacy and contribute to resistance.
Purpose of the Study:
- To evaluate the pharmacokinetic variability of ceftazidime in critically ill patients.
- To determine if standard dosing achieves adequate drug concentrations for effective treatment of P. aeruginosa infections.
- To identify potential clinical predictors of suboptimal ceftazidime concentrations.
Main Methods:
- Ten critically ill patients with normal renal function received the maximum recommended dose of ceftazidime (2 g IV every 8 hours).
- Arterial blood samples were collected over 8 hours for pharmacokinetic analysis.
- Trough samples were obtained on day 3 to assess sustained drug levels.
Main Results:
- Significant variability in plasma ceftazidime concentrations was observed among patients.
- Three patients had concentrations below the minimum inhibitory concentration (MIC) for P. aeruginosa.
- Four out of seven patients had trough concentrations below the MIC on day 3.
Conclusions:
- The standard intermittent bolus dosing of ceftazidime results in highly variable and potentially inadequate plasma concentrations in critically ill patients.
- This variability may lead to treatment failure and the development of antibiotic resistance.
- Alternative dosing strategies, such as a loading dose followed by continuous infusion, warrant further investigation.