Phenotypic and Genotypic Characterization of Carbapenem-Resistant Enterobacteriaceae Recovered from a Single Hospital in China, 2013 to 2017

Yan Zhang,1 Wenjie Li,1 Xiaomin Tian,1 Ruanyang Sun,1 Shidan Zhou,2 Ling Jia,1 Jian Sun,1,3,4 Xiao-Ping Liao,1,3,4 Ya-Hong Liu,1,3,4 Yang Yu1,3,4 1Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, People’s Republic of China; 2Intensive Care Unit, Huizhou Municipal Central Hospital, Huizhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Microbial Safety and Health, Guangdong Institute of Microbiology, Guangdong Academy of Science, Guangzhou, People’s Republic of China; 4Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, People’s Republic of ChinaCorrespondence: Yang Yu, Email graceyyu@scau.edu.cnObjective: Carbapenem-resistant Enterobacteriaceae (CRE) have become an increasingly common cause of healthcare-related infections and present a serious challenge to clinical treatment. This study examined the phenotypic, genotypic characterization, clinical, and microbiological data of CRE in the Huizhou Municipal Central Hospital.Methods: We conducted a phenotypic susceptibility evaluation and whole genome sequence analysis for 52 CRE strains isolated from 37 patients and 2 medical device-related samples during 2013– 2017 to characterize risk factors, antimicrobial resistance profiles, dominant clones and hospital transmission.Results: Long-term hospitalization, treatment time with antibiotics and use of invasive devices were linked to the risk of CRE infection. The carbapenem resistance genes (CRGs) we found included blaNDM (82.7%), blaIMP (19.2%) and blaKPC (3.8%), Escherichia coli (44.2%) and Klebsiella pneumoniae (44.2%) were the dominant species we identified, and the type of CRG carried by isolates was highly correlated with species. The coexistence of CRGs with a variety of other antibiotic resistance genes leads to an increased prevalence of high resistance levels for CRE to β-lactams and other antibiotic classes such as aminoglycosides and fluoroquinolones. These isolates were sensitive only to colistin and tigecycline. In addition to this, we observed significantly genomic diversity of CRE isolates in this hospital. Importantly, we found that long-term transmission of multiple CRE clones had occurred at this hospital between various wards.Conclusion: Evaluating and improving the current infection control strategies may be necessary, and reducing nosocomial transmission remains the primary control element for CRE infections in China.Keywords: carbapenem-resistant Enterobacteriaceae, bacteremia, carbapenem resistance genes, nosocomial transmission