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

 Chulsoo Ahn  ;  Sang Sun Yoon  ;  Tae Soon Yong  ;  Seok Hoon Jeong  ;  Kyungwon Lee 
 YONSEI MEDICAL JOURNAL, Vol.57(3) : 641-646, 2016 
Journal Title
Issue Date
Anti-Bacterial Agents/pharmacology* ; Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins ; Drug Resistance, Bacterial* ; Humans ; Klebsiella Infections/drug therapy* ; Klebsiella pneumoniae/drug effects* ; Klebsiella pneumoniae/genetics ; Klebsiella pneumoniae/isolation & purification* ; Microbial Sensitivity Tests ; Minocycline/analogs & derivatives* ; Minocycline/pharmacology ; Minocycline/therapeutic use ; Multilocus Sequence Typing ; Plasmids ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Republic of Korea
Klebsiella pneumoniae ; Tigecycline ; ramR
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.
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1. College of Medicine (의과대학) > Dept. of Tropica Medicine (열대의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yong, Tai Soon(용태순) ORCID logo https://orcid.org/0000-0002-3445-0769
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
Lee, Kyungwon(이경원) ORCID logo https://orcid.org/0000-0003-3788-2134
Jeong, Seok Hoon(정석훈) ORCID logo https://orcid.org/0000-0001-9290-897X
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