Abstract

BACKGROUND. The IDSA Antimicrobial Resistance Treatment Guidance suggests that Enterobacterales infections resistant to ertapenem -but susceptible to meropenem or imipenem- can be effectively treated with the latter two agents, when a carbapenemase is not present. Clinical outcomes data to support this suggestion are lacking. METHODS. We investigated this question using a cohort of 379 patients with invasive Enterobacterales infections hospitalized between 2018-2024 at three tertiary-care hospitals in Chile. The unexposed and exposed group included patients with ertapenem-susceptible (ETP-S) and ertapenem-resistant (ETP-R) isolates, respectively. Patients with ETP-S (but ceftriaxone-resistant) infections were selected as the unexposed group as a proxy for extended-spectrum β-lactamase producing Enterobacterales (ESBL-E) – for which meropenem or imipenem are preferred based on clinical trial data. Eligibility criteria included: (1) patients treated with meropenem or imipenem-cilastatin, (2) isolates susceptible to meropenem or imipenem by broth microdilution, and (3) isolates negative for carbapenemase genes by PCR analysis. Inverse probability weighting (IPW) was employed to reduce selection bias between treatment groups. Logistic regression using the IPW cohort was used to generate odds ratios and 95% confidence intervals to investigate 14-day and 3-day mortality between both treatment groups. RESULTS. The cohort included 234 (62%) ETP-S and 145 (38%) ETP-R patients. The most frequently identified bacterial species were Klebsiella spp. (60% in the ETP-S group vs. 93% in the ETP-R group), Escherichia coli (35% vs. 1%), and Enterobacter spp. (3% vs. 5%). Although some differences existed in the overall cohort, baseline characteristics were well-balanced in the IPW cohort (Table 1). In the IPW cohort, 30-day mortality was significantly lower in the ETP-S group (OR: 0.58, 95% CI: 0.34–0.98, p=0.042). A non-significant trend towards lower 14-day mortality was also observed in the ETP-S group (OR: 0.62, 95% CI: 0.34–1.13, p=0.117). CONCLUSION. Our findings suggest patients with invasive infections due to non-carbapenemase producing ETP-R Enterobacterales exhibit suboptimal outcomes when treated with meropenem or imipenem. The high frequency of this phenotype (i.e., ETP-R, meropenem/imipenem-susceptible) calls for further investigation to address this question in a larger interventional cohort.