Population Pharmacokinetics of Total and Free Ceftriaxone in Critically Ill and Non-Critically Ill Hospitalised Adult Patients

Setiawan, Eko and Gonzalez, Alvaro and Wölky, Saskia A. and Cotta, Menino Osbert and Liu, Xin and Sosilya, Hernycane and Maresco-Pennisi, Diane and Novy, Emmanuel and Ordonez, Jenny and Lukas, Dwi Lily and Wallis, Steven C. and Xie, Jiao and Roberts, Jason A. and Abdul-Aziz, Mohd-Hafiz (2026) Population Pharmacokinetics of Total and Free Ceftriaxone in Critically Ill and Non-Critically Ill Hospitalised Adult Patients. International Journal of Antimicrobial Agents, 67 (8). p. 107817. ISSN 1872-7913 (In Press)

PDF Population Pharmacokinetics of Total and Free Ceftriaxone in Critically Ill and Non-Critically Ill Hospitalised Adult Patients.pdf Download (2MB)

Abstract

Objective: To characterise the population pharmacokinetics of total and free ceftriaxone in critically ill and non-critically ill Indonesian patients, define optimised dosing regimens against common hospital pathogens implicated in severe pneumonia and complicated urinary tract infections (UTI), and compare these findings with published data to support broader applicability. Method: This study recruited critically ill and non-critically ill adults receiving intravenous ceftriax- one. Serial plasma samples were collected over one dosing interval. Total and free ceftriaxone concen- trations were measured using a validated UHPLC-MS/MS method. Population pharmacokinetic analysis was performed using Monolix. Dosing simulations were performed to assess the probability of efficacy (100%fT > MIC for a given MIC) and toxicity risk (total trough concentration > 100 mg/L) on days 1 and 3 of therapy. Fractional target attainment was evaluated using EUCAST MIC distributions for common pathogens implicated in severe pneumonia and complicated UTI. Results: Fifty-three patients were recruited (median age, 57 years [IQR 39-65]; median eGFRCKD-EPI 67 mL/min/1.73 m2 [31.4-92.3]; 26 males; 42% ICU). A two-compartment model with complex protein binding best described the data with eGFRCKD-EPI as the primary determinant of clearance. Once-daily in- termittent infusion regimens (1 and 2 g every 24 h) failed to achieve optimal efficacy targets in patients with preserved or augmented renal function (eGFRCKD-EPI ≥60 mL/min/1.73 m2 ). Conclusion: A simplified renal function-stratified dosing strategy provided the best balance between safety and efficacy for empirical treatment; 1 g every 24 h for patients with eGFRCKD-EPI ≤60 mL/min/1.73 m2 and 1 g every 12 h for patients with eGFRCKD-EPI > 60 mL/min/1.73 m2 .

Item Type:	Article
Uncontrolled Keywords:	Cephalosporins; Dosing; Pharmacokinetics; Severe pneumonia
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Pharmacy > Department of Pharmacy
Depositing User:	BAMBANG SEPTIAWAN
Date Deposited:	17 Jun 2026 02:08
Last Modified:	17 Jun 2026 02:08
URI:	http://repository.ubaya.ac.id/id/eprint/50842

Actions (login required)

View Item