Abstract

Aim: The standard dosage recommendations for β-lactam antibiotics can result in very low drug levels in intensive care (IC) patients and burn patients in the absence of renal dysfunction. We studied the pharmacokinetic parameters and serum concentrations of ceftazidime (CF) and cefepime (CE) in burn patients and analyzed the modifications according to clinical and biological parameters and in particular age and creatinine clearance. Material and methods: Two pharmacokinetic studies were carried out with daily doses of 1 g × 6 for CF (n = 17) and 2 g × 3 for CE (n = 13). Creatinine clearance (CLCR) was both estimated and measured. Blood was sampled at steady state after an initial and a subsequent antibiotic dose. Cmax (maximal) and Cmin (minimal) concentrations were measured by HPLC. The influence of clinical and biological data was analyzed using ANOVA, ANCOVA and stepwise multiple linear regression. Results: The ratio of Cmin to the low MIC break point (4 mg/l) was lower than 4 in 52% of subjects receiving CF and in 80% of subjects receiving CE. The Cmin of CF was correlated with measured CLCR and was higher in mechanically ventilated patients than in non-ventilated patients. The clearance of CF was correlated with age. The Cmin of CE was correlated with age and drug clearance with measured CLCR. Therefore dosage adjustment of these drugs in burn patients needs to take into account age, measured creatinine clearance and the danger of low concentrations occurring when the creatinine clearance is greater than 120 ml.min–1. Conclusion: In burn patients, the pharmacokinetic disposition of CF and CE was much more variable than in healthy subjects. Age and CLCR were predictors of the disposition of these antibiotics. Shortening the dosage interval or using continuous infusions will prevent low serum levels and keep trough levels above the MIC for longer periods of time. In view of the lack of a bedside measurement technique for ceftazidime and cefepime levels, we suggest a more frequent use of measured CLCR in order to attain efficacious clinical concentrations.

Author Details

Authors

• J.M. Conil
• B. Georges
• M. Lavit
• T. Seguin
• I. Tack
• K. Samii
• G. Chabanon
• G. Houin
• S. Saivin

Departments

• ¹ Service d’Anesthésie-Réanimation, Hôpital de Rangueil, Toulouse,
• ² Laboratoire de Pharmacocinétique et Toxicologie Clinique, Institut Fédératif de Biologie, Toulouse,
• ³ Laboratoire de Cinétique des Xénobiotiques, UMR
• ¹ 
• ⁸ 
• ¹  Physiopathologie et Toxicologie Expérimentale (UPTE INRA-ENVT), Faculté des Sciences Pharmaceutiques, Toulouse,
• ⁴ Laboratoire d’Explorations Fonctionnelles Physiologiques, Hôpital de Rangueil, Toulouse, and
• ⁵ Laboratoire de Bactériologie-Hygiène, Institut Fédératif de Biologie, Toulouse, France

Address

Dr. S. Saivin, Laboratoire de Pharmacocinétique et Toxicologie Clinique, Institut Fédératif de Biologie, 330 Avenue de Grande Bretagne TSA 40031, 31059 Toulouse Cedex 9, France
Email: [email protected]

Citation