Intermittent administration of ceftazidime to burns patients: influence of glomerular filtration
Conil, J.M.; Georges, B.; Fourcade, O.; Seguin, T.; Houin, G.; Saivin, S.
International Journal of Clinical Pharmacology and Therapeutics 45(3): 133-142
2007
ISSN/ISBN: 0946-1965 PMID: 17416108 Document Number: 607840
Objective: The pharmacokinetics of ceftazidime, the antibiotic of choice for treating acute P. aeruginosa infections, may be modified in bums patients. The aim of this study was to identify the factors causing variations in the serum antibiotic concentrations in bums patients. Methods: 30 patients with serious bums were randomly divided into two groups. Group 1 received a dose of ceftazidime of 2 x 3 g/24 hours. The second group received the same dose but divided into 6 administrations. Blood samples were taken at 24 (M1) and 48 hours (M2) after the start of treatment and the peak and trough serum concentrations of ceftazidime measured by HPLC. Depending on the results, frequency and/or dose was modified to obtain trough concentrations (C-min) equal to 16 mg/l, i.e. 4 times the MIC. Either the same dose was maintained, but mostly divided up, or it was increased to I g x 8 administrations or it was decreased to 1 g x 4 or 1 g x 3. The serum concentrations of ceftazidime obtained were analyzed taking into account the characteristics of the bums patients (multivariate correlation). Results: From the first sample (M 1) Cmin was lower than the target concentration in 50% of the patients in Group 1 and 20% in Group 2. The modification of the dosing regimen put into place after the first analysis, led to the patients being further divided into four groups before the second blood sampling. Finally, 5 patients ended up in Group 1. In all patients and for all administration times a negative correlation was found between C-min and the creatinine clearance, calculated by using Cockcroft's formula. Conclusion: This study highlights the peculiarities of ceftazidime pharmacokinetics seen in bums patients with high interindividual variability. Based on C-min monitoring and a predefined therapeutic range, dose adjustment was often required. Ceftazidime clearance is correlated with creatinine clearance (Cockcroft's formula), suggesting that this parameter could be used for a priori or a posteriori dose individualization. To respect the summary of the product characteristics (SPC) and reduce the variability in trough concentrations, the dose should be fractionated (1 g x 6) over a 24 hour period or even given as a continuous infusion. Trough concentrations must be evaluated to adapt the dosage regimen to attain target concentrations of 4 x the MIC.