ArticleMicrobiology spectrum2026
Cumulative cefepime exposure in cancer patients is associated with an increased risk of ertapenem non-susceptible, meropenem susceptible Enterobacterales bacteremia.
Article in Microbiology spectrum, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Carbapenem resistance in non-carbapenemase producing Enterobacterales can display susceptibility discordance (e.g., ertapenem-non-susceptible, meropenem-susceptible), often in patients with prior antimicrobial use. We aim to characterize risk factors for carbapenem susceptibility discordant Enterobacterales (CSD-E) bloodstream infections in immunocompromised patients. We performed a retrospective, single-center study comparing adults with Enterobacterales BSI who developed subsequent carbapenem susceptibility concordant (CSC; meropenem and ertapenem susceptible) or CSD-E BSI with the same organism within 1 year. Patients who developed subsequent CSD-E BSI were matched to those with repeat CSC-E BSI based on organism. Logistic regression models evaluated CSD-E risk factors. Time-varying covariate Cox proportional hazards models evaluated time-dependent changes in antibiotic exposure when estimating the association between antibiotic use and CSD-E. Comparative genomics of available paired whole-genome sequencing (WGS) data was performed to assess genetic relatedness and antimicrobial resistance (AMR) gene content. Beta-lactam survival mechanisms (BLSM) were assessed via Tolerance Disk Test (TDTest) and Population Analysis Profiling (PAP). We evaluated 829 patients with Enterobacterales BSI. Repeat BSI was CSC-E in 81 patients (9.8%) and CSD-E in 14 patients (1.7%). Matching provided 43 CSC-E controls and 14 CSD-E cases. Univariate analysis revealed any ceftazidime-avibactam (CZA) exposure was associated with developing CSD-E BSI (odds ratio [OR], 7.41; IMPORTANCE: Non-carbapenemase-producing (non-CP) carbapenem-resistant Enterobacterales (CRE) are an important classification of CRE. Increasing rates of non-CP CRE that display carbapenem susceptibility discordance (CSD-E; ertapenem-resistant, meropenem susceptible) have been observed globally and at our institution. Our article aims to characterize risk factors, including cumulative antibiotic exposure, leading to carbapenem susceptibility discordant Enterobacterales (CSD-E) bloodstream infection (BSI) in immunocompromised patients with a history of Enterobacterales BSI. In addition, we analyzed paired whole-genome sequencing data to assess antimicrobial gene content for mechanistic rationales supporting our clinical findings. The risk factors for CSD-E development identified in this study require further validation in multicenter cohorts.
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