Empirical models for dosage optimization of four beta-lactams in critically ill septic patients based on therapeutic drug monitoring of amikacin.
OBJECTIVE
The study aims to develop empirical models able to predict the pharmacokinetics (PK) of four beta-lactams using the amikacin (AMK) therapeutic drug monitoring (TDM), in order to optimize their dosage regimens.


METHODS
69 critically ill septic patients were included. All received a first dose of AMK combined with piperacillin/tazobactam, ceftazidime, cefepime or meropenem. A multivariate analysis was performed to predict the beta-lactam PK using AMK PK parameters estimated from TDM and using pathophysiological variables.


RESULTS
An optimal prediction model was identified for each PK parameter of each beta-lactam. The best predictor of each model was one of the AMK PK parameters estimated from TDM. Other variables included colloid solution, renal and hepatic biomarkers, age and body weight.


CONCLUSIONS
PK of the four beta-lactams could be easily and rapidly predicted in critically ill septic patients using the AMK TDM. These predictions could improve the beta-lactam dosages in clinical practice.
Delattre
Isabelle K
IK
Unit of Clinical Biochemistry, Université Catholique de Louvain, Avenue Hippocrate, 10, B-1200 Brussels, Belgium.
Musuamba
Flora T
FT
Verbeeck
Roger K
RK
Dugernier
Thierry
T
Spapen
Herbert
H
Laterre
Pierre-François
PF
Wittebole
Xavier
X
Cumps
Jean
J
Taccone
Fabio S
FS
Vincent
Jean-Louis
JL
Jacobs
Frédérique
F
Wallemacq
Pierre E
PE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002138:Calibration; D016638:Critical Illness / Q000628:therapy*; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D036262:Empirical Research; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult; D047090:beta-Lactams / Q000008:administration & dosage*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000583:Amikacin