Abstract
Carbapenemase-producing Enterobacter (CPEn) has globally emerged to be a severe threat to human health. However, the disease spectrum, impact on affected patients' outcomes, and transmission of CPEn are largely uncharacterized. We performed genome sequencing on a collection of CPEn clinical isolates spanning a six-year period, collating corresponding disease spectrum data and patient prognosis. Among the 128 sequenced CPEn, 2/3 were clinical isolates from a range of infections with bloodstream infections the most common. The remaining isolates were obtained from patient screening and considered to be colonizing the patients. Most (77.6%) CPEn infection isolates were healthcare associated. The predicted in-hospital mortality rate of patients with CPEn infections was 32.9%. We extended our analysis to all publicly available Enterobacter genomes in China to uncover the population structure and transmission of CPEn by phylogenomic analysis. There were 562 CPEn isolated in China among the 14,648 publicly available Enterobacter genomes. Consistent with our local isolates, ST171 E. xiangfangensis encoding bla(NDM-1) or bla(NDM-5) was the most common CPEn type in hospitals across China. Intra-hospital transmission and several inter-hospital and cross-region transmission/strain-movement events of ST171 CPEn were observed. In conclusion, CPEn typically causes healthcare-associated infection and is a severe clinical problem. Countermeasures may need to focus on patient transfer and environmental cleaning including sinks.IMPORTANCECarbapenemase-producing Enterobacter (CPEn) causes difficult-to-treat infections and has emerged globally as a significant antimicrobial resistance threat. Here, we generated genome sequences of 128 CPEn clinical isolates with accompanying clinical data. We found that CPEn causes a variety of infections, typically healthcare associated, and also asymptomatically colonizes patients. Among infections due to CPEn, bacteremia, pneumonia, and urinary tract infection are the most common. CPEn infections lead to a high predicted in-hospital all-cause mortality rate (32.9%). We examined all publicly-available Enterobacter genomes, identified an additional 562 CPEn strains from China, and unveiled the complex population structure of CPEn. We identified multiple intra- and inter-ward transmissions in the hospital and uncovered several inter-hospital and cross-region dissemination of CPEn. Infection control is key to counter CPEn and may need to include enhanced environmental hygiene and measures to reduce transmission related to patient transfer.