Molecular Analysis and Antimicrobial Resistance Pattern of Tigecycline-Non-Susceptible K. pneumoniae Isolated from a Tertiary Care Hospital of East Asia

Abstract

Introduction

Tigecycline is one of the last resorts for carbapenem-resistant K. pneumoniae (CRKP) infections. Indeed, tigecycline-non-susceptible K. pneumoniae (TNSKP) strains are increasingly treated with the use of tigecycline. In this study, we attempted to better understand their epidemiological trends and characteristics. K. pneumoniae were collected from 2017 to 2020 at the First Affiliated Hospital of Nanchang University.

Methods

Thirty-four TNSKP strains were selected during the study period, all of which were analyzed using antimicrobial susceptibility testing, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). PCR and DNA sequencing were performed for the detection of β-lactamase genes and carbapenemase genes, and the mutation analysis of tet(A), tet(X), tet(L), tet(M), rpsJ, ramR, and oqxR, which are related to tigecycline resistance. Virulence gene and capsular genotype testing were conducted to identify whether the TNSKP strains were hypervirulent Klebsiella pneumoniae.

Results

An epidemiology analysis showed that Klebsiella pneumoniae carbapenemase-2 (KPC-2) was the predominant carbapenemase in tigecycline non-susceptible carbapenem-resistant K. pneumoniae (TNSCRKP) (96.7%), and the dominant clone type was ST11-K14K64 (82.4%). Among them, 55.9% (19/34) of strains were from each department of ICU, particularly EICU and neurosurgery ICU. In order to further understand the molecular mechanisms of the TNSKP, a polymerase chain reaction of the resistant determinants was carried out. The results detected many tigecycline-resistant genes, such as tet(A) (97.1%), tet(X) (17.6%), rpsJ (97.1%), and ramR (8.8%).

Conclusion

As the results of this study reveal, we should take effective measures to control the increase in TNSKP.

Keywords:

• carbapenem-resistant
• tigecycline-non-susceptible
• Klebsiella pneumoniae

Abbreviations

CRKP, carbapenem-resistant K. pneumoniae; TNSKP, tigecycline-non-susceptible K. pneumoniae; TNSCRKP, tigecycline non-susceptible carbapenem-resistant K. pneumoniae; PFGE, pulsed-field gel electrophoresis; CLSI, the Clinical and Laboratory Standards Institute; FDA, Food and Drug Administration; MLST, multilocus sequence typing; ST, sequence type; ICU, intensive care unit.

Data Sharing Statement

The data used and/or analyzed in this study are available from the Lingbing Zeng (E-mail: [email protected]) and Junming Li (E-mail: [email protected]) on reasonable request.

Ethics Approval

This study was approved by the Ethics Committee of the first affiliated hospital of Nanchang University (Code: 2014056). All participants in this study provided written informed consent. This study was conducted in accordance with the Declaration of Helsinki.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest.