Case Report: Therapeutic Drug Monitoring of Polymyxin B During Continuous Renal Replacement Therapy in Two Pediatric Patients: Do Not Underestimate Extracorporeal Clearance

• Published in: Frontiers in pharmacology Vol. 13; p. 822981
• Main Authors: Xu, Caifang, Liu, Xiaofen, Cui, Yun, Huang, Xiaolan, Wang, Yu, Fan, Yaxin, Wu, Hailan, Li, Xin, Guo, Beining, Zhang, Jing, Zhang, Yucai
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 24-03-2022
• Subjects: children; CRRT; pharmacokinetic; Pharmacology; polymyxin B; therapeutic drug monitoring; pharmacokinetic; children; polymyxin B; CRRT; therapeutic drug monitoring
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2022.822981

Polymyxin B has become the last choice for patient with carbapenem-resistant bacterial infection. However, the optimal dosing of polymyxin B in critically ill children receiving continuous renal replacement therapy (CRRT) remains unclear.
Two cases of critically ill pediatric patients (7 years old) with acute kidney injury requiring continuous renal replacement (CRRT) received polymyxin B treatment due to carbapenem-resistant organism bloodstream infections. Therapeutic drug monitoring (TDM) of polymyxin B was carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS). The average steady-state plasma concentration (C
) of 2-4 mg/L was set as the target level. Initial polymyxin B dose was 1 mg/kg every 12 h, and the C
at 4-5th dosing were 1.76 and 1.06 mg/L for patient 1 and patient 2, respectively. TDM-guided polymyxin B dose was escalated to 2 mg/kg every 12 h for both patients, resulting in the C
of 2.60 and 1.73 mg/L, and the infection was controlled subsequently. C
of polymyxin B with the same dosing regimens and infusion length were different during CRRT and after termination of CRRT for both patients (2.60 mg/L vs. 4.94 mg/L with 2 mg/kg every 12 h in 2 h infusion for patient 1; and 1.73 mg/L vs. 3.53 mg/L with 2 mg/kg every 12 h in 2 h infusion for patient 2). The estimation of drug exposure (estimated by AUC
at the same dose) during CRRT and cessation of CRRT showed that 45% and 51% of polymyxin B was cleared during CRRT.
Our study showed high clearance of polymyxin B through CRRT, and supplanted dosing of polymyxin B is necessary in pediatric patients undergoing CRRT.