Evolution of tigecycline- and colistin-resistant CRKP (carbapenem-resistant Klebsiella pneumoniae) in vivo and its persistence in the GI tract article

Rong Zhang, Ning Dong, Yonglu Huang, Hongwei Zhou, Miaomiao Xie, Edward Wai Chi Chan, Yanyan Hu, Jiachang Cai, Sheng Chen

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32 Citations (Scopus)


Emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains that also exhibit resistance to tigecycline and colistin have become a major clinical concern, as these two agents are the last-resort antibiotics used for treatment of CRKP infections. A leukemia patient infected with CRKP was subjected to follow-up analysis of variation in phenotypic and genotypic characteristics of CRKP strains isolated from various specimens at different stages of treatment over a period of 3 years. Our data showed that (1) carbapenem treatment led to the emergence of CRKP in the gastrointestinal (GI) tract of the patient, which subsequently caused infections at other body sites as well as septicemia; (2) treatment with tigecycline led to the emergence of tigecycline-resistant CRKP, possibly through induction of the expression of a variant tet(A) gene located in a conjugative plasmid; (3) colistin treatment was effective in clearing CRKP from the bloodstream but led to the emergence of mcr-1-positive Enterobacteriaceae strains as well as colistin-resistant CRKP in the GI tract due to inactivation of the mgrB gene; and (4) tigecycline- and colistin-resistant CRKP could persist in the human GI tract for a prolonged period even without antibiotic selection pressure. In conclusion, clinical CRKP strains carrying a conjugative plasmid that harbors the bla KPC-2 and tet(A) variant genes readily evolve into tigecycline- and colistin-resistant CRKP upon treatment with these two antibiotics and persist in the human GI tract.

Original languageEnglish
Article number127
JournalEmerging Microbes and Infections
Issue number1
Publication statusPublished - 1 Dec 2018

ASJC Scopus subject areas

  • Epidemiology
  • Parasitology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Infectious Diseases
  • Virology

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