Global distribution and genomic characteristics of carbapenemase-producing Escherichia coli among humans, 2005-2023

Antibiotic resistance represents a global public health crisis and poses a significant challenge worldwide (Laxminarayan et al., 2016). Carbapenems, an important class of antibiotics, have been widely used to combat infections caused by multidrug-resistant Gram-negative bacteria (van der Bij and Pitout, 2012). Unfortunately, the emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) have severely compromised the efficacy of carbapenems in clinical practice (Nordmann, 2014). The main mechanism of carbapenem resistance in CRE is the acquisition of carbapenemase genes, such as blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48 (Logan and Weinstein, 2017). Carbapenem-resistant Klebsiella and Escherichia coli are the two most common CREs and can cause nosocomial transmission (Zhang et al., 2017).

E. coli is one of the most important pathogens in humans (Vila et al., 2016). However, since E. coli primarily causes community-associated infections in humans, it evades conventional infection prevention measures employed in hospital settings (Pitout, 2021). E. coli serves as a crucial reservoir for antibiotic resistance genes (ARGs) (Leger et al., 2021), and the persistent emergence of multidrug-resistant E. coli greatly limits the use of clinical antimicrobial agents. Carbapenems are recommended for the treatment of multidrug-resistant E. coli infections due to their broad antibacterial spectrum (Zhang et al., 2017). However, the widespread occurrence of CRECs further narrows down the available clinical treatment options.

The epidemiology of CRECs shows a complex and geographically diverse pattern concerning the distribution of carbapenemase genes and dominant lineages (Logan and Weinstein, 2017). CRECs isolated from different countries harbor distinct carbapenemase genes (Dong et al., 2022, Gauthier et al., 2018, Simoni et al., 2019), and their prevalence shows significant global variation. However, there is still a lack of comprehensive studies on the global distribution and genomics of these high-risk CREC isolates (Peirano et al., 2022). In this study, we aimed to systematically survey CREC isolates worldwide using advanced genomic analysis methods. Our findings provide a theoretical basis for understanding the distribution and spread of the carbapenem resistance genes among different countries.

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