Prolonged linezolid therapy induces progressive mitochondrial dysfunction in human peripheral blood mononuclear cells.
Level 3 - non-randomized controlled study
Non-randomized observational cohort study stratified by duration of drug exposure
PubMed 42265784 · doi:10.1186/s12967-026-08406-5
What was done
Forty patients treated with linezolid were stratified into three groups based on treatment duration: 2-7 days (group 1), 8-14 days (group 2), and >14 days (group 3). Mitochondrial function in peripheral blood mononuclear cells (PBMCs) was assessed using Seahorse XF metabolic flux analysis. Protein expression alterations were analyzed by LC-MS/MS, with differentially expressed proteins defined by |log₂FC| ≥ 0.58 and p < 0.05, followed by STRING interaction network mapping.
What was found
The abstract reports no absolute values, effect estimates, or confidence intervals. It reports that PBMC mitochondrial respiration declined progressively with longer treatment duration in parallel with decreasing platelet counts. Proteomic profiling showed one cluster of downregulated proteins in group 2 and two clusters in group 3, primarily involving subunits of respiratory chain complexes I and IV related to mitochondrial ATP synthesis.
Why it matters
It provides human ex vivo evidence linking duration of linezolid exposure to progressive mitochondrial respiratory decline and identifies complex I involvement alongside known complex IV inhibition.
Limits
Small sample size (n = 40) split across three duration strata without longitudinal pre-treatment baseline data. The abstract provides no exact quantitative values or confidence intervals for respiration rates or platelet counts, and clinical indications and co-medications were not detailed.
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