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.

UNLABELLED: Carbapenems are widely used in critically ill patients, yet their impact on intestinal carriage and relative fecal abundance (RFA) of Enterobacterales, Enterococcus spp., Pseudomonas aeruginosa, and Clostridioides difficile remains poorly characterized. We compared the effects of imipenem and meropenem on these targeted bacterial populations and on carriage of resistant organisms. Eighty-three hospitalized patients receiving imipenem (n = 52) or meropenem (n = 31) were included. Rectal samples were collected before treatment (T0), at 48-72 h (T1), and at the end of therapy (T2). Culture-based methods assessed changes in cultivable species, RFA, and carriage of multidrug-resistant organisms. Fecal carbapenem residues and degradation products were quantified by ultra-high performance liquid chromatography-high-resolution mass spectrometry. Longitudinal changes were compared between treatment groups and according to fecal antibiotic detection. At T1, RFA of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) was higher with meropenem than imipenem (95% vs 32%, P = 0.007), with no difference at T2. Between T0 and T1, the number of cultivable Enterobacterales species decreased more frequently in the meropenem group (57.1% vs 21.9%, P = 0.018). Antibiotic was detected in rectal samples of 59.1% of meropenem-vs 25.8% of imipenem-treated patients; the most marked changes occurred in meropenem-treated patients with detectable residues. 3GCR-E carriage persisted under both treatments at T2 (imipenem 28.6%, meropenem 58.3%, P = 0.092). Imipenem was associated with lower intestinal exposure and more limited changes in targeted cultivable intestinal bacterial populations than meropenem. Pharmacokinetic differences may drive differential intestinal microbiological effects of carbapenems, supporting stewardship strategies that account for intestinal consequences. 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.