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그람 음성 간균에서 16S rRNA Methylase 생성 빈도와 생성 세균의 내성 양상

Molecular and Phenotypic Characteristics of 16S rRNA Methylase-producing Gram-negative Bacilli

김창기|고은미|이경원|이혁민|정윤섭|염종화
대한임상미생물학회 (Korean Society of Clinical Microbiology)|2010.03|Annals of Clinical Microbiology|제13권 제1호|pp. 19-26

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키워드

armA16S rRNA dimethylaseqnrBAminoglycosideGram-negative bacilli

초록

배경: 근래에 16S rRNA를 methylation하여 임상적으로 유용한 모든 aminoglycoside 항균제에 고도 내성을 보이는 새로운내성 기전이 보고되었으나, 이에 대한 국내 연구는 드물다. 이에 본 연구에서는 서울과 경기도에 소재하는 2차와 3차병원의 환자에서 분리되는 그람음성 간균 중에서 16S rRNA methylase를 생성하는 균주의 빈도와 그 내성 유전형 및 다제내성 양상을 규명하고자 하였다. 방법: 2006년 7월∼2007년 6월에 경기도의 2차 병원과 2007년 4∼6월에 서울의 3차 병원에 내원한 환자에서 분리한 일련의 그람 음성 간균을 대상으로 하였으며, 중복 분리주는 제외하였다. 수집한 균주는 한천 희석법으로 항균제 감수성을시험하였고, 16S rRNA methylase 생성은 arbekacin 디스크를 이용하여 선별한 후, PCR로 유전자를 검출하였다. 결과: 그람음성 간균 중, 16S rRNA methylase 양성 균주의 비율은 2차 병원 5% (75/1,471) 및 3차 병원 4% (48/1,251)였으며, Escherichia coli 1% (10/1,062), Klebsiella pneumoniae 16% (75/460), K. oxytoca 2% (1/44), Citrobacter spp. 9% (7/82),Enterobacter spp. 2% (4/181), Serratia marcescens 6% (6/100), Proteus miriabilis 4% (2/57), Achromobacter xylosoxidans 20%(1/5), Pseudomonas aeruginosa ＜1% (1/505), Acinetobacter spp. 10% (11/112) 및 Stenotrophomonas maltophilia 2% (1/66)에서 확인되었다. armA는 3차 병원 분리주 48주 중 43주(90%)에서, 2차 병원 분리주 75주 중 70주(93%)에서 양성이었으며,1주를(rmtA) 제외한 나머지 균주는 rmtB 양성이었다. 16S rRNA methylase 생성 K. pneumoniae의 ESBL 양성률 및 cefoxtin 내성률은 59% (44/75) 및 92% (69/75)로 높았으며, 특히 16S rRNA methylase 양성 K. pneumoniae의 91%가 qnrB를 동시에가지고 있었다. 16S rRNA methylase 양성인 Pseudomonas 및 Acinetobacter 균종에서 metallo-β-lactamase를 생성하는 균주는 없었다. 결론: 국내에서 16S rRNA methylase 유전자 양성인 그람음성 간균은 외국에 비하여 흔하였고, 여러 균종에 널리 퍼져있으며, 다제 내성인 경우가 많았다. [대한임상미생물학회지 2010;13:19-26]

Abstract

Background: Recently a novel plasmid-mediated resistant mechanism that conferred high-level resistance to aminoglycoside via methylation of 16S rRNA was reported. The aims of this study were to determine the prevalence of the 16S rRNA methylase genes and to characterize the coresistance to other antibiotics in Gram-negative bacilli. Methods: Consecutive non-duplicate Gram-negative bacilli were isolated from clinical specimens at a Korean secondary- and tertiary-care hospital from July 2006to June 2007. The antimicrobial susceptibility was tested by the CLSI agar dilution method,and PCR was performed to detect the 16S rRNA methylase genes in the arbekacin-resistant isolates. Results: In Gram-negative bacilli, the proportions of 16S rRNA methylase gene-positive isolates were 5%(75/1,471) in the secondary-carehospital and 4%(48/1,251) in the tertiary-care hospital, and the positive rates by species were 1% Escherichiae coli 16% (10/1,062), Klebsiella pneumoniae 16% (75/460), K. oxytoca 2% (1/44), Citrobacter spp. 9% (7/82), Enterobacter spp. 2% (4/181), Serratia marcescens 6% (6/100), Proteus miriabilis 4% (2/57), Achromobacter xylosoxidans 20% (1/5), Pseudomonas aeruginosa ＜1% (1/505), Acinetobacter spp. 10% (11/112), and Stenotrophomonas maltophilia 2% (1/66),respectively. Among 16S rRNA methylase-positive isolates from secondary- and tertiary-care hospitals,93% (70/75) and 90% (43/48), respectively, were armA positive, and others, except one rmtA positive isolate, were positive for the rmtB gene, according to PCR results. The rates of ESBL-positive and cefoxitin-resistant K. pneumoniae were 59% and 92%,respectively. In addition, 91% of 16S rRNA methylase-producing K. pneumoniae were positive for qnrB. There were no MBL producers among 16S rRNA methylase-producing Pseudomonas and Acinetobacter species. Conclusion: The novel aminoglycoside-resistant mechanisms involving16S rRNA methylase were prevalent and widely distributed among Gram-negative bacilli in Korea, and other resistance mechanisms were commonly associated with 16S rRNA methylasemediated resistance in Korea. (Korean J Clin Microbiol 2010;13:19-26)

참고문헌 (30)

  1. 이경원, "Further Increase of Vancomycin-Resistant Enterococcus faecium, Amikacin- and Fluoroquinolone-Resistant Klebsiella pneumoniae, and Imipenem-Resistant Acinetobacter spp. in Korea", Yonsei Medical Journal, 47(1), pp.43~54 (2006), 연세대학교의과대학
  2. Vakulenko SB, "Versatility of aminoglycosides and prospects for their future", Clin Microbiol Rev, 16, pp.430~450 (2003)
  3. Galimand M, "Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation", Antimicrob Agents Chemother, 47, pp.2565~2571 (2003)
  4. Yokoyama K, "Acquisition of 16S rRNA methylase gene in Pseudomonas aeruginosa", Lancet, 362, pp.1888~1893 (2003)
  5. Doi Y, "Plasmid-mediated 16S rRNA methylase in Serratia marcescens conferring high-level resistance to aminoglycosides", Antimicrob Agents Chemother, 48, pp.491~496 (2004)
  6. Wachino J, "Novel plasmid-mediated 16S rRNA methylase, RmtC, found in a Proteus mirabilis isolate demonstrating extraordinary high-level resistance against various aminoglycosides", Antimicrob Agents Chemother, 50, pp.178~184 (2006)
  7. Doi Y, "Coproduction of novel 16S rRNA methylase RmtD and metallo-beta-lactamase SPM-1 in a panresistant Pseudomonas aeruginosa isolate from Brazil", Antimicrob Agents Chemother, 51, pp.852~856 (2007)
  8. Yan JJ, "Plasmid-mediated 16S rRNA methylases conferring high-level aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae isolates from two Taiwanese hospitals", J Antimicrob Chemother, 54, pp.1007~1012 (2004)
  9. Lee H, "Dissemination of 16S rRNA methylase-mediated highly amikacinresistant isolates of Klebsiella pneumoniae and Acinetobacter baumannii in Korea", Diagn Microbiol Infect Dis, 56, pp.305~312 (2006)
  10. Kondo S, "Development of arbekacin and synthesis of new derivatives stable to enzymatic modifications by methicillinresistant Staphylococcus aureus", Jpn J Antibiot, 47, pp.561~574 (1994)
  11. Clinical and Laboratory Standards Institute, "Performance standards for antimicrobial susceptibility testing; Seventeenth informational supplement" (2006), CLSI
  12. Cattoir V, "Multiplex PCR for detection of plasmid-mediated quinolone resistance qnr genes in ESBL-producing enterobacterial isolates", J Antimicrob Chemother, 60, pp.394~397 (2007)
  13. Skeggs PA, "Methylation of 16S ribosomal RNA and resistance to aminoglycoside antibiotics in clones of Streptomyces lividans carrying DNA from Streptomyces tenjimariensis", Mol Gen Genet, 200, pp.415~421 (1985)
  14. Cundliffe E, "How antibiotic-producing organisms avoid suicide", Annu Rev Microbiol, 43, pp.207~233 (1989)
  15. Bogaerts P, "Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in Belgium", J Antimicrob Chemother, 59, pp.459~464 (2007)
  16. Yamane K, "16S rRNA methylase-producing, gram-negative pathogens", Japan. Emerg Infect Dis, 13, pp.642~646 (2007)
  17. Park YJ, "Co-production of 16S rRNA methylases and extended-spectrum beta-lactamases in AmpC-producing Enterobacter cloacae, Citrobacter freundii and Serratia marcescens in Korea", J Antimicrob Chemother, 58, pp.907~908 (2006)
  18. Chen L, "Emergence of RmtB methylase-producing Escherichia coli and Enterobacter cloacae isolates from pigs in China", J Antimicrob Chemother, 59, pp.880~885 (2007)
  19. Galimand M, "Worldwide disseminated armA aminoglycoside resistance methylase gene is borne by composite transposon Tn1548", Antimicrob Agents Chemother, 49, pp.2949~2953 (2005)
  20. Golebiewski M, "Complete nucleotide sequence of the pCTX-M3 plasmid and its involvement in spread of the extended- spectrum β-lactamase (ESBL) gene blaCTX-M-3", Antimicrob Agents Chemother (2007)
  21. 배일권, "CTX-M-12, PER-1 및 OXA-30 β-Lactamase 생성 Klebsiella pneumoniae의 출현", 대한임상미생물학회지, 9(2), pp.102~109 (2006), 대한임상미생물학회
  22. Yu YS, "Widespread occurrence of aminoglycoside resistance due to ArmA methylase in imipenem- resistant Acinetobacter baumannii isolates in China", J Antimicrob Chemother, 60, pp.454~455 (2007)
  23. Doi Y, "Identification of 16S Ribosomal RNA Methylase-Producing Acinetobacter baumannii Clinical Strains in North America", Antimicrob Agents Chemother, 51, pp.4209~4210 (2007)
  24. Doi Y, "High prevalence of metallo-beta-lactamase and 16S rRNA methylase coproduction among imipenem-resistant Pseudomonas aeruginosa isolates in Brazil", Antimicrob Agents Chemother, 51, pp.3388~3390 (2007)
  25. Hooper DC, "Mechanisms of Quinolone Resistance in Quinolone Antimicrobial Agents. 3rd ed", pp.41~67 (2003), American Society for Microbiology Press
  26. Poole K, "Efflux pumps as antimicrobial resistance mechanisms", Ann Med, 39, pp.162~176 (2007)
  27. Ruiz J, "Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection", J Antimicrob Chemother, 51, pp.1109~1117 (2003)
  28. Martinez-Martinez L, "Quionolone resistance from a transferable plasmid", Lancet, 351, pp.797~799 (1998)
  29. Yamane K, "New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate", Antimicrob Agents Chemother, 51, pp.3354~3360 (2007)
  30. Robicsek A, "The worldwide emergence of plasmid-mediated quinolone resistance", Lancet Infect Dis, 6, pp.629~640 (2006)

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