Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
권호 표지

Coproduction of qnrB and armA from Extended-Spectrum ${\beta}$-lactamase-producing Klebsiella pneumoniae

Extended-Spectrum ${\beta}$-lactamase를 생성하는 Klebsiella pneumoniae에서의 qnrB와 armA 유전자의 동시생성

Kim, Moon-Hee;Sung, Ji-Youn;Park, Jong-Woo;Kwon, Gye-Cheol;Koo, Sun-Hoe
김문희;성지연;박종우;권계철;구선회

  • Published : 2007.12.31
⟨ Previous Next ⟩

Abstract

Background : Multidrug-resistant Enterobacteriaceae is a worldwide problem. Although various resistance mechanisms have been recognized with increasing frequency, only a few cases of triple resistance of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae have been reported. This study was designed to evaluate the coexistence of qnr (qnrA, qnrB, and qnrS) and 16S rRNA methylase (armA, rmtA, rmtB, and rmtC) in ESBL-producing K. pneumoniae. Methods : We tested 44 isolates of ESBL-producing K. pneumoniae at Chungnam National University Hospital from March to September 2006. Antimicrobial susceptibilities were tested by broth microdilution method, and transconjugation test was performed using E. coli J53 with azide resistance. Search for qnr (qnrA, qnrB, and qnrS) and 16S rRNA methylase (armA, rmtA, rmtB, and rmtC) genes was conducted by PCR amplification, and the genotypes were determined by direct nucleotide sequence analysis of the amplified products. Epidemiologic study was performed by Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). Results : All ESBL-positive strains produced qnrB; however, armA was detected in 68.2%. The coproduction rate of qnrB and armA in ESBL-producing K. pneumoniae was 68.2%. Two types (A and B) were dominant in ERIC-PCR results. Conclusions : K. pneumoniae producing qnrB, armA, and ESBL are spreading widely.

배경 : 전세계적으로 다제 내성 장내 세균이 문제로 대두되고 있고 여러 가지 항균제에 대한 내성률이 증가하고 있으나 extended-spectrum β-lactamase (ESBL) 생성 Klebsiella pneumoniae에서의 ESBL, quinolone 및 aminoglycoside 제제에 대한 삼중 내성에 대한 보고가 없다. 이에 ESBL 생성 K. pneumoniae에서의 quinolone 및 aminoglycoside 제제에 대한 다제 내성 빈도를 알아보고자 하였다. 방법 : 2006년 3월부터 9월까지 충남대학교병원에서 분리된 ESBL유전형을 가진 K. pneumoniae 44주를 대상으로 β-lactam 항생제의 최소 억제 농도를 액체 배지 미량 희석법으로 측정하였다. Azide에 내성을 갖는 E. coli J53을 이용하여 피전달접합균주에 대한 시험을 하였다. PCR을 시행하였고 그 증폭 산물로 직접 염기 서열 분석을 시행하여 quinolone 및 aminoglycoside 제제에 대한 내성 유전형을 결정하였다. 역학연구는 Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR)로 하였다. 결과 : ESBL생성 K. pneumoniae 균주에서 qnrB 유전자는 100%에서, armA 유전자는 68.2%에서 검출되었고 따라서 3가지 유전자가 모두 검출된 균주는 68.2%였다. ERIC-PCR 결과 A, B형 두 가지가 우세하게 많았다. 결론 : qnrB, armA와 ESBL을 생성하는 K. pneumoniae가 널리 퍼져 있다.

Keywords

References

  1. Abbott S. Klebsiella, Enterobacter, Citrobacter and Serratia. In: Murray PR, Baron EJ, et al, eds. Manual of Clinical Microbiology. 7th ed. Washington: ASM press, 1999:475-82
  2. Podschum R and Ullman U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 1998;11:589-603
  3. Lee YH, Cho B, Bae IK, Chang CL, Jeong SH. Klebsiella pneumoniae strains carrying the chromosomal SHV-11 $\beta$-lactamase more frequently than those carrying the chromosomal SHV-1 $\beta$-lactamase gene. J Antimicrob Chemother 2006;57:1259-61 https://doi.org/10.1093/jac/dkl115
  4. Quitilaiani R Jr, Sahm DF, et al. eds. Mechanisms of resistance to antimicrobial agents. In: Murray PR, Baron EJ, et al. eds. Manual of Clinical Microbiology. 7th ed. Washington:ASM press 1999;1505-25
  5. Shin KS and Son BR. Comparison of Vitek ESBL test and other methods for detecting extended-spectrum $\beta$-lactamase producing Escherichia coli and Klebsiella species. Korean J Clin Pathol 2002;22: 21-6. (신경섭및손보라. Escherichia coli와 Klebsiella species에서 Extended- spectrum $\beta$-lactamase 검출을위한 Vitel ESBL test와그외방법의 비교. 대한임상병리학회지 2002;22:21-6.)
  6. Hong SG, Kang MS, Choi JR, Lee KW, Chong YS, Kwon OH. Molecular characteristics of extended-spectrum $\beta$-lactamases in clinical isolates of enterobacteriaceae. Korean J Clin Pathol 2001;21:495-504. (홍성근, 강명서, 최종락, 이경원, 정윤섭, 권오헌. 임상검체에서 분리된 Enterobacteriaceae 균종의 Extended-spectrum $\beta$-lactamase 유형및 분자역학적특성. 대한임상병리학회지 2001;21:495-504.)
  7. Lee BY, Jeong SH, Jeong TS, Nam HJ, Ji JH, Hong YR. Detection of extended-spectrum $\beta$-lactamase-producing Escherichia coli and Klebsiella spp. with the Vitek GNS 121 card. Korean J Clin Pathol 2001; 21:350-4. (이보영, 정석훈, 정태식, 남희준, 지종현, 홍유라. Vitek GNS 121 Card를이용한 Extended-spectrum $\beta$-Lactamase 생성 Escherichia coli와 Klebsiella spp. 검출. 대한임상병리학회지2001;21:350-4.)
  8. Lautenbach E, Strom BL, Nachamkin I, Bilker WB, Marr AM, Larosa LA, et al. Longitudinal trends in fluoroquinolone resistance among Enterobacteriacae isolates from inpatients and outpatients, 1989- 2000: differences in the emergence and epidemiology of resistance across organisms. Clin Infect Dis 2004;38:655-62 https://doi.org/10.1086/381549
  9. Jacoby GA, Chow N, Waites KB. Prevalence of plasmid-mediated quinolone resistance. Antimicrob Agents Chemother 2003;47:559-62 https://doi.org/10.1128/AAC.47.2.559-562.2003
  10. Wang M, Sahm DF, Jacoby GA, Hooper DC. Emerging plasmidmediated quinolone resistance associated with qnr gene in Klebsiella pneumoniae clinical isolates in the United States. Antimicrob Agents Chemother 2004;48:1295-9 https://doi.org/10.1128/AAC.48.4.1295-1299.2004
  11. Itokazu GS, Quinn JP, Bell-Dixon C, Kahan FM, Weinstein RA. Antimicrobial resistance rates among aerobic gram-negative bacilli recovered from patients in intensive care units: evaluation of a national postmarketing surveillance program. Clin Infect Dis 1996;23:779-84 https://doi.org/10.1093/clinids/23.4.779
  12. Lautenbach E, Strom BL, Bilker WB, Patel JB, Edelstein PH, Fishman NO. Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum $\beta$-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Clin Infect Dis 2001;33: 1288-94 https://doi.org/10.1086/322667
  13. Paterson DL, Mulazimoglu L, Casellas JM, Ko WC, Goossens H, Von Gottberg A, et al. Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum $\beta$-lactamase production in Klebsiella pneumoniae isolates causing bacteremia. Clin Infect Dis 2000; 30:473-8 https://doi.org/10.1086/313719
  14. Kotra LP, Haddad J, Mobashery S. Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicorb Agents Chemother 2000;44:3249-56 https://doi.org/10.1128/AAC.44.12.3249-3256.2000
  15. Galimand M, Courvalin P, Lambert T. Plasmid-mediated high level resistance to aminoglycosides in Enterobacteriaceae due to 16s rRNA methylation. Antimicrob Agents Chemother 2003;47:2565-71 https://doi.org/10.1128/AAC.47.8.2565-2571.2003
  16. Galimand M, Sabtcheva S, Courvalin P, Lambert T. Worldwide disseminated armA aminoglycoside resistance methlyase gene is borne by composite transposon Tn1548. Antimicrob Agents Chemother 2005;49:2949-53 https://doi.org/10.1128/AAC.49.7.2949-2953.2005
  17. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; sixteenth informational supplement. M100-S16. Wayne, Pensylvania: CLSI, 2006
  18. Jacoby GA and Han P. Detection of extended-spectrum beta-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli. J Clin Microbiol 1996;34:908-11
  19. Versalovic J, Koeuth T, Lupski JR. Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. Nucleic Acids Res 1999;19:6823?31
  20. Livermore DM. $\beta$-Lactamases in laboratory and clinical?resistance. Clin Microbioal Rev 1995;8:557-84
  21. Hong SG, Kim SJ, Jeong SH, Chang CH, Cho SR, Ahn JY, et al. Prevalence and diversity of extened-spectrum $\beta$-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates in Korea. Korean J Clin Microbiol 2003;6:149-55. (홍성근, 김선주, 정석훈, 장철훈, 조성란, 안지영 등. 국내에서 분리된 Extended-spectrum $\beta$-lactamase 생성 Escherichia coli and Klebsiella pneumoniae의 빈도 및 유형. 대한임상미생물학회지 2003;6:149-55.)
  22. Wang M, Tran JH, Jacoby GA, Zhang Y, Wang F, Hooper DC. Plasmid- mediated quinolone resistance in clinical isolates of Escherichia coli from Shanghai, China. Antimicrob Agents Chemother 2003;47: 2242-8 https://doi.org/10.1128/AAC.47.7.2242-2248.2003
  23. Bogaerts P, Galimand M, Baurang C, Deplano A, Vanhoof R, De Mendonca R, et al. Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in Belgium. J Antimicrob Chemother 2007;59:459-64 https://doi.org/10.1093/jac/dkl527
  24. Martinez-Martinez L, Pascual A, Garcia I, Tran J, Jacoby GA. Interaction of plasmid and host quinolone resistance. J Antimicrob Chemother 2003;51:1037-9 https://doi.org/10.1093/jac/dkg157
  25. Yan JJ, Wu JJ, Ko WC, Tsai SH, Chuang CL, Wu HM, et al. Plasmidmediated 16S rRNA methylase conferring high-level aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae isolates from two Taiwanese hospitals. J Antimicrobial Chemother 2004;54: 1007-12 https://doi.org/10.1093/jac/dkh455
  26. Lee H, Yong D, Yum JH, Roh KH, Lee K, Yamane K, et al. Dissemination of 16S rRNA methylase-mediated highly amikacin-resistant isolates of Klebsiella pneumoniae and Acinetobacter baumannii in Korea. Diagn Microbiol Infect Dis 2006;56:305-12 https://doi.org/10.1016/j.diagmicrobio.2006.05.002
  27. Lee K, Lee M, Shin JH, Lee MH, Kang SH, Park AJ, et al. Prevalence of plasmid-mediated AmpC $\beta$-lactamases in Escherichia coli and Klebsiella pneumoniae in Korea. Microb Drug Resist 2006;12:44-9 https://doi.org/10.1089/mdr.2006.12.44
  28. Kang JH, Bae IK, Kwon SB, Jeong SH, Lee JW, Lee WG, et al. Prevalence of Ambler Class A extended-spectrum $\beta$-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates in Korea. Korean J Clin Microbiol 2005;8:17-25. (강지혜, 배일권, 권수봉, 정석훈, 이종 욱, 이위교등. Ambler Class A Extended-Spectrum $\beta$-Lactamase 생 성 Escherichia coli와 Klebsiella pneumoniae의국내분리현황. 대한임상미생물학회지 2005;8:17-25.)
  29. Cattoir V, Weill FX, Poirel L, Fabre L, Soussy CJ, Nordmann P. Prevalence of qnr genes in Salmonella in France. J Antimicrob Chemother 2007;59:751-4 https://doi.org/10.1093/jac/dkl547
  30. Park YJ, Lee S, Yu JK, Woo GJ, Lee K, Arakawa Y. 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 2006;58:907-8 https://doi.org/10.1093/jac/dkl317