Comparative impact of imipenem and meropenem on intestinal carriage and relative fecal abundance of multidrug-resistant bacteria, with detection of residual antibiotics in rectal swabs.

Carbapenems are widely used in critically ill patients, yet their impact on intestinal carriage and relative fecal abundance (RFA) of IMPORTANCE: Carbapenems are essential for the treatment of severe infections caused by multidrug-resistant bacteria, yet their intestinal microbiological consequences remain insufficiently characterized in clinical practice. This study provides direct clinical evidence that imipenem and meropenem, despite similar antibacterial spectra, differ in their intestinal exposure and in their association with changes in targeted cultivable intestinal bacterial populations. By combining culture-based microbiological analyses with direct quantification of fecal carbapenem residues, we demonstrate that meropenem is more frequently detected in the gut and is associated with greater reductions in cultivable Enterobacterales diversity, whereas imipenem is associated with more limited microbiological changes. These findings underscore the relevance of pharmacokinetic determinants and support antimicrobial stewardship strategies that integrate intestinal microbiological consequences alongside clinical efficacy, particularly in high-risk hospitalized patients. These differences were most marked during the first days of therapy, identifying the early treatment interval as the period of greatest perturbation of the intestinal reservoir. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT05516433.