Emergence of NDM-5-Producing Carbapenem-Resistant Klebsiella pneumoniae and SIM-Producing Hypervirulent Klebsiella pneumoniae Isolated from Aseptic Body Fluid in a Large Tertiary Hospital, 2017-2018: Genetic Traits of bla NDM-Like and bla SIM-Like Genes as Determined by NGS

Qi Li; Jiaying Zhu; Jianbang Kang; Yan Song; Donghong Yin; Qian Guo; Junli Song; Yan Zhang; Shuyun Wang; Jinju Duan

doi:10.2147/IDR.S261117

Emergence of NDM-5-Producing Carbapenem-Resistant Klebsiella pneumoniae and SIM-Producing Hypervirulent Klebsiella pneumoniae Isolated from Aseptic Body Fluid in a Large Tertiary Hospital, 2017-2018: Genetic Traits of bla NDM-Like and bla SIM-Like Genes as Determined by NGS

Infect Drug Resist. 2020 Sep 4:13:3075-3089. doi: 10.2147/IDR.S261117. eCollection 2020.

Authors

Qi Li^#¹, Jiaying Zhu^#¹, Jianbang Kang², Yan Song², Donghong Yin², Qian Guo², Junli Song², Yan Zhang³, Shuyun Wang², Jinju Duan²

Affiliations

¹ Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.
² Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.
³ Department of Chief Executive, Willingmed Technology (Beijing) Co., Ltd, Beijing, Beijing, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: To characterize the clinical, resistance, and virulence features of carbapenem-resistant Klebsiella pneumonaie (CRKP) and hypervirulent Klebsiella pneumoniae (hvKP) and also provide an effective selection of drug in CRKP and hvKP treatment.

Materials and methods: Twelve strains were collected and investigated these isolates for their antimicrobial susceptibility and molecular features. Resistance mechanisms, virulence-associated genes, multilocus sequence typing (MLST), and serotypes were detected by PCR and sequencing. Next general sequencing (NGS) was carried out to determine the features of carbapenem resistance and virulence. The synergistic activity of tigecycline-imipenem (TGC+IPM), tigecycline-meropenem (TGC+MEM), and tigecycline-aztreonam (TGC+ATM) combinations were performed by microdilution checkerboard method.

Results: Eleven CRKP and one hvKP strains were collected. All strains showed highly sensitive rates to tigecycline (TGC) and amikacin (AMK). NDM (33.3%, 4/12) was the main resistance mechanism and MLST assigned 3 of them to ST11. CTX-M-producing (n = 1) and KPC-2-producing (n = 1) isolates belonged to ST147 and ST11, respectively. The MICs of ATM and quinolones in NDM-1 CRKP and NDM-5 CRKP strains were different. The serotype of the majority strains was KL22KL137 (58.3%, 7/12), hvKP stain belonged to K64. CRKP strains harbored plasmid-mediated quinolone resistance genes (oqxA, oqxB, qnrS, qnrB), β-lactams (bla _CTX-M-3), aminoglycosides, type I and type III fimbriae genes, siderophore genes, and transporter and pumps. SIM-producing ST1764 K64 showed typical features of hvKP, showing hypermucoviscosity phenotype. The virulence genes, including rmpA2, alls and aerobactin genes, linked to hvKP, were found in ST1764 hvKP. hvKP was sensitive to quinolone; also, oqxA gene was detected. All TGC combinations showed highly synergistic effects and TGC+IPM was more effective treatment.

Conclusion: We first identified the NDM-5-producing ST690 CRKP and SIM-producing ST1764 hvKP strains in Shanxi province. Tigecycline-carbapenem combinations were available treatments for CRKP.

Keywords: Klebsiella pneumoniae; ST1764; blaNDM-5; hypermucoviscous; synergistic effect; tigecycline.