Systematic review and meta-analysis to identify meropenem exposures and pharmacological targets predictive of clinical outcomes.

Abstract

Background: Meropenem is a broad-spectrum carbapenem reserved for severe infections. Pharmacokinetic variability has been observed in meropenem patients, and its optimal pharmacological target remains unclear. This meta-analysis evaluated meropenem exposure, target attainment, and their association with clinical outcomes to clarify effective pharmacological targets.

Methods: Following PRISMA (PROSPERO CRD42024499652), studies were identified that measured meropenem concentrations in patient samples and reported clinical outcomes. Studies were synthesized and predictors for clinical outcomes were identified by meta-analysis. Patient-level data, provided by authors, were analysed by multivariate logistic regression to identify predictors for clinical outcomes.

Results: In total, 42 studies were included, comprising 2264 patients. Most studies had a high risk of bias in this context. Pooled clinical cure was 70.0% and 30-day mortality 22.2%. Meropenem concentration was not associated with clinical cure (OR 1.01 per mg/L, 95% CI 0.97-1.05, P = 0.702), whereas attaining 100%ƒT > MIC was marginally associated with cure (OR 1.02 per 1%, 1.00-1.04, P = 0.0552). Higher meropenem exposure was associated with increased 30-day mortality (OR 1.064 per mg/L, 1.008-1.124, P = 0.025). In patient-level analysis (six studies, 295 patients), meropenem exposure, SOFA score and age were each independently associated with mortality.

Discussion: Higher meropenem concentrations were associated with increased mortality across both cohort and patient-level analyses, challenging the assumption that universally higher dosing benefits all patients. However, residual confounding by illness severity could not be excluded, thus this finding should be considered hypothesis generating. Attaining 100%ƒT > MIC may improve cure while avoiding excessive concentrations may reduce harm, further research into meropenem personalized dosing is required.