Yonsei Med J.  2016 May;57(3):641-646. 10.3349/ymj.2016.57.3.641.

The Resistance Mechanism and Clonal Distribution of Tigecycline-Nonsusceptible Klebsiella pneumoniae Isolates in Korea

Affiliations
  • 1Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
  • 2Department of Environmental Medical Biology, Yonsei University College of Medicine, Seoul, Korea.
  • 3Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Korea.
  • 4Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea. KSCPJSH@yuhs.ac
  • 5Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
Tigecycline is one of the drugs used to treat multi-drug resistant Klebsiella pneumoniae (K. pneumoniae) infections, including complicated skin and soft tissue infections, complicated intra-abdominal infection, and community-acquired pneumonia in the Republic of Korea. However, since its commercial release, K. pneumoniae resistance against tigecycline has been reported, and there is a serious concern about the spread of tigecycline resistant bacteria.
MATERIALS AND METHODS
In this study, we collected and analyzed 342 isolates from 23 hospitals in the Republic of Korea to determine the mechanisms of tigecycline susceptibility and their clonal types. The hospitals include several from each province in the Republic of Korea, except Jeju, an island province, and nonsusceptibility among the isolates was tested by the disk diffusion method. In our lab, susceptibility was checked again using the broth dilution method, and clonal types were determined using the multilocus sequence typing protocol. Real-time PCR was performed to measure the ramR mutation in the isolates nonsusceptible to tigecycline, which would suggest an increased expression of the AcrAB multidrug pump.
RESULTS
Fifty-six K. pneumoniae isolates were found to be nonsusceptible, 16% of the 342 collected. Twenty-seven and nine isolates of the tigecycline nonsusceptible isolates had mutations in the ramR and rpsJ genes, respectively; while 18 nonsusceptible isolates harbored the tetA gene. Comparison of isolates with and without ramR mutation showed a significant statistical difference (p<0.05) for expression of AcrAB. Moreover, the most common clonal types, as observed in our study, appear to be ST11 and ST789.
CONCLUSION
Several dominate clonal types infer tigecycline resistance to K. pneumoniae, including ST11, ST768, ST15, ST23, ST48, and ST307. There does not seem to be a transferrable medium, such as plasmid, for the resistance yet, although mutation of the ramR gene may be a common event, accounting for 48% of the nonsusceptibility in this study.

Keyword

Tigecycline; Klebsiella pneumoniae; ramR

MeSH Terms

Anti-Bacterial Agents/*pharmacology/therapeutic use
Bacterial Proteins
*Drug Resistance, Bacterial
Humans
Klebsiella Infections/*drug therapy
Klebsiella pneumoniae/*drug effects/genetics/*isolation & purification
Microbial Sensitivity Tests
Minocycline/*analogs & derivatives/pharmacology/therapeutic use
Multilocus Sequence Typing
Plasmids
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Republic of Korea
Anti-Bacterial Agents
Bacterial Proteins
Minocycline

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