대한임상검사과학회지 (Korean Journal of Clinical Laboratory Science)

  • 제49권4호
  • /
  • Pages.427-434
  • /
  • 2017
  • /
  • 1738-3544(pISSN)
  • /
  • 2288-1662(eISSN)
대한임상검사과학회 (Korean Society for Clinical Laboratory Science)
권호 표지
DOI QR코드

DOI QR Code

충청지역의 임상검체로부터 분리된 Acinetobacter calcoaceticus-baumannii Complex를 대상으로 항균제 내성 유전자 비교분석

Distribution of Antimicrobial Resistant Genes in Acinetobacter calcoaceticus-baumannii Complex Isolated from Clinical Specimens in Chungcheong, Korea

  • 성지연 (극동대학교 임상병리학과)
  • Sung, Ji Youn (Department of Biomedical Laboratory Science, Far East University)
  • 투고 : 2017.09.06
  • 심사 : 2017.10.11
  • 발행 : 2017.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Acinetobacter calcoaceticus-baumannii (Acb) complex에 속한 종들은 빈번하게 병원감염 및 기회감염을 일으킨다. 또한 다제내성인 경우가 많아 이 균들의 감염증 치료를 위한 항균제 선택이 매우 제한적이다. 본 연구에서는 ciprofloxacin 내성 Acinetobacter species 53균주를 대상으로 fluoroquinolone 내성기전을 조사했다. 항균제 감수성 양상을 조사하기 위해 디스크확산법이 시행되었다. Fluoroquinolone 내성과 관련된 유전자 및 돌연변이 검출을 위해 PCR과 염기서열분석이 이루어졌다. 본 연구에서 수집된 53균주의 ciprofloxacin 내성 Acinetobacter 중 47균주가 gyrA 유전자의 83번째 serine 아미노산 잔기와 parC 유전자의 80번째 serine 아미노산 잔기가 leucine 잔기로 치환된 sense mutations 가지고 있는 것으로 나타났다. gyrA와 parC 유전자에 sense mutations을 가지고 있는 47균주 중 44균주가 A. baumannii 였고 3균주는 A. pittii였다. 본 연구에서 조사대상이 되었던 Acb complex 균주들 중 plasmid-mediated quinolone resistance (PMQR) determinants를 가지고 있는 균주는 한나도 없었다. 46 균주의 ciprofloxacin 내성 A. baumannii 는 A, B, 또는 F형의 banding pattern을 보였는데 이는 충청지역에 위치한 일개의 병원에 ciprofloxacin 내성 A. baumannii가 수평확산 되어 있음을 의미한다. Fluoroquinolone 내성 Acb complex 균주의 집락화 및 확산을 막기 위해서 다제내성 균주들을 대상으로 항균제 내성인자들을 지속적으로 조사하고 모니터링할 필요가 있을 것으로 사료된다.

Species that belong to the Acinetobacter calcoaceticus-baumannii (Acb) complex are major causes of hospital-acquired infections. They are important opportunistic pathogens. These species are usually multidrug resistant (MDR), and the therapeutic options to treat the infections caused by these species are limited. In the present study, we investigated fluoroquinolone resistance mechanisms in 53 ciprofloxacin resistant Acinetobacter species isolates in Chungcheong, Korea. Antimicrobial susceptibilities were determined using the disk-diffusion method. Detections of genes and identification of mutations associated with fluoroquinolone resistance were carried out using PCR and DNA sequencing. In our study, 47 out of 53 ciprofloxacin resistant Acinetobacter isolates harbored sense mutations at the 83rd residue (serine to leucine) in the gyrA gene as well as at the 80th residue (serine to leucine) in the parC gene. Among the 47 isolates harboring sense mutations in gyrA and parC gene, 44 isolates were A. baumannii and 3 isolates were A. pittii. Plasmid-mediated quinolone resistance (PMQR) determinants were detected in isolates in our study. Among the 46 ciprofloxacin resistant A. baumannii isolates, 41 showed type A, B, or F banding patterns on their REP-PCR profiles. This result suggests that clonal relation and horizontal spreading of the bacterial isolates have been around hospitals in Chungcheong area. To prevent colonization and disseminations of fluoroquinolone resistance Acb complex isolates, continuous investigation and monitoring of antimicrobial resistant determinants of MDR isolates are needed.

키워드

참고문헌

  1. Sung JY. Clonal dissemination of multidrug resistant Acinetobacter baumannii isolates harboring blaOXA-23 at One University Hospital in Daejeon, Korea. Korean J Clin Lab Sci. 2016;48(2):94-101. https://doi.org/10.15324/kjcls.2016.48.2.94
  2. La Scola B, Gundi VA, Khamis A, Raoult D. Sequencing of the rpoB gene and flanking spacers for molecular identification of Acinetobacter species. J Clin Microbiol. 2006;44(3):827-832. https://doi.org/10.1128/JCM.44.3.827-832.2006
  3. Srinivasan VB, Rajamohan G, Pancholi P, Stevenson K, Tadesse D, Patchanee P, et al. Genetic relatedness and molecular characterization of multidrug resistant Acinetobacter baumannii isolated in central Ohio, USA. Ann Clin Microbiol Antimicrob. 2009;8:21-22. https://doi.org/10.1186/1476-0711-8-21
  4. Vila J, Ruiz J, Goni P, Jimenez de Anta T. Quinolone-resistance mutations in the topoisomerase IV parC gene of Acinetobacter baumannii. J Antimicrob Chemother. 1997;39(6):757-762. https://doi.org/10.1093/jac/39.6.757
  5. Jacoby GA. Mechanisms of resistance to quinolones. Clin Infect Dis. 2005;41(Suppl 2):120-126. https://doi.org/10.1086/428052
  6. Nordmann P, Poirel L. Emergence of plasmid-mediated resistance to quinolones in Enterobacteriaceae. J Antimicrob Chemother. 2005;56(3):463-469. https://doi.org/10.1093/jac/dki245
  7. Jiang X, Yu T, Jiang X, Zhang W, Zhang L, Ma J. Emergence of plasmid-mediated quinolone resistance genes in clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa in Henan, China. Diagn Microbiol Infect Dis. 2014;79(3):381-383. https://doi.org/10.1016/j.diagmicrobio.2014.03.025
  8. Touati A, Brasme L, Benallaoua S, Gharout A, Madoux J, De Champs C. First report of qnrB-producing Enterobacter cloacae and qnrA-producing Acinetobacter baumannii recovered from Algerian hospitals. Diagn Microbiol Infect Dis. 2008; 60(3):287-290. https://doi.org/10.1016/j.diagmicrobio.2007.10.002
  9. Lim J, Lee G, Choi Y, Kim J. An analysis of the antibiotic resistance genes of multi-drug resistant (MDR) Acinetobacter baumannii. Korean J Clin Lab Sci. 2016;48(3):217-224. https://doi.org/10.15324/kjcls.2016.48.3.217
  10. Bou G, Cervero G, Dominguez MA, Quereda C, Martinez-Beltran J. PCR-based DNA fingerprinting (REP-PCR, AP-PCR) and pulsed-field gel electrophoresis characterization of a nosocomial outbreak caused by imipenem- and meropenem-resistant Acinetobacter baumannii. Clin Microbiol Infect. 2000; 6(12):635-643. https://doi.org/10.1046/j.1469-0691.2000.00181.x
  11. CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Sixteenth Informational Supplement. CLSI document M100-S20. Wayne, Pennsylvania: Clinical and Laboratory Standards Institute; 2010, p52-53.
  12. Valentine SC, Contreras D, Tan S, Real LJ, Chu S, Xu HH. Phenotypic and molecular characterization of Acinetobacter baumannii clinical isolates from nosocomial outbreaks in Los Angeles County, California. J Clin Microbiol. 2008;46(8): 2499-2507. https://doi.org/10.1128/JCM.00367-08
  13. Cattoir V, Poirel L, Rdotimi V, Soussy CJ, Nordmann P. Multiplex PCR for detection of plasmid-mediated quinolone resistance qnr genes in ESBL-producing enterobacterial isolates. J Antimicrob Chemother. 2007;60(2):394-397. https://doi.org/10.1093/jac/dkm204
  14. Park CH, Robicsek A, Jacoby GA, Sahm D, Hooper DC. Prevalence in the United States of aac(6')-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob Agents Chemother. 2006;50(11):3953-3955. https://doi.org/10.1128/AAC.00915-06
  15. Li J, Wang T, Shao B, Shen J, Wang S, Wu Y. Plasmid-mediated quinolone resistance genes and antibiotic residues in wastewater and soil adjacent to swine feedlots: potential transfer to agricultural lands. Environ Health Perspect. 2012;120(8):1144-1149. https://doi.org/10.1289/ehp.1104776
  16. Khorsi K, Messai Y, Hamidi M, Ammari H, Bakour R. High prevalence of multidrug-resistance in Acinetobacter baumannii and dissemination of carbapenemase-encoding genes $bla_{OXA-23-lik}$, $bla_{OXA-24-like}$ and $bla_{NDM-1}$ in Algiers hospitals. Asian Pac J Trop Med. 2015;8(6):438-446. https://doi.org/10.1016/j.apjtm.2015.05.011
  17. Park YK, Jung SI, Park KH, Kim DH, Choi JY, Kim SH, et al. Changes in antimicrobial susceptibility and major clones of Acinetobacter calcoaceticus-baumannii complex isolates from a single hospital in Korea over 7 years. J Med Microbiol. 2012;61(Pt 1):71-79. https://doi.org/10.1099/jmm.0.033852-0
  18. Koo SH, Kwon KC, Cho HH, Sung JY. Genetic basis of multidrug-resistant Acinetobacter baumannii clinical isolates from three university hospitals in Chungcheong province, Korea. Korean J Lab Med. 2010;30(5):501-506.
  19. Valentine SC, Contreras D, Tan S, Real LJ, Chu S, Xu HH. Phenotypic and molecular characterization of Acinetobacter baumannii clinical isolates from nosocomial outbreaks in Los Angeles County, California. J Clin Microbiol. 2008;46(8):2499-2507. https://doi.org/10.1128/JCM.00367-08
  20. Guler G, Erac B. Investigation of fluoroquinolone resistance mechanisms in clinical Acinetobacter baumannii isolates. Mikrobiyol Bul. 2016;50(2):278-286. https://doi.org/10.5578/mb.24126
  21. Lee JK, Lee YS, Park YK, Kim BS. Mutations in the gyrA and parC genes in ciprofloxacin-resistant clinical isolates of Acinetobacter baumannii in Korea. Microbiol Immunol. 2005; 49(7):647-653. https://doi.org/10.1111/j.1348-0421.2005.tb03643.x
  22. Yang H, Hu L, Liu Y, Ye Y, Li J. Detection of the plasmid-mediated quinolone resistance determinants in clinical isolates of Acinetobacter baumannii in China. J Chemother. 2016;28(5): 443-445. https://doi.org/10.1179/1973947815Y.0000000017
  23. Gu DX, Hu YJ, Zhou HW, Zhang R, Chen GX. Substitutions of Ser83Leu in GyrA and Ser80Leu in ParC Associated with Quinolone Resistance in Acinetobacter pittii. Microb Drug Resist. 2015;21(3):345-351. https://doi.org/10.1089/mdr.2014.0057
  24. MJ Jiang, Sh P Zhao, J M Li, FS Zhang. Molecular epidemiological study and detection of multi-drug resistant Acinetobacter baumannii-related resistance genes. African J Mirobiol Reser. 2013;7(48):5496-5502. https://doi.org/10.5897/AJMR2013.6109