Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.

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Background Clinical studies have demonstrated inferior cure rates when metronidazole (MTZ) is used to treat Clostridioides difficile infection (CDI). We hypothesized that a newly identified, heme-inducible form of reduced MTZ susceptibility in C. difficile leads to higher odds of initial clinical failure in patients with CDI treated with MTZ. Methods This multicenter cohort study included adults diagnosed with CDI between 2017-18. C. difficile isolated from stool samples underwent agar dilution MTZ susceptibility testing with incorporation of fresh heme. Blinded investigators reviewed medical records for initial clinical failure, defined as the presence of CDI-specific symptoms, a change in CDI therapy due to lack of patient response, and/or CDI-contributable mortality on or before day 6 of treatment, and other relevant clinical variables. Classification and regression tree (CART) analysis was used to identify the MTZ MIC breakpoint that was predictive of initial clinical failure. Results were confirmed using univariate and multivariable logistic regression analyses to account for potential confounders. Results Of the 356 patients included, 72% received MTZ-based therapy and 27% experienced initial clinical failure. CART analysis identified a MTZ MIC ≥1 µg/mL above which patients had a higher rate of initial clinical failure. MTZ MICs ranged from 0.25-8 µg/mL (MIC50/90 = 0.25/2 µg/mL), and approximately 18% of isolates had MTZ MICs ≥1 µg/mL. In multivariable analysis, a MTZ MIC ≥1 µg/mL was an independent predictor of initial clinical failure in patients receiving a MTZ-based treatment regimen (OR, 2.27; 95% CI, 1.19-4.34). Conclusions Using a reproducible method to determine C. difficile MICs to MTZ, a breakpoint of ≥1 µg/mL identified patients at higher risk of initial clinical failure. These are the first data demonstrating poor clinical outcomes associated with reduced MTZ susceptibility in C. difficile.

Background We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of Gram-negative infections (GNI), primarily including carbapenem-resistant Enterobacterales (CRE). Methods This is a real-world, multi-center, retrospective cohort within the United States between 2017-2020. Adult patients who received MEV for ≥ 72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCO) and was examined by multivariable logistic regression analysis (MLR). Results Overall, 126 patients were evaluated from 13 medical centers within ten states. The most common infection source were respiratory tract (38.1%) and intraabdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in four patients; nephrotoxicity (n=2), hepatoxicity (n=1), and rash (n=1). CART-BP between early and delayed treatment was 48 hours (P=0.04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (aOR=0.277, [0.081 – 0.941]). Conclusion Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNI, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCO.