Drug Design, Development and Therapy (Nov 2024)
Population Pharmacokinetic/Pharmacodynamic Study of Linezolid in Hospital-Acquired Pneumonia Patients with Renal Insufficiency
Abstract
Jin-hui Xu,1,* Xiang-long Chen,1,* Qian Zhang,1,* Zhiwei Zhuang,2 Yun-long Yuan,3 Lu-fen Duan,1 Lu Shi,1 Chenqi Zhu,1 Jing-Jing Li,1 Jian Lu,4 Yan-xia Yu,1 Lian Tang1,5 1Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 2Emergency Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 3Medical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 4Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 5Gusu School, Nanjing Medical University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian Tang; Yan-xia Yu, Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, No. 26 Daoqian Street, Gusu District, Suzhou, 215002, People’s Republic of China, Tel +86 512 6236 2325, Email [email protected]; [email protected]: The optimal treatment strategy in patients with hospital-acquired pneumonia (HAP) due to Gram-positive bacteria and renal insufficiency remains challenging. The objective of this study was to compare the outcomes of linezolid versus teicoplanin in HAP patients with renal insufficiency and to explore optimal dosage strategy for linezolid.Methods: The retrospective study enrolled adult patients treated with intravenous linezolid or teicoplanin at Suzhou Municipal Hospital between July 2018 and August 2023. For the comparative pharmacodynamic study, effectiveness, safety and target attainment of trough concentration (Cmin) for teicoplanin versus linezolid treatment in HAP patients with document Gram-positive bacteria and renal insufficiency were compared. For the population pharmacokinetics (PPK) analyses, linezolid concentrations collected exclusively from HAP patients with renal insufficiency were used and the optimal dosage strategy was investigated using Monte Carlo simulations.Results: Linezolid-treated patients had a higher bacterial eradication rate than teicoplanin-treated patients (88.5% vs 63.4%, P < 0.001). A higher proportion of patients in the linezolid group experienced at least one adverse reaction (42.0% vs 25.0%, P = 0.025). Significantly more supratherapeutic Cmin, less therapeutic Cmin were achieved in the linezolid group (adjusted P < 0.05). A total of 207 linezolid concentrations from 166 patients with renal insufficiency were available for the PPK analysis. Age and creatinine clearance (CrCL) were identified as significant covariates that influenced clearance. Simulations show that 300 mg q12h provide the optimal exposure in patients with a CrCL of 60 or 45 mL/min, and 200 mg q12h was recommended for patients with a CrCL of 30 or 15 mL/min.Conclusion: Linezolid-treated patients with HAP and renal insufficiency had higher bacterial eradication rates, supratherapeutic exposure and adverse reactions than teicoplanin-treated patients. Linezolid dose reduction in patients with renal insufficiency improved the probability of achieving optimal exposure.Keywords: linezolid, population pharmacokinetic, pharmacodynamic, renal insufficiency, hospital-acquired pneumonia
