대한임상검사과학회지 (Korean Journal of Clinical Laboratory Science)

  • 제51권4호
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  • Pages.428-435
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  • 2019
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  • 1738-3544(pISSN)
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  • 2288-1662(eISSN)
대한임상검사과학회 (Korean Society for Clinical Laboratory Science)
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분자학적 방법을 이용한 Carbapenemase-Producing Klebsiella oxytoca 검출

Carbapenemase-Producing Klebsiella oxytoca Detection Using Molecular Methods

  • 양병선 (진주보건대학교 임상병리과) ;
  • 박지애 (진주보건대학교 임상병리과)
  • Yang, Byoung Seon (Department of Medical Laboratory Science, Jinju Health College) ;
  • Park, Ji Ae (Department of Medical Laboratory Science, Jinju Health College)
  • 투고 : 2019.10.01
  • 심사 : 2019.11.01
  • 발행 : 2019.12.31
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초록

Klebsiella pneumoniae carbapenemase (KPC)와 같은 carbapenem 분해효소의 급속한 증가와 보급은 의료 관련 감염 분야 내에서 주요한 문제가 되었다. Carbapenem-resistant Enterobacteriaceae (CRE) 감염을 치료하기 위한 항생제는 거의 없으므로 내성의 박테리아 메커니즘의 확인은 감염 통제와 역학 연구에 매우 중요하다. 그러므로 KPC 균주를 검출하는 신속하고 효과적인 방법은 치료상의 실패를 피하고, 이러한 다제 내성세균의 유통을 방지 및 통제하는 대책으로 도입할 필요가 있다. 분석에 이용한 31균주에서 Acinetobacter spp. 7균주, Morganella morganii 6균주, Pseudomonas aeruginosa 5균주, Proteus mirabilis 5균주, Proteus vulgaris 1균주, Enterobacter cloacae 2균주, Enterobacter aerogenes 1균주, Klebsiella pneumoniae 1균주, Klebsiella oxytoca 1균주, Serratia marcescens 1균주, Escherichia coli 1균주를 확인하였다. 그람음성 간균이 분리된 검체의 빈도는 urine (35.5%), blood (19.4%), sputum (16.1%), pus (9.7%), ascitic fluid (9.7%), tracheal aspirates (6.5%), bile juice (3.2%) 순으로 나타났다. PCR 방법을 이용한 유전자분석 결과 blaIMP, blaVIM, blaOXA-48 에서는 증폭이 확인된 균주가 없었으나, Klebsiella oxytoca 1 균주에서 blaKPC 유전자를 확인하였다. 결론적으로, PCR 방법을 이용한 진단법은 KPC를 정확하고 신속하게 진단할 수 있으며, 그로 인해 병원 내 KPC의 전파방지를 위한 신속한 예방대책 수립이 가능하다 할 수 있다.

The rapid increase and dissemination of carbapene mases, such as Klebsiella pneumoniae carbapenemase (KPC), has become a major problem within the field of healthcare-related infection. There are few antibiotics to treat carbapenem-resistant Enterobacteriaceae (CRE) infections, so the identification of resistant bacterial mechanisms is critical to initiate infection control and conduct epidemiological research. A rapid and effective method for detecting KPC-producing bacteria is needed to avoid therapeutic failures and introduce measures to prevent and control the dissemination of these multi-resistant bacteria. During the study period, 31 isolates (seven isolates of Acinetobacter spp., six isolates of Morganella morganii, five isolates of Pseudomonas aeruginosa, five isolates of Proteus mirabilis, one isolate of Proteus vulgaris, two isolates of Enterobacter cloacae, one isolate of Enterobacter aerogenes, one isolate of Klebsiella pneumoniae, one isolate of Klebsiella oxytoca, one isolate of Serratia marcescens and one isolate of Escherichia coli) were identified by the VITEK. Gram negative rod bacteria were the most frequently isolated from urine (35.5%), blood (19.4%), sputum (16.1%), pus (9.7%), ascitic fluid (9.7%), tracheal aspirates (6.5%) and bile juice (3.2%). Analysis using the PCR method identified the blaKPC gene in the K. oxytoca1 strain, but the blaIMP, blaVIM and blaOXA-48 genes are not amplified. In conclusion, diagnosis using the PCR method can accurately and quickly diagnose KPC, thus establishing quick preventive measures to prevent the spread of KPC in hospitals.

키워드

참고문헌

  1. Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. PT. 2015;40:277-283.
  2. Sengupta S, Chattopadhyay MK, Grossart HP. The multifaceted roles of antibiotics and antibiotic resistance in nature. Front Microbiol. 2013;4:47. https://doi.org/10.3389/fmicb.2013.00047
  3. Centers for Disease Control and Prevention. Office of infectious disease antibiotic resistance threats in the United States, 2013 [Internet]. Atlanta: Centers for Disease Control and Prevention; 2015 [cited 2019 August 28]. Available from: https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf.
  4. Kim JE. Carbapenem-resistant Enterobacteriaceae in Korea. Hanyang Med Rev. 2018;38:99-102. https://doi.org/10.7599/hmr.2018.38.2.99
  5. Centers for Disease Control and Prevention. FAQs about choosing and implementing a CRE definition [Internet]. Atlanta: Centers for Disease Control and Prevention; 2015 [cited 2019 August 28]. Available from: https://www.cdc.gov/hai/organisms/cre/definition.html.
  6. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18:318-327. https://doi.org/10.1016/S1473-3099(17)30753-3
  7. McCann E, Srinivasan A, DeRyke CA, DePestel DD, Murray J, Gupta V. Carbapenem-nonsusceptible gram-negative pathogens in ICU and non-ICU settings in US hospitals in 2017: a multicenter study. Open Forum Infect Dis. 2018;5:ofy241. https://doi.org/10.1093/ofid/ofy241
  8. Potter RF, D'Souza AW, Dantas G. The rapid spread of carbapenem-resistant Enterobacteriaceae. Drug Resist Updat. 2016;29:30-46. https://doi.org/10.1016/j.drup.2016.09.002
  9. Iovleva A, Doi Y. Carbapenem-resistant Enterobacteriaceae. Clin Lab Med. 2017;37:303-315. https://doi.org/10.1016/j.cll.2017.01.005
  10. Lee HJ, Lee DG. Carbapenem-resistant Enterobacteriaceae: recent updates and treatment strategies. J Korean Med Assoc. 2018;61:281-289. https://doi.org/10.5124/jkma.2018.61.4.281
  11. Tamma PD, Goodman KE, Harris AD, Tekle T, Roberts A, Taiwo A, et al. Comparing the outcomes of patients with carbapenemase-producing and non-carbapenemase producing carbapenem- resistant Enterobacteriaceae bacteremia. Clin Infect Dis. 2017;64:257-264. https://doi.org/10.1093/cid/ciw741
  12. Falagas ME, Tansarli GS, Karageorgopoulos DE, Vardakas KZ. Deaths attributable to carbapenem-resistant Enterobacteriaceae infections. Emerg Infect Dis. 2014;20:1170-1175. https://doi.org/10.3201/eid2007.121004
  13. Hauck C, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, et al. Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections. Clin Microbiol Infect. 2016;22:513-519. https://doi.org/10.1016/j.cmi.2016.01.023
  14. Goodman KE, Simner PJ, Tamma PD, Milstone AM. Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE). Expert Rev Anti Infect Ther. 2016;14:95-108. https://doi.org/10.1586/14787210.2016.1106940
  15. Aires-de-Sousa M, Ortiz de la Rosa JM, Goncalves ML, Pereira AL, Nordmann P, Poirel L. Epidemiology of carbapenemase-producing Klebsiella pneumoniae in a hospital, Portugal. Emerg Infect Dis. 2019;25:1632-1638. https://doi.org/10.3201/eid2509.190656
  16. van Duin D, Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence. 2017;8:460-469. https://doi.org/10.1080/21505594.2016.1222343
  17. Korea Centers for Disease Control and Prevention. 2017 Guidelines for management of medical-related infectious diseases (VRSA/CRE) [Internet]. Cheongju: Korea Centers for Disease Control and Prevention; 2017 [cited 2019 August 28]. Available from: http://www.cdc.go.kr/board.es?mid=a20507020000&bid=0019&act=view&list_no=138074.
  18. Jeong SH, Kim HS, Kim JS, Shin DH, Kim HS, Park MJ, et al. Prevalence and molecular characteristics of carbapenemase-producing Enterobacteriaceae from five hospitals in Korea. Ann Lab Med. 2016;36:529-535. https://doi.org/10.3343/alm.2016.36.6.529
  19. Ahn SY, Sung JY, Kim HS, Kim MS, Hwang YJ, Jong SR, et al. Molecular epidemiology and characterization of carbapenemase-producing Enterobacteriaceae isolated at a university hospital in Korea during 4-year period. Ann Clin Microbiol. 2016;19:39-47. https://doi.org/10.5145/ACM.2016.19.2.39
  20. Lodise TP, Bonine NG, Ye JM, Folse HJ, Gillard P. Development of a bedside tool to predict the probability of drug-resistant pathogens among hospitalized adult patients with gram-negative infections. BMC Infectious Diseases. 2019;19:718. https://doi.org/10.1186/s12879-019-4363-y
  21. Gupta V, Ye G, Olesky M, Lawrence K, Murray J, Yu K. Trends in resistant Enterobacteriaceae and Acinetobacter species in hospitalized patients in the United States: 2013-2017. BMC Infect Dis. 2019;19:742. https://doi.org/10.1186/s12879-019-4387-3
  22. Clinical Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twenty-first informational supplement M100-S27. Wayne, PA: Clinical Laboratory Standards Institute; 2017.
  23. Bonomo RA, Burd EM, Conly J, Limbago BM, Poirel L, Segre JA, et al. Carbapenemase-producing organisms: a global scourge. Clin Infect Dis. 2018;66:1290-1297. https://doi.org/10.1093/cid/cix893
  24. Bora A, Sanjana R, Jha BK, Mahaseth SN, Pokharel K. Incidence of metallo-beta-lactamase producing clinical isolates of Escherichia coli and Klebsiella pneumoniae in central Nepal. BMC Res Notes. 2014;7:557. https://doi.org/10.1186/1756-0500-7-557
  25. Monteiro J, Widen RH, Pignatari ACC, Kubasek C, Silbert S. Rapid detection of carbapenemase genes by multiplex real-time PCR. J Antimicrob Chemother. 2012;67:906-909. https://doi.org/10.1093/jac/dkr563
  26. Doyle D, Peirano G, Lascols C, Lloyd T, Church DL, Pitout JD. Laboratory detection of Enterobacteriaceae that produce carbapenemases. J Clin Microbiol. 2012;50:3877-3880. https://doi.org/10.1128/JCM.02117-12
  27. Rhee JY, Park YK, Shin JY, Choi JY, Lee MY, Peck KR, et al. 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. 2010;54:2278-2279. https://doi.org/10.1128/AAC.00011-10
  28. Bae IK, Kang HK, Jang IH, Lee W, Kim K, Kim JO, et al. Detection of carbapenemases in clinical Enterobacteriaceae isolates using the VITEK AST-N202 card. Infect Chemother. 2015;47:167-174. https://doi.org/10.3947/ic.2015.47.3.167
  29. Roh KH, Lee CK, Sohn JW, Song W, Yong D, Lee K. Isolation of a Klebsiella pneumoniae isolate of sequence type 258 producing KPC-2 carbapenemase in Korea. Korean J Lab Med. 2011;31:298-301. https://doi.org/10.3343/kjlm.2011.31.4.298
  30. Jeong SH, Lee KM, Lee J, Bae IK, Kim JS, Kim HS, et al. Clonal and horizontal spread of the bla OXA-232 gene among Enterobacteriaceae in a Korean hospital. Diagn Microbiol Infect Dis. 2015;82:70-72. https://doi.org/10.1016/j.diagmicrobio.2015.02.001
  31. Garg A, Garg J, Kumar S, Bhattacharya A, Agarwal S, Upadhyay GC. Molecular epidemiology & therapeutic options of carbapenem-resistant gram-negative bacteria. Indian J Med Res. 2019;149:285-289. https://doi.org/10.4103/ijmr.IJMR_36_18
  32. Centers for Disease Control and Prevention. Patients with NDM-producing carbapenem-resistant Enterobacteriaceae (CRE) reported to the Centers for Disease Control and Prevention (CDC) as of December 2017, by state [Internet]. Atlanta: Centers for Disease Control and Prevention; 2017 [cited 2019August 28]. Available from: https://www.cdc.gov/hai/organisms/cre/trackingcre.html.
  33. Rodriguez-Bano J, Gutierrez-Gutierrez B, Machuca I, Pascual A. Treatment of infections caused by extended-spectrum- beta-lactamase-, AmpC-, and carbapenemase-producing Enterobacteriaceae. Clin Microbiol Rev. 2018;31:1-42. https://doi.org/10.1128/CMR.00079-17
  34. Park JW, Lee EJ, et al. Status of carbapenemase producing Enterobacteriaceae incidences in Korea, 2015-2016. Research report. Cheongju: Korea Centers for Disease Control and Prevention; 2017;10:1243-1247.
  35. Go EB, Ju SJ, et al. Distribution of carbapenem-resistant Enterobacteriaceae (CRE) in Korea, 2017. Research report. Cheongju: Korea Centers for Disease Control and Prevention; 2018;11:1518-1522.
  36. Weiner LM, Webb AK, Limbago B, Dudeck MA, Patel J, Kallen AJ, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the national healthcare safety network at the Centers for Disease Control and Prevention, 2011-2014. Infect Control Hosp Epidemiol. 2016;37:1288-1301. https://doi.org/ 10.1017/ice.2016.174