Therapeutic Monitoring of Polymyxin B in Critically Ill Patients with Carbapenem-Resistant Organisms: Evaluation Based on Steady-State Trough and Peak Concentrations

Jun Yang,1,* Yunpei Zhao,1,* Linli Xie,1,* Yu Gan,1 Mingjie Yu,2 Ge Yang,1 Yongchuan Chen1 1Department of Pharmacy, The First Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China; 2Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongchuan Chen, Department of Pharmacy, the First Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China, Email zwmcyc@tmmu.edu.cnObjective: In critically ill patients with carbapenem-resistant organisms (CRO) infections, optimizing polymyxin B (PMB) exposure is crucial for survival. This prospective single-center study was conducted to assess the factors influencing the steady-state trough (Ctrough,ss) and peak concentrations (Cpeak,ss) of PMB, as well as the relationship between the steady-state 24-hour area under the concentration-time curve (AUCss,24h) of PMB, estimated from Ctrough,ss and Cpeak,ss and clinical efficacy.Methods: Plasma PMB concentrations were measured using liquid chromatography-tandem mass spectrometry. The first-order elimination kinetic equation was used to compute AUCss,24h based on Ctrough,ss and Cpeak,ss with the therapeutic window of PMB defined as AUCss,24h ranging from 50 to 100 mg·h·L− 1. Clinical effectiveness was defined as a composite of symptom improvement, inflammatory response reduction and stable oxygenation.Results: A total of 140 critically ill patients were enrolled, yielding 155 paired measurements for Ctrough,ss and Cpeak,ss from which 155 AUCss,24h values were calculated. PMB therapy was efficacious in 52.14% of cases, with 42.58% (66/155) having an AUCss of 50– 100 mg·h·L− 1 within 24h. Creatinine clearance (CrCL) and sepsis are both linked to low Ctrough,ss levels. Maintenance dose and haemoglobin (HGB) had positive relationships with Cpeak,ss but sepsis and APACHE II scores were negatively correlated. Higher AUCss,24h and maintenance of AUCss,24h within the therapeutic window were identified as favourable factors for clinical efficacy. However, advanced age, elevated blood urea nitrogen (BUN) and alkaline phosphatase (ALP) levels, and sepsis were risk factors.Conclusion: The PMB AUCss,24h estimated from Ctrough,ss and Cpeak,ss was closely correlated with clinical efficacy. The two-point sampling strategy based on steady-state trough and peak concentrations is applicable for therapeutic monitoring of PMB in critically ill patients.Keywords: polymyxin B, critical illness, steady-state concentration, carbapenem-resistant organisms, therapeutic monitoring