Clinical Features and Outcomes of Infections Caused by Metallo-β-Lactamase-Producing Enterobacterales: A 3-Year Prospective Study From an Endemic Area

Abstract

Background: Metallo-β-lactamase (MBL)-producing Enterobacterales are increasing worldwide. Our aim was to describe clinical features, treatments, and outcomes of infections by MBL-Enterobacterales.

Methods: A prospective observational study conducted in the Pisa University Hospital (January 2019 to October 2022) included patients with MBL-producing Enterobacterales infections. The primary outcome measure was the 30-day mortality rate. Multivariable Cox regression analysis was performed to identify factors associated with that mortality rate, and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated.

Results: The study's 343 patients included 15 with Verona integron-encoded MBL (VIM)- and 328 with New Delhi MBL (NDM)-producing Enterobacterales infections; there were 199 patients (58%) with bloodstream infections, 60 (17.5%) with hospital-acquired or ventilator-associated pneumonia, 60 (17.5%) with complicated urinary tract infections, 13 (3.8%) with intra-abdominal infections, and 11 (3.2%) with skin and soft-tissue infections. The 30-day mortality rate was 29.7%. Of 343 patients, 32 did not receive in vitro active antibiotic therapy, 215 (62.7%) received ceftazidime-avibactam plus aztreonam, 33 (9.6%) received cefiderocol-containing regimens, 26 (7.6%) received colistin-containing regimens, and 37 (10.8%) received other active antibiotics. On multivariable analysis, septic shock (aHR, 3.57 [95% CI, 2.05-6.23]; P < .001) and age (1.05 [1.03-1.08]; P < .001) were independently associated with the 30-day mortality rate, while in vitro active antibiotic therapy within 48 hours after infection (0.48 [.26-.8]; P = .007) and source control (0.43 [.26-.72]; P = .001) were protective factors. Sensitivity analysis showed that ceftazidime-avibactam plus aztreonam, compared with colistin, was independently associated with a reduced 30-day mortality rate (aHR, 0.39 [95% CI, .18-.86]; P = .02). Propensity score analyses confirmed these findings.

Conclusions: MBL-producing carbapenem-resistant Enterobacterales infections are associated with high 30-day mortality rates. Patients with MBL-producing Enterobacterales infections should receive early active antibiotic therapy.

Keywords: Klebsiella pneumoniae; Enterobacterales; aztreonam; metallo-β-lactamase.