2006-2008년 국내 임상검체 및 동물에서 분리된 Non-Typhoidal Salmonella 균주에서의 Extended-Spectrum β-Lactamase, Plasmid-Mediated AmpC β-Lactamase와 Plasmid-Mediated Quinolone 내성 qnr 유전자의 빈도
A Korean Nationwide Surveillance Study for Non-Typhoidal Salmonella Isolated in Humans and Food Animals from 2006 to 2008: Extended-Spectrum β-Lactamase, Plasmid-Mediated AmpC β-Lactamase, and Plasmid-Mediated Quinolone Resistance qnr Genes
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배경: 침습성 비장티푸스성 살모넬라(non-typhoidal Salmonella, NTS) 감염에 사용되는 fluoroquinolone, ampicillin 및 ceftriaxone에 감수성이 저하된 균주가 세계적으로 출현하고 있으나 국내에서 이에 대한 연구는 제한되어 있다. 본 연구에서는 국내의 임상 및 비임상 검체에서 분리된 NTS의 항균제 내성 양상, 주요 내성 유전자의 분리 빈도와 분자역학적 분석을 시행하였다. 방법: 2006-2008년 질병관리본부와 국립 수의과학 검역원에서 임상 NTS 균주 219주 및 비임상검체 분리 NTS 균주 293주를 수집하였다. 항균제 감수성 시험은 Clinical and Laboratory Standards Institute 디스크 확산법으로 시행하였다. Extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC β-lactamase (PABL), 그리고 plasmid-mediated quinolone resistance는 항균제 내성형으로 선별하여 PCR, 염기서열 분석을 통하여 확인하였다. Pulsed-field gel electrophoresis를 이용하여 분자역학적 관계를 규명하였다. 결과: Ampicillin 내성률은 임상 균주에서 49%, 비임상 균주에서 18-47%이었다. 한편 1차 치료 약제인 trimethoprim-sulfamethoxazole 내성률은 임상 균주에서 8%, 비임상 균주에서 0-41%이었다. Extended-spectrum cephalosporin 내성률은 0-1%이었다. CTX-M-15형 ESBL 생성 균주 1주와 CMY-2형 PABL 생성 균주 4주를 검출하였다. 특히 비임상 분리균주 1주를 포함한 blaCMY-2형 유전자 양성인 S. Typhimurium 4주는 높은 유전적 연관성을 보였다. Ciprofloxacin에 낮은 내성률을 보였지만 비임상 검체에서 분리된 NTS 2균주에서 qnrS1형 유전자를 검출하였다. 결론: 국내 NTS의 ampicillin 내성률은 임상 균주와 비임상 균주 모두 높았으나 trimethoprim-sulfamethoxazole 내성률은 분리된 검체에 따라서 다양하였다. Extended-spectrum cephalosporin 내성률은 낮았으나, CTX-M-15형 ESBL 생성 균주와 CMY-2형 PABL 생성 균주가 검출되었다. blaCMY-2형 유전자 양성인 S. Typhimurium 4균주는 인수공통 감염의 가능성을 시사하였다. NTS에서 내성 유전자들이 전파하는 것을 막기 위한 지속적인 노력이 필요할 것으로 판단하였다.
Abstract
Background: The emergence of non-typhoidal Salmonella (NTS) with decreased susceptibilities to fluoroquinolone, ampicillin, or ceftriaxone has been reported worldwide. However, current surveillance studies of resistance among NTS in Korea are limited. Thus, the antimicrobial susceptibilities; resistance mechanisms such as extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC β-lactamase (PABL), and plasmid-mediated quinolone resistance (PMQR); and molecular epidemiologic characteristics were investigated in the present study. Methods: National Institute of Health and National Veterinary Research and Quarantine Service collected NTS strains from 219 clinical and 293 non-clinical specimens from 2006 to 2008. The antimicrobial susceptibilities were determined using the Clinical and Laboratory Standards Institute disk diffusion test. ESBL, PABL, and qnr genotyping were performed using PCR and nucleotide sequencing. Pulsed-field gelelectrophoresis was used for the molecular epidemiologic study. Results: The resistance to ampicillin in clinical and non-clinical NTS was 49% and 18 to 47%, respectively. The resistance rates to trimethoprim-sulfamethoxazole in clinical and non-clinical NTS were 8% and 0 to 41%, respectively. The rates to extended- spectrum cephalosporin were 0 to 1%. One CTX-M- 15-producing isolate and four CMY-2-producing isolates were detected. Notably, PFGE analysis showed four isolates carrying blaCMY-2, including one non-clinical strain had high clonality. Although the rate of ciprofloxacin resistance was very low, two qnrS1-carrying NTS strains were detected in non-clinical specimens. Conclusion: The resistance rates to ampicillin in both clinical and non-clinical NTS were high, while those to trimethoprim-sulfamethoxazole varied depending on the specimen. NTS strains harboring CTX-M-15-type ESBL or CMY-2-type PABL were detected even though the resistance rates to cephalosporins were very low. Four NTS strains carrying the blaCMY-2-gene implied zoonotic infection. Continuous effort to minimize transfer of resistance genes in NTS is necessary.
참고문헌 (24)
- Lee HJ, "Salmonellosis", Korean J Clin Microbiol, 4, pp.5~10 (2001)
- Parry CM, "Antimicrobial resistance in typhoidal and nontyphoidal salmonellae", Curr Opin Infect Dis, 21, pp.531~538 (2008)
- Lee K, "Diversity of TEM-52 extended-spectrum beta-lactamase-producing non-typhoidal Salmonella isolates in Korea", J Antimicrob Chemother, 52, pp.493~496 (2003)
- Arlet G, "Salmonella resistant to extended-spectrum cephalosporins: prevalence and epidemiology", Microbes Infect, 8, pp.1945~1954 (2006)
- Miriagou V, "Expandedspectrum cephalosporin resistance in non-typhoid Salmonella", Int J Antimicrob Agents, 23, pp.547~555 (2004)
- Centers for Disease Control and Prevention (CDC), "Outbreak of multidrug-resistant Salmonella Newport--United States, January- April 2002", MMWR Morb Mortal Wkly Rep, 51, pp.545~548 (2002)
- Robicsek A, "The worldwide emergence of plasmid-mediated quinolone resistance", Lancet Infect Dis, 6, pp.629~640 (2006)
- Wang M, "Plasmid-mediated quinolone resistance in clinical isolates of Escherichia coli from Shanghai, China", Antimicrob Agents Chemother, 47, pp.2242~2248 (2003)
- 정진용, "Increasing incidence of quinolone resistance in human non-typhoid Salmonella enterica isolates in Korea and mechanisms involved in quinolone resistance", Journal of Antimicrobial Chemotherapy, 56(6), pp.1111~1114, Oxford University Press
- Gay K, "Plasmid-mediated quinolone resistance in non-Typhi serotypes of Salmonella enterica", Clin Infect Dis, 43, pp.297~304 (2006)
- Sjölund-Karlsson M, "Emergence of plasmid-mediated quinolone resistance among non-Typhi Salmonella enterica isolates from humans in the United States", Antimicrob Agents Chemother, 53, pp.2142~2144 (2009)
- Performance standards for antimicrobial susceptibility testing; nineteenth informational supplement, "Clinical and Laboratory Standards Institute", CLSI, ~, pp.Document M100-S19 (2009)
- Drieux L, "Phenotypic detection of extended-spectrum beta-lactamase production in Enterobacteriaceae: review and bench guide", Clin Microbiol Infect, 14(1), pp.90~103 (2008)
- Pérez-Pérez FJ, "Detection of plasmid-mediated AmpC beta-lactamase genes in clinical isolates by using multiplex PCR", J Clin Microbiol, 40, pp.2153~2162 (2002)
- Tenover FC, "Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing", J Clin Microbiol, 33, pp.2233~2239 (1995)
- Ran L, "Laboratory-based surveillance of nontyphoidal Salmonella infections in China", Foodborne Pathog Dis, 8, pp.921~927 (2011)
- Esaki H, "Antimicrobial susceptibility of Salmonella isolated from cattle, swine and poultry (2001-2002): report from the Japanese Veterinary Antimicrobial Resistance Monitoring Program", J Antimicrob Chemother, 53, pp.266~270 (2004)
- Crump JA, "Emerging Infections Program NARMS Working Group. Antimicrobial resistance among invasive nontyphoidal Salmonella enterica isolates in the United States: National Antimicrobial Resistance Monitoring System, 1996 to 2007", Antimicrob Agents Chemother, 55, pp.1148~1154 (2011)
- Al-Mashhadani M, "Foreign travel and decreased ciprofloxacin susceptibility in Salmonella enterica infections", Emerg Infect Dis, 17, pp.123~125 (2011)
- Yong D, "Nosocomial outbreak of pediatric gastroenteritis caused by CTX-M- 14-type extended-spectrum beta-lactamase-producing strains of Salmonella enterica serovar London", J Clin Microbiol, 43, pp.3519~3521 (2005)
- Tamang MD, "Emergence of extended-spectrum beta-lactamase (CTX-M-15 and CTX-M-14)-producing nontyphoid Salmonella with reduced susceptibility to ciprofloxacin among food animals and humans in Korea", J Clin Microbiol, 49, pp.2671~2675 (2011)
- Song W, "Appearance of Salmonella enterica isolates producing plasmid-mediated AmpC beta-lactamase, CMY-2, in South Korea", Diagn Microbiol Infect Dis, 52, pp.281~284 (2005)
- Sjölund-Karlsson M, "Plasmid-mediated quinolone resistance among non- Typhi Salmonella enterica isolates", USA. Emerg Infect Dis, 16, pp.1789~1791 (2010)
- Antunes P, "First description of qnrS1-IncN plasmid in a ST11 Salmonella Enteritidis clinical isolate from Portugal", Diagn Microbiol Infect Dis, 69, pp.463~465 (2011)