Aims: To describe the pharmacokinetics (PK) of cefotaxime as pre-emptive treatment in critically ill adult patients, including covariates and to determine the probability of target attainment (PTA) of different dosage regimens for Enterobacterales and Staphylococcus aureus.
Methods: Five samples were drawn during 1 dosage interval in critically ill patients treated with cefotaxime 1 g q6h or q4h. PK parameters were estimated using NON-MEM (v7.4.2). The percentage of patients reaching 100% fT>MICECOFF was used to compare different dosage regimens for Enterobacterales and S. aureus.
Results: This study included 92 patients (437 samples). The best structural model was a 2-compartment model with a combined error, interindividual variability on clearance, central volume and intercompartmental clearance. Correlations between interindividual variability were included. Clearance increased with higher estimated glomerular filtration rate (eGFR; creatinine clearance) and albumin concentration. For Enterobacterales, 1 g q8h reached 95% PTA and continuous infusion (CI) of 4 g 24 h(-1) 100% PTA at the highest eGFR and albumin concentration. For S. aureus the predefined target of 95% PTA was not reached with higher eGFR and/or albumin concentrations. CI of 6 g 24 h(-1) for S. aureus resulted in a minimum of 99% PTA.
Conclusion: Cefotaxime PK in critically ill patients was best described by a 2-compartment model with eGFR and albumin concentration as covariates influencing clearance. For Enterobacterales 1 g q8h or CI of 4 g 24 h(-1) was adequate for all combinations of eGFR and albumin concentration. For S. aureus CI of 6 g 24 h(-1) would be preferred if eGFR and albumin concentration exceed 80 mL min(-1) and 40 g L-1 respectively.
Bibliographical noteFunding Information:
information The study was performed at the Erasmus MC and the Maasstad Hospital. The authors confirm that the Principal Investigators for this paper were Birgit Koch (Erasmus MC), Henrik Endeman (Erasmus MC) and Annemieke Dijkstra (Maasstad Hospital) and that they had direct clinical responsibility for patients.The authors are much obliged to Prof. Dr Johan W. Mouton for all his work. The authors would like to thank all the participants, the ICU teams, and the pharmacy laboratory of the Erasmus University Medical Center in Rotterdam. An abstract with part of the results has been presented at ECCMID and IATDMCT congress. The EXPAT study was supported by the Erasmus Medical Center; no specific funding was received.
An abstract with part of the results has been presented at ECCMID and IATDMCT congress. The EXPAT study was supported by the Erasmus Medical Center; no specific funding was received.
© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.