Linezolid-induced lactic acidosis in critically ill patients: A multicentre study of incidence, severity and...

Linezolid, a synthetic oxazolidinone for resistant gram-positive infections, is generally associated with mild adverse effects such as gastrointestinal disturbances, but more serious reactions like lactic acidosis (LA) have also been reported. LA may be more pronounced in critically ill patients; therefore, this study aims to determine the incidence, severity and predictors of linezolid-associated LA in this vulnerable population.

We conducted a retrospective observational study of adult ICU patients receiving linezolid from January 2021 to May 2025. Data on demographics, comorbidities, linezolid regimen, concomitant medications and laboratory values were collected. Multivariate logistic regression was used to identify predictors of LA.

Of 904 patients screened, 551 were included (mean age 56 years; 73.3% male). LA occurred in 10.7% (n = 59) and was classified as moderate (22%), severe (49%) or critical (29%), with a mean onset of 4 days. Independent predictors of LA included linezolid at a daily dose of 600 mg (aOR = 50.4; p = 0.028), sepsis (aOR = 2.61; p = 0.042), infections other than pneumonia (aOR = 4.0; p = 0.042) and the use of norepinephrine (aOR = 3.56; p = 0.005).

Linezolid-associated lactic acidosis is a frequent and often severe complication in ICU patients, typically developing early during therapy. Sepsis, non-pneumonia infections and norepinephrine use were identified as key risk factors. These findings highlight the need for early recognition and vigilant monitoring of high-risk patients to promote safer use of linezolid in critically ill populations.