Clinical, microbiological, and genomic characterization of carbapenem-resistant Gram-negative bacteria in bloodstream infection: a multi-center study in Ecuador

AIMS: To evaluate the diversity, prevalence, and phenotypic and genotypic characteristics of carbapenem-resistant Gram-negative bacteria (CR-GNB) causing bloodstream infections, and assess the mechanisms driving their dissemination through a multi-center study in nine hospitals of Ecuador. METHODS AND RESULTS: Between November 2021 and May 2022, 297 Gram-negative bacteria (GNB) were isolated from 273 patients across nine hospitals in Ecuador. Genotypic characterization of carbapenem-resistant GNB from blood cultures was performed by whole genome sequencing (WGS). CR-GNB accounted for 18.8% (56/297), predominantly Klebsiella pneumoniae (41.1%), followed by Enterobacter cloacae complex (16.1%), Acinetobacter baumannii (12.5%), and Pseudomonas aeruginosa (7.1%). CR-GNB showed high resistance to cephalosporins (80%-95%), piperacillin-tazobactam (85.7%), ampicillin-sulbactam (91.1%), and ciprofloxacin (78.6%). Genomic analysis revealed carbapenemase genes blaKPC-2 (most frequent), blaNDM-1, and blaOXA-181 across high-risk clones (e.g. K. pneumoniae ST307, ST258, ST147; A. baumannii ST1187). Carbapenemase genes were plasmid-borne (IncA/C, IncM, IncN, IncF, IncHI2, IncX3, and non-typeable) and associated with transposons (Tn4401, Tn125, and Tn3). Also, blaVIM-2 in Pseudomonas spp. was plasmid- and chromosomally encoded. CONCLUSIONS: Our findings demonstrate a high burden of CR-GNB, primarily due to K. pneumoniae and E. cloacae complex. Furthermore, the widespread distribution of blaKPC-2, blaNDM-1, and blaOXA-181 in high-risk clones, coupled with the frequent plasmid- and transposon-mediated mobilization of these genes, highlights the crucial role of horizontal gene transfer in the dissemination of resistance.