# Evaluation of the clinical efficacy, safety, and permeability in pulmonary epithelial lining fluid of contezolid, a novel oxazolidinone drug, in adult patients with pneumonia

## TL;DR

Contezolid, a new antibiotic, shows good effectiveness and safety in treating pneumonia by reaching high concentrations in lung fluid.

## Contribution

Demonstrates contezolid's strong pulmonary penetration and clinical efficacy in pneumonia patients.

## Key findings

- Contezolid achieved an 80% clinical cure rate and 71.4% bacterial clearance in pneumonia patients.
- The drug reached high concentrations in pulmonary epithelial lining fluid with an ELF-to-free plasma AUC ratio of 4.50.
- 800 mg twice daily of contezolid effectively met therapeutic targets for pathogens with MIC ≤4 mg/L.

## Abstract

Contezolid is a novel oxazolidinone antibiotic for the treatment of gram-positive bacteria, which are one of the most common pathogens of pneumonia. We conducted a prospective, single-center, open-label study to evaluate the clinical and microbiological efficacy, safety profile, and pulmonary epithelial lining fluid (ELF) penetration characteristics of contezolid in adult pneumonia patients. Sparse blood samples and bronchoalveolar lavage fluid samples were collected from patients after multiple oral doses of 800 mg of contezolid twice a day. Pharmacokinetic parameters were calculated by developing population pharmacokinetic (PopPK) modeling, and probability of target attainment was evaluated by Monte Carlo simulations. The study enrolled 15 patients (mean age 55 years) with primarily community-acquired pneumonia. Contezolid achieved a clinical cure rate of 80.0% and a bacterial clearance rate of 71.4%. Oral contezolid was well tolerated, and no drug-related adverse effects were observed in any of the subjects. The mean area under the concentration-time curve (AUC₀–₁₂,ss) was estimated by the PopPK model to be 33.06 mg·h/L in ELF and 71.95 mg·h/L in plasma. Assuming a plasma protein binding rate of 90% based on literature data, the ELF-to-free plasma AUC0–12,ss ratio was 4.50. When the minimum inhibitory concentration was ≤4 mg/L, 800 mg of contezolid q12h could achieve the optimal therapeutic target in the plasma of patients with pneumonia. This study demonstrates that contezolid achieved excellent pulmonary penetration in adult patients with pneumonia.