Tuberculosis and Respiratory Diseases

  • 제85권3호
  • /
  • Pages.256-263
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  • 2022
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  • 1738-3536(pISSN)
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  • 2005-6184(eISSN)
대한결핵및호흡기학회 (The Korean Academy of Tuberculosis and Respiratory Diseases)
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Susceptibility of β-Lactam Antibiotics and Genetic Mutation of Drug-Resistant Mycobacterium tuberculosis Isolates in Korea

  • Park, Sanghee (Clinical Research Center, Masan National Tuberculosis Hospital) ;
  • Jung, Jihee (Clinical Research Center, Masan National Tuberculosis Hospital) ;
  • Kim, Jiyeon (Clinical Research Center, Masan National Tuberculosis Hospital) ;
  • Han, Sang Bong (Department of Laboratory Medicine, Masan National Tuberculosis Hospital) ;
  • Ryoo, Sungweon (Clinical Research Center, Masan National Tuberculosis Hospital)
  • 투고 : 2021.12.23
  • 심사 : 2022.05.17
  • 발행 : 2022.07.31
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초록

Background: Mycobacterium tuberculosis (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with clavulanate, a β-lactamase inhibitor, was effective in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). However, in Korea, clavulanate can only be used as drugs containing amoxicillin. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients. Methods: The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets blaC, blaI, ldtA, ldtB, dacB2, and crfA were analyzed by polymerase chain reaction and DNA sequencing. Results: The MIC90 values of amoxicillin/clavulanate and meropenem/clavulanate in drug-resistant Mtb isolates were 64/2.5 and 16/2.5 mg/L, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation was found in the blaC gene related to β-lactam antibiotics' high susceptibility. Conclusion: Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

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과제정보

We thank the staff and researchers of the clinical research center and department of laboratory medicine of Masan National Tuberculosis Hospital.

참고문헌

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