A Nosocomial Respiratory Infection Outbreak of Carbapenem-Non-Susceptible Escherichia coli ST131 with Multiple Transmissible blaKPC-2 Carrying Plasmids

Background: Escherichia coli sequence type (ST) ST131 is one of the most widespread and successful opportunistic pathogenic E. coli clones known as multiple-resistance. It can cause community- and hospital-acquired urinary tract infection, abdominal and pelvic infection, and bacteraemia with high morbidity and mortality. Currently, carbapenems have been considered the treatment of choice for E. coli ST131 infections. Although carbapenem resistance is still rare, the resistance rate to carbapenems is growing slowly mainly due to the acquisition of β-lactamase and carbapenemase. In this study, we report a nosocomial outbreak of predominantly respiratory infections caused by blaKPC-2 carrying E. coli ST131 in a Chinese hospital and revealed the transmission of carbapenem-non-susceptible E. coli, as well as the acquisition and spread of blaKPC-2 by E. coli ST131.   Methods: A total of 45 carbapenem-non-susceptible E.coli strains were collected in one Beijing hospital from July 2012 to December 2013. The characteristic of these strains including antimicrobial susceptibility, carbapenem resistance mechanism, plasmid profiles and genetic background were determined by two-fold broth microdilution method, PCR, PFGE-S1 southern blot hybridization and whole genome sequencing respectively. Phylogenetic relationships between these strains were inferred. The genetic context of blaKPC-2 was analyzed to trace the spread of blaKPC-2.   Findings: 45 carbapenem-non-susceptible E. coli strains were isolated from patients mainly with respiratory infections in this nosocomial outbreak. These strains carried blaKPC-2 and belonged to ST131. These strains are closely related and divided into multiple lineages in the phylogenetic tree. It was initially prevalent only in the ward E02, then spread to other wards and multiple lineages co-evolved, resulting in a nosocomial respiratory infection outbreak of carbapenem-non-susceptible E. coli ST131 in these geriatric wards. The blaKPC-2 positive plasmid profiles suggested that the carbapenem resistance was due to the acquisition of multiple transmissible plasmids carrying blaKPC-2 by E. coli ST131. These plasmids with different backbone sequence exhibit wealthy multidrug resistance (MDR) regions and cointegrate structure at the mediate of IS26. Diverse multidrug resistance elements were transferred and rearranged between these plasmids with different backbone sequence at the mediate of IS26, resulting in the rapid spread of antibiotic-resistant genes and blaKPC-2 between these strains.   Interpretation: E. coli ST131 has become a multidrug epidemic clone that can cause hospital-acquired respiratory infections that have been less aware. Our research indicates that clinical attention should be paid to the importance of E. coli ST131 in respiratory infections. The emergence of blaKPC in E. coli ST131 may herald the beginning for transmission of blaKPC with high prevalence in communities and hospitals. Close monitoring of blaKPC-2 positive ST131 in hospitals and communities are necessary for control and proper treatment of ST131 infections.   Funding Statement: This work was supported by the National Natural Science Foundation of China (81861138053，31761133004 and 81861138004) and the Ministry of Science and Technology (2018ZX10733-402). Declaration of Interests: All authors declare that there are no conflicts of interest. Ethics Approval Statement: Not needed.