Title: Safety Outcomes of Empiric Linezolid versus Vancomycin in Patients with Pneumonia and Risk Factors for Methicillin-Resistant Staphylococcus aureus Infection
Purpose: Vancomycin and linezolid are primary agents recommended for treating methicillin resistant Staphylococcus aureus pneumonia¹. However, linezolid tends to become the secondary agent during therapy selection due to lack of familiarity, cost, or concern for adverse effects of myelosuppression or serotonin syndrome. The purpose of this study is to investigate key safety outcomes in use of intravenous linezolid and vancomycin for the purpose of inpatient treatment of pneumonia.
Methods: The study was conducted as a single-center, Institutional Review Board (IRB)-approved, retrospective observational cohort study. Patients were identified from clinical data already available in the Ascension central data repository (across 11 practice sites) and screened based on inclusion and exclusion criteria. Encounters were then categorized by receipt of either “vancomycin” or “linezolid,” with further stratification for the various primary and secondary outcomes. The primary outcome is defined as composite safety outcomes, defined as incidences of acute kidney injury, cytopenias, serotonin syndrome, infusion reactions, and suspected or confirmed Clostridioides difficile infection. This data was collected from the facilities’ respective electronic health records for patients admitted between January 1, 2020 to September 30, 2025. Data was analyzed using Student’s t-test or Wilcoxon rank sum test or Chi-square or Fisher’s exact test, as appropriate for the data type. Alpha was set as 0.05 with 80% power.
Results: 14 patients were included in the study from a single site of the 11 sites. The remaining sites are assessed in a separate analysis. 7 patients were in each of the two groups, vancomycin and linezolid. Baseline characteristics were similar between groups. There was no significant difference found between the composite safety outcomes in either treatment group. Within the secondary outcomes, vancomycin patients had a statistically significant increased rate of 30-day all-cause mortality when compared to those of the linezolid group.
Discussion: In this study, we found no significant difference in composite safety outcomes between patients with pneumonia being treated with vancomycin or linezolid. This may represent comparable safety profiles between the agents. It is important to consider the increase in 30-day all-cause mortality rate and apply it to a patient’s full clinical picture. More research is warranted with a larger sample size.
