Population Pharmacokinetic/Pharmacodynamic Study of Linezolid in Hospital-Acquired Pneumonia Patients with Renal Insufficiency

Drug Des Devel Ther. 2024 Nov 8:18:5073-5086. doi: 10.2147/DDDT.S474470. eCollection 2024.

Abstract

Purpose: 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: hospital-acquired pneumonia; linezolid; pharmacodynamic; population pharmacokinetic; renal insufficiency.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / adverse effects
  • Anti-Bacterial Agents* / pharmacokinetics
  • Anti-Bacterial Agents* / pharmacology
  • Female
  • Healthcare-Associated Pneumonia* / drug therapy
  • Healthcare-Associated Pneumonia* / microbiology
  • Humans
  • Linezolid* / administration & dosage
  • Linezolid* / adverse effects
  • Linezolid* / pharmacokinetics
  • Linezolid* / therapeutic use
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Renal Insufficiency* / drug therapy
  • Renal Insufficiency* / metabolism
  • Retrospective Studies
  • Teicoplanin / administration & dosage
  • Teicoplanin / adverse effects
  • Teicoplanin / pharmacokinetics
  • Teicoplanin / pharmacology
  • Teicoplanin / therapeutic use

Substances

  • Linezolid
  • Anti-Bacterial Agents
  • Teicoplanin

Grants and funding

This work was supported by the Suzhou Science and Technology Project (SKJYD2021170, SKJYD2021171, SKJYD2021172); Jiangsu Pharmaceutical Association Hospital Pharmacy Research Project (H202109, A202228, SY202304-3, H202334); Jiangsu Research Hospital Association for Precision Medication (JY202203, JY202204, JY202212); Suzhou Pharmaceutical Association Hospital Pharmacy Research Project (Syhky202313, Syhky202312); Suzhou Special Technical Project for Diagnosis and Treatment of Key Clinical Diseases (LCZX202112); Gusu Talent Program (GSWS2022069) and Collaborative Innovation Project of Gusu School of Nanjing Medical University (GSKY20240207); to Drug Safety Research Project by Adverse Drug Reactions Journal (ADR2024MS21); Clinical Research Fund of Nanjing Medical University (2024KF0237); China Medical and Health Development Foundation (202427).