Clinical Impact of New Delhi Metallo-Beta-Lactamase-Producing Enterobacterales in Critically Ill Patients: Are We Ready to Face the Challenge?

Background: Carbapenem-resistant Enterobacterales infections are frequent in critically ill patients. Outbreaks caused by carbapenemase-producing Enterobacterales, in particular the New Delhi Metallo-beta-lactamase (NDM)-type carbapenemase-producing phenotype, are increasing in Italy. Unfortunately, the clinical impact of this new microorganism is still being defined, as well as the correlation between colonization and invasive infections. The aim of the study is to analyze factors related to the development of NDM infections in colonized patients and to evaluate their impact on patients' outcome in high-complexity ICUs. Methods: All patients admitted to the General and Cardiac ICUs of 'Citt & agrave; della Salute e della Scienza' University Hospital in Turin (Italy) between January and August 2023 were enrolled. Microorganisms were examined by lateral flow immunochromatographic assays or molecular assays on weekly surveillance or clinically requested cultures. Antimicrobial susceptibility was determined by broth microdilution methods and interpreted according to EUCAST breakpoints. Results: Out of a total of 915 patients, 46 (5%) were positive for NDM-producing Enterobacterales and, among them, 13 (28%) developed an invasive infection. All patients were critical (SAPS II 40+/-13). The median times between ICU admission and colonization or infection were 6 and 16 days, respectively. Significant disparities emerged between colonized and infected patients regarding days of mechanical ventilation (1 vs. 28), ICU (7 vs. 39 days), and in-hospital (21 vs. 71 days) length of stay. Renal replacement treatment (OR 8.2461, p = 0.0173, 95% CI [1.3636-65.9114]) and surgery (OR 22.8747, p = 0.0149, CI95% [1.5986-1447.743]) seemed to impact the risk of developing infection. Six patients with invasive infection were treated with Cefiderocol and five with Ceftazidime/Avibactam and Aztreonam. In absence of early identification and appropriate treatment, patients may be at increased risk of colonization spread and potentially worse clinical outcomes. Conclusions: Early identification of the carbapenemase type is clinically relevant in critically ill patients with confirmed or suspected infection, as NDM production necessitates the use of specific agents for effective treatment.