The clinical impact and dissemination of carbapenemase-producing <i>Enterobacter</i> : a genome-based study in China

Carbapenemase-producing <i>Enterobacter</i> (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 <i>Enterobacter</i> 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 <i>Enterobacter</i> genomes. Consistent with our local isolates, ST171 <i>E. xiangfangensis</i> encoding <i>bla</i>_NDM-1 or <i>bla</i>_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 <i>Enterobacter</i> (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 <i>Enterobacter</i> 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.