Characterization of ST11 and ST15 Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae from Patients with Ventilator-Associated Pneumonia

Abstract

Shuang Song,1,2,* Shulong Zhao,2,* Wei Wang,1 Fei Jiang,2 Jingfang Sun,2 Ping Ma,1,2 Haiquan Kang2 1Medical Technology School, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiquan Kang, Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel [phone], Email [email protected] Ping Ma, Medical Technology School, Xuzhou Medical University, Department of Laboratory Medicine, Xuzhou, People’s Republic of China, Tel [phone], Email [email protected]: The prevalence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (hv-CRKP) is a serious public threat globally. Here, we performed clinical, molecular, and phenotypic monitoring of hv-CRKP strains isolated from the intensive care unit (ICU) to offer evidence for prevention and control in hospitals.Methods: Data analysis of ICU patients suffering from ventilator-associated pneumonia (VAP) because of hv-CRKP infection, admitted at the Chinese Teaching Hospital between March 2019 and September 2021 was performed. Patients’ antibiotic-resistance genes, virulence-associated genes, and capsular serotypes of these isolates were detected. Homology analysis of the strains was performed by MLST and PFGE. Six different strains were tested for their virulence traits using the serum killing test and the Galleria mellonella infection assay. For whole genome sequencing, KP3 was selected as a representative strain.Results: Clinical data of 19 hv-CRKP-VAP patients were collected and their hv-CRKP were isolated, including 10 of ST11-KL64, 4 of ST15-KL112, 2 of ST11-KL47, 1 of ST15-KL19, 1 of ST17-KL140, and 1 of ST48-KL62. Four ST15 and 8 ST11 isolates revealed high homology, respectively. Most strains carried the carbapenemase gene blaKPC-2 (14/19, 73.68%), followed by blaOXA-232 (4/19, 21.05%). All strains were resistant to almost all the antibiotics except polymyxin and tigacycline. Ten patients were treated with polymyxin or tigacycline based on their susceptibility results, and unfortunately 6 patients died. All strains exhibited a hyper-viscous phenotype, and the majority (17/19, 89.47%) of them contained rmpA and rmpA2. The serum killing test showed that KP9 was resistant to normal healthy serum, others were intermediately or highly sensitive. G. mellonella larvae infection assay suggested that the strains in this study were hypervirulent.Conclusion: This study highlights the dominant strain and molecular epidemiology of hv-CRKP in a hospital in China. We should pay more attention to the effect of hv-CRKP on VAP, strengthen monitoring and control transmission.Keywords: Klebsiella pneumoniae, hypervirulent, carbapenem-resistant, ventilator-associated pneumonia

Keywords

• klebsiella pneumoniae
• hypervirulent
• carbapenem-resistant
• ventilator-associated pneumonia