1887

Journal of Medical Microbiology logo

Volume 71, Issue 2

Outbreak of KPC-producing ST15 strains in a Chinese tertiary hospital: resistance and virulence analyses No Access

Abstract

Carbapenem-resistant (CRKP) is a major cause of clinical infection. However, carbapenemase (KPC)-producing ST15 strains are occasionally identified and have seldom been reported to cause hospital outbreaks in PR China.

In this study, we describe nosocomial outbreaks caused by KPC-producing ST15 strains in a Chinese tertiary hospital.

To characterize the molecular relationship, resistance and virulence factors of the 32 KPC-producing ST15 strains isolated in a Chinese hospital.

A total of 102 non-repetitive carbapenem-resistant (CRE) strains were collected from a Chinese tertiary hospital in 2018. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to characterize the clonal relationship of the isolates, and the ST15 strains were selected for further study. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Fifteen carbapenem resistance genes, genetic structures and 12 virulence factors were detected by PCR. Whole-genome sequencing (WGS) was performed using next-generation sequencing combined with single-molecule real-time sequencing.

Thirty-two ST15 strains were characterized, and 31 of them presented a PFGE similarity of >92 %, indicating clonal spread. In 81.3 % (26/32) of strains, the imipenem (IPM) and meropenem (MEM) MICs were ≤8 and≤16 µg ml, while only 1 isolate (KP18069) exhibited ≥64 µg ml for both agents. The gene embedded in the Tn-Tn chimaera and synonymous mutations of the gene were detected in all the strains. However, a nonsense mutation at amino acid position 248 (K248X) of OmpK36 was found in the highly carbapenem-resistant strain KP18069. No virulence gene was detected in any of the ST15 strains. WGS analyses further confirmed the genetic characteristics of the KP18069 strain.

Nosocomial outbreaks caused by the clonal spread of ST15 strains were characterized in a Chinese tertiary hospital, and strict monitoring of highly resistant CRKP is required.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): carbapenem , Klebsiella pneumoniae ST15 , KPC-2 , nosocomial outbreaks and resistance gene
Funding
This study was supported by the:
  • National Natural Science Foundation of China (Award 81802044)
    • Principle Award Recipient: JianshengHuang
© 2022 The Authors
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001494
2022-02-14
2024-04-25
Loading full text...

Full text loading...

References

  1. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001; 45:1151–1161 [View Article] [PubMed]
     [Google Scholar]
  2. Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009; 9:228–236 [View Article] [PubMed]
     [Google Scholar]
  3. Zhang R, Liu L, Zhou H, Chan EW, Li J et al. Nationwide surveillance of clinical carbapenem-resistant Enterobacteriaceae (CRE) strains in China. EBioMedicine 2017; 19:98–106 [View Article] [PubMed]
     [Google Scholar]
  4. Zhang Y, Wang Q, Yin Y, Chen H, Jin L et al. Epidemiology of carbapenem-resistant Enterobacteriaceae infections: report from the China CRE Network. Antimicrob Agents Chemother 2018; 62:e01882-17 [View Article] [PubMed]
     [Google Scholar]
  5. Cuzon G, Naas T, Truong H, Villegas MV, Wisell KT et al. Worldwide diversity of Klebsiella pneumoniae that produce beta-lactamase blaKPC-2 gene. Emerg Infect Dis 2010; 16:1349–1356 [View Article] [PubMed]
     [Google Scholar]
  6. Leavitt A, Carmeli Y, Chmelnitsky I, Goren MG, Ofek I et al. Molecular epidemiology, sequence types, and plasmid analyses of KPC-producing Klebsiella pneumoniae strains in Israel. Antimicrob Agents Chemother 2010; 54:3002–3006 [View Article] [PubMed]
     [Google Scholar]
  7. Qi Y, Wei Z, Ji S, Du X, Shen P et al. ST11, the dominant clone of KPC-producing Klebsiella pneumoniae in China. J Antimicrob Chemother 2011; 66:307–312 [View Article] [PubMed]
     [Google Scholar]
  8. Huang J, Ding H, Shi Y, Zhao Y, Wu R et al. Molecular epidemiology of Klebsiella pneumoniae blaKPC gene in Lishui from 2010 to 2016. Chin J Microbiol Immunol 2018; 38:616–622
     [Google Scholar]
  9. Diancourt L, Passet V, Verhoef J, Grimont PAD, Brisse S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol 2005; 43:4178–4182 [View Article] [PubMed]
     [Google Scholar]
  10. Huang Y, Yu X, Xie M, Wang X, Liao K et al. Widespread dissemination of carbapenem-resistant Escherichia coli sequence type 167 strains harboring blaNDM-5 in clinical settings in China. Antimicrob Agents Chemother 2016; 60:4364–4368 [View Article] [PubMed]
     [Google Scholar]
  11. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 1995; 33:2233–2239 [View Article] [PubMed]
     [Google Scholar]
  12. Huang J, Hu X, Zhao Y, Shi Y, Ding H et al. Genetic factors associated with enhanced blaKPC expression in TN3TN4401 chimeras. Antimicrob Agents Chemother 2020e01836–19
     [Google Scholar]
  13. CLSI Performance Standards for Antimicrobial Susceptibility Testing: 27th edn. CLSI Supplement M100 Wayne, PA: Clinical and Laboratory Standards Institute; 2017
     [Google Scholar]
  14. van der Zwaluw K, de Haan A, Pluister GN, Bootsma HJ, de Neeling AJ et al. The carbapenem inactivation method (CIM), a simple and low-cost alternative for the Carba NP test to assess phenotypic carbapenemase activity in gram-negative rods. PLoS One 2015; 10:e0123690 [View Article] [PubMed]
     [Google Scholar]
  15. Pfeifer Y, Cullik A, Witte W. Resistance to cephalosporins and carbapenems in Gram-negative bacterial pathogens. Int J Med Microbiol 2010; 300:371–379 [View Article] [PubMed]
     [Google Scholar]
  16. Huang J, Li X, Zhu N, Li G. Genetic characteristics of one highly multi-drug-resistant strain of Klebsiella ozaenae. J Med Microbiol 2012; 61:1303–1305 [View Article] [PubMed]
     [Google Scholar]
  17. Zhang Y, Zhao C, Wang Q, Wang X, Chen H et al. High prevalence of hypervirulent Klebsiella pneumoniae infection in China: geographic distribution, clinical characteristics, and antimicrobial resistance. Antimicrob Agents Chemother 2016; 60:6115–6120 [View Article] [PubMed]
     [Google Scholar]
  18. Gu D, Dong N, Zheng Z, Lin D, Huang M et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis 2018; 18:37–46 [View Article] [PubMed]
     [Google Scholar]
  19. Li X, Ma W, Qin Q, Liu S, Ye L et al. Nosocomial spread of OXA-232-producing Klebsiella pneumoniae ST15 in a teaching hospital, Shanghai, China. BMC Microbiol 2019; 19:235 [View Article] [PubMed]
     [Google Scholar]
  20. Li R, Cheng J, Dong H, Li L, Liu W et al. Emergence of a novel conjugative hybrid virulence multidrug-resistant plasmid in extensively drug-resistant Klebsiella pneumoniae ST15. Int J Antimicrob Agents 2020; 55:105952 [View Article] [PubMed]
     [Google Scholar]
  21. Han Y, Huang L, Liu C, Huang X, Zheng R et al. Characterization of carbapenem-resistant Klebsiella pneumoniae ST15 clone coproducing KPC-2, CTX-M-15 and SHV-28 spread in an intensive care unit of a tertiary hospital. Infect Drug Resist 2021; 14:767–773 [View Article] [PubMed]
     [Google Scholar]
  22. Sheu CC, Chang YT, Lin SY, Chen YH, Hsueh PR. Infections caused by carbapenem-resistant Enterobacteriaceae: an update on therapeutic options. Front Microbiol 2019; 10:80 [View Article] [PubMed]
     [Google Scholar]
  23. Berglund B, Hoang NTB, Tärnberg M, Le NK, Nilsson M et al. Molecular and phenotypic characterization of clinical isolates belonging to a KPC-2-producing strain of ST15 Klebsiella pneumoniae from a Vietnamese pediatric hospital. Antimicrob Resist Infect Control 2019; 8:156 [View Article] [PubMed]
     [Google Scholar]
  24. Wong JLC, Romano M, Kerry LE, Kwong HS, Low WW et al. OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo. Nat Commun 2019; 10:3957 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001494
Loading
Outbreak of KPC-producing Klebsiella pneumoniae ST15 strains in a Chinese tertiary hospital: resistance and virulence analyses
J. Med. Microbiol. 71, 001494 (2022); https://doi.org/10.1099/jmm.0.001494
/content/journal/jmm/10.1099/jmm.0.001494
/content/journal/jmm/10.1099/jmm.0.001494
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error