Year: 2024
Type: article
Study design: Observational Study
Abstract: Background: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. Methods: Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. Results: Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P =. 04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P =. 02) and 90-day (39% vs 0%; P =. 001) mortality compared with MBL-Ec. Conclusions: Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.
DOI: 10.17615/6mzd-fz40
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, Abbott Laboratories, Eli Lilly and Company, Pfizer, AstraZeneca, Gilead Sciences, Teva Pharmaceutical Industries, Infectious Diseases Society of America, Alexion Pharmaceuticals, University of Pennsylvania, Wake Forest University, AtriCure, Case Western Reserve University, Regeneron Pharmaceuticals, BioFire Diagnostics, Entasis Therapeutics, Apellis Pharmaceuticals, Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, Astellas Pharma, Shionogi, Wockhardt, TenNor Therapeutics, National Institutes of Health, Centers for Disease Control and Prevention, Genentech, Samsung, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases
Awards: G143167659, The LiaFSR system and antimicrobial peptide resistance in enterococci, G1801780589, G1825169821, G1840721966, G2328657408, G2363747130, G3448607316, G3889605478, Integrated Genomics of Mucosal Infections, G6790655540, G8367178419, G8623342940, G9000006657, G9000008348, G9000026314, G9000042778, G9000134780
OpenAlex ID: W4400026022