Plasmid-associated clonal expansion drives department-preference transmission of carbapenem-resistant Klebsiella pneumoniae in Xi'an, China: a genomic epidemiology study

Kai Luo¹Shuyan Liu²Jie Feng³Ruichao Li⁴Sirui Zhang²Rong Yu⁵Fang Li¹Yali Li¹Ke Wu⁶Juan Wang⁷Ting Xie⁸Jin'e Lei¹Zhe Yin⁸Lei Han^2*

• ¹The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
• ²Xi'an Jiaotong University, Xi'an, China
• ³College of Life Sciences, Nankai University, Tianjin, China
• ⁴College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China
• ⁵School of Public Health, Xi’an Jiaotong University, Xi'an, Shaanxi, China
• ⁶College of Life Science, Sichuan University, Chengdu, Sichuan Province, China
• ⁷Northwest University, Xi'an, China
• ⁸Beijing Institute of Microbiology and Epidemiology, Beijing, Beijing Municipality, China

Background: The drivers of expanding carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in Northwest China remain poorly understood. This study aimed to investigate the clinical and molecular epidemiology of CRKP infections in Xi'an, China. Methods: We conducted a comprehensive analysis in a tertiary teaching hospital (September 2017– December 2019) by clinical data evaluation, antimicrobial susceptibility testing, and genome sequencing to characterize sequence types (STs), resistance and virulence genes, and plasmid profiles. Results: CRKP isolation rate increased from 3.6% to 17.2% during 2017-2019. Of 140 cases, 31.43% occurred in the Department of Hepatobiliary Surgery and 31 (22.14%) in the ICU, with a predominance among elderly male patients. Surgery and interventional therapy were performed in 50.7% and 25.7% of cases, respectively. Among 23 STs identified, ST11 (72.1%) was the most prevalent and exhibited high rate of multidrug resistance, commonly associated with narrow-spectrum β-lactamases-coding genes (highest in 110/140), blaKPC-2 (106/140), rmtB (85/140), oqxAB (110/140) and fosA (110/140). Virulence factors involved in secretion systems, iron uptake, and adhesion were identified. ST11 strains frequently carried IncFII, IncR and ColRNAI plasmids, while IncFIB-type was more relevant to ST147. Notably, strains harboring plasmid combinations IncFIIpHN7A8:IncR:ColRNAI and IncFIIpHN7A8:IncR:ColRNAI:IncFIB(K)-1-kpn3 were responsible for CRKP infections in the Department of Hepatobiliary Surgery and ICU, and exhibited higher resistance levels to carbapenems. Conclusions: Department-specific plasmid combinations considerably increased CRKP infection and multidrug resistance rates. Surgical and interventional therapies were vital factors contributing to CRKP infections, especially in elderly male patients.