{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["89(2)"],"submitter":["Roelofsen EE"],"pubmed_abstract":["<h4>Aims</h4>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.<h4>Methods</h4>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 NONMEM (v7.4.2). The percentage of patients reaching 100% fT>MIC<sub>ECOFF</sub> was used to compare different dosage regimens for Enterobacterales and S. aureus.<h4>Results</h4>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<sup>-1</sup> 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<sup>-1</sup> for S. aureus resulted in a minimum of 99% PTA.<h4>Conclusion</h4>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<sup>-1</sup> was adequate for all combinations of eGFR and albumin concentration. For S. aureus CI of 6 g 24 h<sup>-1</sup> would be preferred if eGFR and albumin concentration exceed 80 mL min<sup>-1</sup> and 40 g L<sup>-1</sup> respectively."],"journal":["British journal of clinical pharmacology"],"pagination":["705-713"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10087439"],"repository":["biostudies-literature"],"pubmed_title":["Dose optimization of cefotaxime as pre-emptive treatment in critically ill adult patients: A population pharmacokinetic study."],"pmcid":["PMC10087439"],"pubmed_authors":["Muller AE","Endeman H","de Winter BCM","Dijkstra A","Hunfeld NGM","Roelofsen EE","Gommers D","Koch BCP","Abdulla A"],"additional_accession":[]},"is_claimable":false,"name":"Dose optimization of cefotaxime as pre-emptive treatment in critically ill adult patients: A population pharmacokinetic study.","description":"<h4>Aims</h4>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.<h4>Methods</h4>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 NONMEM (v7.4.2). The percentage of patients reaching 100% fT>MIC<sub>ECOFF</sub> was used to compare different dosage regimens for Enterobacterales and S. aureus.<h4>Results</h4>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<sup>-1</sup> 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<sup>-1</sup> for S. aureus resulted in a minimum of 99% PTA.<h4>Conclusion</h4>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<sup>-1</sup> was adequate for all combinations of eGFR and albumin concentration. For S. aureus CI of 6 g 24 h<sup>-1</sup> would be preferred if eGFR and albumin concentration exceed 80 mL min<sup>-1</sup> and 40 g L<sup>-1</sup> respectively.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2024-11-12T00:21:02.341Z","creation":"2024-11-12T00:21:02.341Z"},"accession":"S-EPMC10087439","cross_references":{"pubmed":["35942921"],"doi":["10.1111/bcp.15487"]}}