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Carbapenem 내성 Klebsiella pneumoniae ST307과 Non-ST307의 분자 특성 및 항균제 내성 비교

Comparison of Molecular Characterization and Antimicrobial Resistance in Carbapenem-Resistant Klebsiella pneumoniae ST307 and Non-ST307

  • 조혜현 (대전과학기술대학교 임상병리과)
  • Hye Hyun Cho (Department of Biomedical Laboratory Science, Daejeon Institute of Science and Technology)
  • 투고 : 2023.10.11
  • 심사 : 2023.12.09
  • 발행 : 2023.12.28

초록

Carbapenem 내성 Klebsiella pneumoniae (Carbapenem-resistant K. pneumonia, CRKP)는 전 세계적인 공중 보건 문제로 대두되고 있다. 최근 Klebsiella pneumoniae carbapenemase-2 (KPC-2) 생성 sequence type (ST)307은 CRKP의 주요 클론으로 확인되었으며, 국내에서 ST307의 확산이 보고되었다. 본 연구에서는 2020년 3월부터 2021년 12월까지 대전지역의 3차 병원에서 분리된 CRKP 50균주를 대상으로, 분자 특성과 항균제 내성 양상을 조사하였다. 역학적 관계는 multilocus sequence typing (MLST)를 통해 분석하였고, 항균제 감수성 검사는 디스크 확산법을 통해 확인하였다. PCR과 DNA 염기서열분석은 carbapenemase 유전자 확인을 위해 수행하였다. CRKP감염은 남성과 60세 이상의 환자에서 훨씬 더 빈번하게 확인되었다. CRKP 50균주 중 46균주(92.0%)는 다제내성(MDR)을 보였고, 44균주(88.0%)는 carbapenemase-producing K. pneumoniae (CPKP)로 확인되었다. 주요 carbapenemase 유형은 KPC-2 (36균주, 72.0%)였으며, New Delhi metallo-enzyme-1 (NDM-1)과 NDM-5는 각각 7균주(14.0%)와 1균주(2.0%)에서 확인되었다. 특히, KPC-2 생성 K. pneumoniae의 88.9% (32/36)가 ST307에 속한 반면, NDM-1,-5 생성 K. pneumoniae의 87.5% (7/8)가 non-ST307에 속한 것을 확인하였다. 이러한 결과는 ST307의 확산 뿐만 아니라 non-ST307의 발달을 예방하기 위한 적절한 감염관리와 효과적인 감시체계가 필요하다고 사료된다.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is emerging as a worldwide public health threat. Recently, Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing sequence type (ST) 307 was identified main clone of CRKP, and dissemination of ST307 was reported in South Korea. This study examined the molecular characteristic and antimicrobial resistance pattern of 50 CRKP isolated from a tertiary hospital in Daejeon, from March 2020 to December 2021. Epidemiological relationship was analyzed by Multilocus sequence typing (MLST) and antimicrobial susceptibility test was determined using disk-diffusion method. PCR and DNA sequence analysis were performed to identify carbapenemase genes. CRKP infections were significantly more frequent in males and the patients aged ≥ 60 years. Among the 50 CRKP isolates, 46 isolates (92.0%) were multidrug-resistant (MDR), and 44 isolates (88.0%) were carbapenemase-producing K. pneumoniae (CPKP). The major carbapenemase type was KPC-2 (36 isolates, 72.0%) and New Delhi metalloenzyme-1 (NDM-1) and NDM-5 were identified in 7 isolates (14.0%) and 1 isolate (2.0%), respectively. In particular, 88.9% (32/36) of KPC-2-producing K. pneumoniae belonged to ST307, whereas 87.5% (7/8) of NDM-1,-5-producing K. pneumoniae belonged to non-ST307. These results suggest that proper infection control and effective surveillance network need to prevent not olny the spread of ST307, but also the development of non-ST307.

키워드

과제정보

This paper was supported by academic research fund offered from Daejeon Institute of Science and Technology in 2023 (DST2023-13).

참고문헌

  1. MacKenzie FM, Forbes KJ, Dorai-John T, Amyes SG, Gould IM. 1997. Emergence of a carbapenem-resistant Klebsiella pneumoniae. Lancet 350: 783.
  2. Deshpande LM, Jones RN, Fritsche TR, Sader HS. 2006. Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000-2004). Microb. Drug Resist. 12: 223-230.
  3. Zheng B, Dai Y, Liu Y, Shi W, Dai E, Han Y, et al. 2017. Molecular epidemiology and risk factors of carbapenem-resistant Klebsiella pneumoniae infections in eastern China. Front. Microbiol. 8: 1061.
  4. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, et al. 2018. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis. 18: 318-327.
  5. Hu Y, Liu C, Shen Z, Zhou H, Cao J, Chen S, et al. 2020. Prevalence, risk factors and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in patients from Zhejiang, China, 2008-2018. Emerg. Microbes Infect. 9: 1771-1779.
  6. Nordmann P, Cuzon G, Naas T. 2009. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect. Dis. 9: 228-236.
  7. Kim SH, Kim GR, Jeong J, Kim S, Shin JH. 2020. Prevalence and characteristics of carbapenemase-producing Enterobacteriaceae in three tertiary-care Korean University hospitals between 2017 and 2018. Jpn. J. Infect. Dis. 73: 431-436.
  8. Kim JH, Cho YY, Choi JY, Wi YM, Ko KS. 2021. Two distinct geno-types of KPC-2-producing Klebsiella pneumoniae isolates from South Korea. Antibiotics 10: 911.
  9. Rhee JY, Park YK, Shin JY, Choi JY, Lee MY, Peck KR, et al. 2010. KPC-producing extreme drug-resistant Klebsiella pneumoniae isolate from a patient with diabetes mellitus and chronic renal failure on hemodialysis in South Korea. Antimicrob. Agents Chemother. 54: 2278-2279.
  10. Yoon EJ, Yang JW, Kim JO, Lee H, Lee KJ, Jeong SH. 2018. Carbapenemase-producing Enterobacteriaceae in South Korea: a report from the National Laboratory Surveillance System. Future Microbiol. 13: 771-783.
  11. Cho HH. 2022. Epidemiological study of KPC-2 producing Klesiella pneumoniae isolated in Daejeon during a 4-year period. Korean J. Clin. Lab. Sci. 54: 265-272.
  12. Cho YY, Kim JH, Kim H, Lee J, Im SJ, Ko KS. 2022. Comparison of virulence between two main clones (ST11 and ST307) of Klebsiella pneumoniae isolates from South Korea. Microorganisms 10: 1827.
  13. Villa L, Feudi C, Fortini D, Brisse S, Passet V, Bonura C, et al. 2017. Diversity, virulence, and antimicrobial resistance of the KPC-producing Klebsiella pneumoniae ST307 clone. Microb. Genom. 3: e000110.
  14. Clinical and Laboratory Standards Institute. 2012. Performance standards for antimicrobial susceptibility testing; twentieth informational supplement, M100-S22. Wayne, Pennsylvania.
  15. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. 2012. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 18: 268-281.
  16. Poirel L, Walsh TR, Cuvillier V, Nordmann P. 2011. Multiplex PCR for detection of acquired carbapenemase genes. Diagn. Microbiol. Infect. Dis. 70: 119-123.
  17. Peirano G, Chen L, Kreiswirth BN, Pitout JDD. 2020. Emerging antimicrobial-resistant high-risk Klebsiella pneumoniae clones ST307 and ST147. Antimicrob. Agents Chemother. 64: e01148-20.
  18. Baker S, Thomson N, Weill FX, Holt KE. 2018. Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens. Science 360: 733-738.
  19. Chang YY, Chuang YC, Siu LK, Wu TL, Lin JC, Lu PL, et al. 2015. Clinical features of patients with carbapenem nonsusceptible Klebsiella pneumoniae and Escherichia coli in intensive care units: a nationwide multicenter study in Taiwan. J. Microbiol. Immunol. Infect. 48: 219-225.
  20. Park JJ, Seo YB, Lee J, Eom JS, Song W, Choi YK, et al. 2020. Positivity of carbapenemase-producing Enterobacteriaceae in patients following exposure within long-term care facilities in Seoul, Korea. J. Korean Med. Sci. 35: e303.
  21. Yoon EJ, Kim JO, Kim D, Lee H, Yang JW, Lee KJ, et al. 2018. Klebsiella pneumoniae Carbapenemase Producers in South Korea between 2013 and 2015. Front. Microbiol. 9: 56.
  22. Habeeb MA, Haque A, Nematzadeh S, Iversen A, Giske CG. 2013. High prevalence of 16S rRNA methylase RmtB among CTX-M extended-spectrum β-lactamase-producing Klebsiella pneumoniae from Islamabad, Pakistan. Int. J. Antimicrob. Agents 41: 524-526.
  23. Fu B, Yin D, Sun C, Shen Y, Liu D, Bai R, et al. 2022. Clonal and horizontal transmission of blaNDM among Klebsiella pneumoniae in children's intensive care units. Microbiol. Spectr. 10: e0157421.
  24. Wu W, Feng Y, Tang G, Qiao F, McNally A, Zong Z. 2019. NDM metallo-β-lactamases and their bacterial producers in health care settings. Clin. Microbiol. Rev. 32: e00115-18.
  25. Guo H, Wu Y, Li L, Wang J, Xu J, He F. 2023. Global emergence of carbapenem-resistant Klebsiella pneumoniae co-carrying multiple carbapenemases. Comput. Struct. Biotechnol. J. 21: 3557-3563.
  26. Shao C, Wang W, Liu S, Zhang Z, Jiang M, Zhang F. 2021. Molecular epidemiology and drug resistant mechanism of carbapenem-resistant Klebsiella pneumoniae in elderly patients with lower respiratory tract infection. Front. Public Health 9: 669173.
  27. Elmanakhly AR, Bendary MM, Safwat NA, Awad EA, Alhomrani M, Alamri AS, et al. 2022. Carbapenem-resistant Klebsiella pneumoniae: diversity, virulence, and antimicrobial resistance. Infect. Drug Resist. 15: 6177-6187.
  28. Jeong SH, Kim HS, Kim JS, Shin DH, Kim HS, Park MJ, et al. 2016. Prevalence and molecular characteristics of carbapenemase-producing Enterobacteriaceae From five hospitals in Korea. Ann. Lab. Med. 36: 529-535.
  29. Park Y, Choi Q, Kwon GC, Koo SH. 2020. Molecular epidemiology and mechanisms of tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae isolates. J. Clin. Lab Anal. 34: e23506.
  30. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, et al. 2001. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 45: 1151-1161.