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1 Ann Clin Microbiol Vol. 18, No. 4, December, pissn eissn Active Surveillance of Multidrug-Resistant Organisms with Rapid Detection Methods for Infection Control Young Ah Kim 1, Kyungwon Lee 2 1 Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital, Goyang, 2 Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea Antibiotic-resistant bacteria have become an increasingly serious problem in Korea, and multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), and multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii have increased over the recent years. More seriously, the recent emergence of carbapenem resistance among Enterobacteriaceae is thought to be an urgent worldwide threat. Active surveillance have been identified as an important tool as an intensified infection control intervention for the control of MRSA and VRE and may be also an effective strategy for multidrug-resistant Gram-negative bacilli. Rapid detection using molecular methods could aid in the timely detection of MDRO carriers, and adequate application of infection control strategy could reduce the transmission of MDROs within hospital settings. (Ann Clin Microbiol 2015;18: ) Key Words: Surveillance, Infection control, Molecular diagnostic testing, Multidrug-resistance INTRODUCTION 지난 60여년동안여러가지항균제에대하여내성을보이는다제내성세균이증가해왔다. 미국질병관리본부 (Centers for Disease Control and Prevention, CDC) 는이러한다제내성세균에의한감염증은치료가어렵다는위험성을알리고, 전파를막기위한노력을기울이고자, 주요내성세균을그심각성에따라 3군으로나누어보고하였다 [1]. 즉, carbapenem 내성 Enterobacteriaceae (CRE) 가긴급한위협 (urgent threat) 으로, methicillin 내성 Staphylococcus aureus (MRSA), vancomycin 내성 enterococcus (VRE), 다제내성 Pseudomonas aeruginosa (MRPA) 및다제내성 Acinetobacter baumannii (MRAB) 가심각한위협 (serious threat) 으로분류되고있다 [1]. 다제내성세균에의한감염은치료항균제의심각한제약, 병원재원기간의증가, 의료비용과치사율의증가등과연관되어국민건강과보건에커다란위험이되고있다 [2-6]. 이에따라우리나라에서도다제내성세균에대한감염관리를강화하고있는데 2010년부터 감염병의예방및관리에관한법률 에의해주요다제내성세균 6종을표본감시의대상으로지정 하여관리하고있다 [7]. 다제내성세균의병원내확산을막기위해서는근거에의한 (evidence-based) 다방면의감염관리전략이필요하며이에는효과적인감염관리, 신속하고정확한진단, 적절한항균제사용등이포함된다. 내성세균의감시는임상검체의배양에서분리된세균만을대상으로통상적으로시행하는수동적감염감시 (passive surveillance) 뿐아니라, 무증상의다제내성세균보균자를검출하는적극적감염감시 (active surveillance) 도감염관리의중요한요소이다 [8]. 적극적감염감시가효과적으로이루어지려면빠른시간내에결과를얻어보균자의격리등의조치등이지연되지않아야하므로전통적인배양을기반으로한방법으로는한계가있어분자유전학적방법을이용한신속검출법의필요성이점점커지고있다 [9]. 본종설에서는최근소개되고있는주요다제내성세균의신속검출법을소개하고그유용성을검토해보고자한다. Received 16 September, 2015, Revised 30 November, 2015, Accepted 1 December, 2015 Correspondence: Kyungwon Lee, Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. (Tel) , (Fax) , ( ) leekcp@yuhs.ac c The Korean Society of Clinical Microbiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 103

2 104 Ann Clin Microbiol 2015;18(4): CURRENT SITUATION OF MULTIDRUG-RESISTANT ORGANISMS IN KOREA Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) 에서보고한 2011년에분리된다제내성세균의내성률을보면 MRSA 67%, vancomycin 내성 Enterococcus faecium 23%, cefotaxime 내성 Escherichia coli 21%, fluoroquinolone 내성 E. coli 36%, cefotaxime 내성 Klebsiella pneumoniae 29%, imipenem 내성 P. aeruginosa 및 Acinetobacter spp. 가각각 21% 와 63% 에달한다 [10]. 최근 10년간은포도당비발효세균중에서 carbapenem 내성세균이증가한것이특이한데, carbapenem 내성 P. aeruginosa의증가가병원내 carbapenem 사용의증가와연관이있다고한다 [11]. 한국에서 carbapenemase 생성 Enterobacteriaceae (CPE) 는아직드문편이지만, 2010년부터시작된질병관리본부의표본감시에의하면 K. pneumoniae carbapenemase (KPC), New Delhi metallo-βlactamase (NDM), Verona integron-encoded metallo-β-lactamase (VIM), imipenemase (IMP), oxacillinase-48 (OXA-48) 등의 carbapenemase를생성하는장내세균군이검출되어왔고, CPE의분리는점점증가하는추세이다 [12,13]. 국내의내성률자료와미국과유럽의중간내성을포함하는비감수성률자료의직접적인비교는어렵겠지만, 국내와미국과유럽병원의중환자실환자에서분리된그람음성세균을비교해보면, 국내가좀더내성률이높음을알수있었다 (Table 1) [10,14]. 특히 3세대 cephalosporin에대한 E. coli의내성률은국내의경우 38% 에달하는데비해미국과유럽은각각 12% 와 17% 의비감수성률을보였다 [10,14]. K. pneumoniae의 3세대 cephalosporin에대한내성률은국내의경우 45% 에달하는데비해미국의경우 Klebsiella spp. 의비감수성률은 13% 에불과하였다 [10,14]. P. aeruginosa의경우국내의 carbapenem에대한내성률은 32% 로미국의비감수성률은 30%, 유럽의비감수 성률은 31% 로국내의내성률이약간높았다 [10,14]. 국내분리 Acinetobacter spp. 의 carbapenem에대한내성률은 83% 로미국의비감수성률 56%, 유럽의비감수성률 62% 보다현저히높았다 [10,14]. ACTIVE SURVEILLANCE FOR INFECTION CONTROL 병원의미생물검사실과감염관리실은병원내감염관리활동의일환으로통상배양에서분리되는다제내성세균의자료를분석하여항균제감수성양상 (antibiogram), 발생률 (incidence), 감염률 (infection rate) 등을감시하는수동적감염감시를시행하고있다. 통상적인미생물검사결과의수동적감시는광범위한지역의내성세균의역학 (epidemiology) 의변화를파악하는데도유용하게이용될수있다 [15]. 통상적배양법으로다제내성세균의보균자를검출하는것은너무늦기때문에, 적극적감염감시가필요하다 [8]. 배양을이용한적극적감염감시와접촉주의 (contact precaution) 가 MRSA 나 VRE 감염방지를위해중요하다는보고가있다 [16]. 다제내성그람음성균에대해서는그리스의신생아실에서발생한 A. baumannii 집단감염을매주변배양을이용한적극적감염감시등의감염관리지침을적용하여효과적으로관리하였다는보고가있다 [17]. 또한이탈리아의한신생아집중치료실에서는배양을통한적극적감염감시로많은신생아들이 KPC-생성 K. pneumoniae의보균자임을밝히고접촉주의등의감염관리지침으로효과적으로관리하였다고보고하였다 [18]. 전통적인배양법을이용한보균자검출에는 2-3일정도의검사시간이소요된다. 표준화된방법으로는 MRSA 보균자검출을위한비강배양 [19], VRE 보균자검출을위한변또는직장면봉배양등이있다 [20]. 다제내성그람음성막대균의보균자검출을위해서는직장면봉배양을하며필요한경우구강인두, 서혜부, 농검체를추가로배양하도록추천되지만표준화된 Table 1. Antimicrobial susceptibility of clinically important Gram-negative bacteria from intensive care units in Korea, United States and Europe Antimicrobial agents E. coli Klebsiella spp.* P. aeruginosa Acinetobacter spp. Region K U E K U E K U E K U E Susceptibility R% NS% NS% R% NS% NS% R% NS% NS% R% NS% NS% 3 rd Cephalosporin Carbapenem Fluoroquinolone Gentamicin *Klebsiella spp. in Korea was K. pneumoniae. Abbreviations: K, Korea; U, United States; E, Europe (Belgium, France, Germany, Ireland, Italy, Portugal, Spain, Sweden, and United Kingdom); R%, resistance rate; NS%, non-susceptibility rate; Susceptibiity data modified from KONSAR surveillance [10] and from SENTRY surveillance [14]; -, no reported data.

3 Young Ah Kim and Kyungwon Lee : Active Surveillance with Rapid Detection Methods 105 배지가없어어려움이있다. 발색배지 (chromogenic agar) 는세균집락이자라면추가동정없이보고할수있으므로통상적인배양보다빠른시간내에결과보고도가능하다. 다제내성세균의신속한검출을위하여배양된집락에서항균제내성유전자를분자유전학적방법으로검출하는것도중요한기법이며, 다양한상품화된제품들이이미개발되어있다. 이방법들은전통적인배양법보다는빠른결과를얻을수있는장점이있으나, 여전히순수배양집락을얻는과정은필요하다. 따라서더욱신속한결과를얻기위하여검체에서직접다제내성세균을검출하는방법이개발되어왔다. 적극적감염감시를적용할때는비용, 인력등의자원문제, 보균자고위험군의선정, 적절한시간내보고및적합한간격으로시행, 검사법의선정등이고려되어야한다. 감염관리활동이지연되지않으려면신속히적극적감염감시의결과를얻는것이중요하며이상적으로는 2시간이내결과를보고하는것이필요하다 [9]. RAPID DETECTION METHODS FOR MULTIDRUG-RESISTANT GRAM-POSITIVE COCCI: MRSA AND VRE MRSA 분리를위해발색배지로 ChromID MRSA (biomérieux, Marcy l'etoile, France), BBL CHROMagar MRSA (BD Diagnostics, Sparks, MD, USA), MRSASelect (Bio-Rad Laboratories, Redmond, WA, USA), 및 Spectra MRSA (Remel, Lenexa, KS, USA) 가 FDA의승인을받았으며 [21], 각각의발색배지의성능은 Table 2에정리하였다 [22-25]. VRE를검출하기위한발색배지로는 ChromID VRE (biomérieux), VRESelect (Bio-Rad Laboratories), Spectra VRE (Remel) 등이 FDA의승인을받았으며 [26], 각각의발색배지의성능은 Table 2에정리하였다 [26-29]. 분자유전학적방법으로검체에서직접 MRSA를검출하는방법들이개발되어왔는데, 비강검체에는 BD GeneOhm MRSA ACP (BD Diagnostics, San Diego, CA, USA), Xpert Table 2. Performance of chromogenic media for detection of methicillin-resistant S. aureus and vancomycin-resistant enterococcus Media % Sensitivity % Specificity % PPV % NPV Reference ChromID MRSA (biomérieux) CHROMagar MRSA II (BD Diagnostics) MRSASelect (Bio-Rad Laboratories) Spectra MRSA (Remel) ChromID VRE (biomérieux) VRESelect (Bio-Rad Laboratories) Spectra VRE (Remel) 95.6 (24 hr) 58 (18 hr) 88 (24 hr) 96 (48 hr) 80.8 (18 hr) 90.9 (24 hr) 99 (48 hr) (18 hr) 91.9 (24 hr) 99 (48 hr) (18 hr) 96 (24 hr) 96 (48 hr) 87.9 (18 hr) 94.9 (24 hr) (18 hr) 96 (24 hr) (24 hr) 88.2 (48 hr) (24 hr) 95.8 (24 hr) 92.5 (48 hr) 99.7 (24 hr) 98.7 (48 hr) 98.7 (18 hr) 98.1 (24 hr) 97.9 (48 hr) (18 hr) 99.5 (24 hr) 99 (48 hr) (24 hr) 82.5 (48 hr) 99 (18 hr) 98.5 (24 hr) 97.7 (48 hr) (24 hr) 80.3 (48 hr) (24 hr) 98.6 (48 hr) (24 hr) 95.2 (48 hr) 82.3 (24 hr) 73.1 (48 hr) 97.8 (24 hr) 92.3 (48 hr) 93 (18 hr) 90.9 (24 hr) 90.7 (48 hr) (18 hr) 97.9 (24 hr) 95.2 (48 hr) (24 hr) 46.6 (48 hr) 94.6 (18 hr) 93.1 (24 hr) 90 (48 hr) (24 hr) 44.6 (48 hr) (24 hr) 97.8 (48 hr) (24 hr) 93.5 (48 hr) 99.1 (24 hr) 93.7 (18 hr) 98.1 (24 hr) 99.4 (48 hr) 96.1 (18 hr) 98.1 (24 hr) 99.8 (48 hr) (18 hr) 98.4 (24 hr) 99.8 (48 hr) (18 hr) 99.4 (24 hr) 99.2 (48 hr) 97.5 (18 hr) 99 (24 hr) (18 hr) 99.4 (24 hr) (24 hr) 90.7 (48 hr) (24 hr) Abbreviations: PPV, positive predictive value; NPV, negative predictive value.

4 106 Ann Clin Microbiol 2015;18(4): MRSA (Cepheid, Sunnyvale, CA, USA), Xpert SA Nasal Complete (Cepheid) 및 LightCycler MRSA advance test (Roche Diagnostics, Basel, Switzland) 가 FDA의승인을받은방법이다 [21]. 국내의제품으로는 multiplex PCR법인 Seeplex MRSA ACE Detection (Seegene Inc., Seoul, Korea) 가상품화되어있다 [30]. 각각의분자검사법의성능은 Table 3에정리하였다 [22,31-36]. 분자유전학적방법으로 MRSA를검출하는방법은주로 meca 유전자를표적으로하고있다 [37]. 하지만 meca 유전자를표적으로하는검사는 coagulase 음성 staphylococcus나 methicillin 감수성 S. aureus가 meca와상동성이높은유전자를가지고있어위양성을보일수있다 [9]. 이러한위양성을극복하기위해서 SCCmec-orfX junction을표적으로하는검사가개발되었다 [38]. 중합효소연쇄반응법을이용하여 MRSA에대해적극적감시를시행할경우는발색배지를이용할때보다좀더신속하게보고할수있다 [39]. 입원 24시간이내에 MRSA 보균자여부를 XpertMRSA assay (Cepheid) 로검출한결과, 배양에의한적극적감염감시에비해보고시간의단축으로격리를적용하는시간은짧아졌지만, 병원내 MRSA의감염을감소시키지는못했다고하였다 [40]. 분자유전학적방법으로검체에서직접 VRE를검출할수있 는방법으로대변혹은직장면봉검체를이용하는 BD Gene- Ohm VanR assay (BD Diagnostics), LightCycler vana/vanb detection assay (Roche Diagnostics) 및 Xpert vana/vanb assay (Cepheid) 가있다 [41]. 국내의제품으로는 multiplex PCR법인 Seeplex VRE ACE detection (Seegene Inc.) 가상품화되어있다 [42,43]. 각각의분자검사법의성능은 Table 3에정리하였다 [44-48]. 분자유전학적방법으로 VRE를검출하는방법에도제한점이있는데대부분의방법이배양보다민감하게 VRE을검출하고있으나 MRSA와는달리집락을제거하는효과적인약제가개발되어있지않기때문에선별검사의유용성이떨어지며, vanb 를가지고있는혐기성세균에의해위양성을보일수있음을주의해야한다고하였다 [9]. RAPID DETECTION METHODS FOR MULTIDRUG-RESISTANT GRAM- NEGATIVE BACILLI: CPE CPE의검출을위하여질병관리본부에서는의심되는균주에대하여 modified Hodge test와 carbapenemase inhibition test를사용하는지침을권장하고있다 [49]. 그러나이방법은통상적인배양에서분리되는 CPE 감시를위해사용할수있으나적 Table 3. Performance of molecular methods for detection of methicillin-resistant S. aureus and vancomycin-resistant enterococcus Diagnostics Comparators % Sensitivity % Specificity % PPV % NPV Reference GeneOhm MRSA ACP Culture (BD Diagnostics) Culture Xpert MRSA Culture (Cepheid) Culture Culture Culture Xpert SA Nasal Culture Complete (Cepheid) LightCycler MRSA Culture (Roche Diagnostics) Culture GeneOhm VanR Culture (BD Diagnostics) Culture VRE culture isolates 40 (vana) 93.3 (vana) 80 (vana) 70 (vana) 46 (van +) 100 (vanb) 14.9 (vanb) 7 (vanb) 100 (vanb) Direct van PCR 43.5 (vana) 100 (vana) 100 (vana) 67.5 (vana) 46 in stool 100 (vanb) 20.6 (vanb) 37.2 (vanb) 100 (vanb) LightCycler vana/vanb Culture (V-MIC 6) (Roche Diagnostics) Culture (V-MIC 8) Xpert vana/vanb assay Culture (Cepheid) VRE culture isolates 70 (vana) 83.3 (vana) 73.7 (vana) 80.6 (vana) 46 (van +) 66.7 (vanb) 12.8 (vanb) 4.7 (vanb) 85.7 (vanb) Direct van PCR 73.9 (vana) 92.6 (vana) 89.5 (vana) 80.6 (vana) 46 in stool 87.5 (vanb) 14.7 (vanb) 32.6 (vanb) 71.4 (vanb) Abbreviations: PPV, positive-predictive value; NPV, negative-predictive value; V-MIC, vancomycin minimal inhibitory concentration (μg/ml).

5 Young Ah Kim and Kyungwon Lee : Active Surveillance with Rapid Detection Methods 107 극적감시배양을위해서사용하기에는번거롭고검사시간이너무긴단점이있다. 좀더신속하고간편하게 CPE (Oxoid) 를검출할수있는발색배지로는 Brilliance CRE (Oxoid) 와 ChromID Carba (biomérieux) 등이있으며, Brilliance CRE는 10 5 CFU 이상의접종에서민감도 82% 와특이도 60% 를보였고, ChromID Carba (biomérieux) 는민감도는 96% 와특이도 76% 를보였다 [50]. 발색배지외에도 CPE를신속하게동정하기위해 Carba NP Test (biomérieux) 를사용할수있는데, 원리는 carbapenemase 를생성하는순수배양된집락인경우시약에포함된 carbapenem을분해하여색변화를일으키는것을검출하는것으로 Enterobacteriaceae뿐아니라 P. aeruginosa나 A. baumannii에도적용할수있다 [51,52]. 분자유전학적방법으로 CPE를검출하는것은내성유전자가명확하고단순한 MRSA (meca) 나 VRE (vana) 에비해어려움이있는데, CPE의 carbapenemase 생성에는다양한내성유전자가관여하고있기때문이다 [53]. 더욱이 carbapenemase를생성하지않더라도유출펌프나외막단백에변화가있는균주의경우 ESBL이나 AmpC-β-lactamase 생성만으로도 carbapenem에내성을보일수있다 [54-56]. Check-MDR (Check-Points, Wageningen, Netherlands) 은장내세균이나포도당비발효세균의 carbapenemase, ESBL, AmpCβ-lactamase 등의다제내성유전자를한번에검출하는 microarray법이며, 고가이지만높은민감도와특이도를보인다 [57]. Check-Direct CPE (Check-Points) 는 multiplex real-time PCR법을이용한방법으로순배양된집락뿐아니라직장면봉에서도직접검사가가능하며주요 carbapenemase인 KPC, OXA-48, OXA-181, VIM과 NDM의유전자를 3시간이내에검출할수있으며민감도와특이도가우수하였다 [58]. 최근에개발된 Xpert MDRO (Cephid) 는변검체로직접검사가가능하며 KPC, NDM, VIM carbapenemase 유전자를검출하는자동화된방법이며 VIM과 KPC에대해각각민감도 100% 와특이도 99.4%/ 99%, 양성예측도 81.8%/93% 및음성예측도 100% 였다 [59]. CONCLUSIONS 다제내성세균의신속한검출은무증상의보균자를파악하여신속한감염관리전략을적용할수있어서다제내성세균의감염의전파를줄이는효과가있을것으로생각된다. 하지만미생물검사실에서이를통상적으로사용하려면고비용의분자유전학적방법을이용한신속한다제내성균의검출이전통적인배양법에비해임상적으로좀더유용함을확인할필요가있겠고, 특히다제내성그람음성막대균에대한많은연구가필요하리라생각된다. 효과적인감염관리를위해서는빠른시간내에결과를얻는 것이중요하므로순수배양을하지않고도검체에서직접내성유전자를검출하는방법이지속적으로개발되어야하겠고, 특히비강뿐만아니라혈액, 소변, 변등여러검체에적용이가능한것이실제적으로검사실에도움이되겠다. 또한그람음성막대균에서는다양한내성유전자가복합적으로작용하는경우가많으므로다양한내성기전을검출할수있는검사법의개발이필요하다. 마지막으로신속하게다제내성세균의집락을확인후적절한감염관리가이루어질수있도록효과적인감염관리전략의개발및유용성에대한연구도필요하다고하겠다. REFERENCES 1. CDC. CDC web sites on Antibiotic Resistance Threats in the United States, / [Online] (last visited on 16 September 2015). 2. Martín-Loeches I, Diaz E, Vallés J. Risks for multidrug-resistant pathogens in the ICU. Curr Opin Crit Care 2014;20: DeLeo FR and Chambers HF. Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. J Clin Invest 2009; 119: DiazGranados CA and Jernigan JA. Impact of vancomycin resistance on mortality among patients with neutropenia and enterococcal bloodstream infection. J Infect Dis 2005;191: Esterly JS, Griffith M, Qi C, Malczynski M, Postelnick MJ, Scheetz MH. Impact of carbapenem resistance and receipt of active antimicrobial therapy on clinical outcomes of Acinetobacter baumannii bloodstream infections. Antimicrob Agents Chemother 2011;55: Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008;29: Korea Centers for Disease Control and Prevention. Infection Control Guidelines for Multidrug Resistant Microorganisms in Healthcare Facilities. Together0302.jsp?menuIds=HOME001-MNU1154-MNU0004-MN U0088&fid=51&q_type=title&q_value=%EB%8B%A4%EC%A0% 9C%EB%82%B4%EC%84%B1%EA%B7%A0&cid=18712&page Num=/ [Online] (last visited on 16 September 2015). 8. Backman C, Taylor G, Sales A, Marck PB. An integrative review of infection prevention and control programs for multidrugresistant organisms in acute care hospitals: a socio-ecological perspective. Am J Infect Control 2011;39: Diekema DJ and Pfaller MA. Rapid detection of antibiotic-resistant organism carriage for infection prevention. Clin Infect Dis 2013;56: Lee Y, Kim YA, Song W, Lee H, Lee HS, Jang SJ, et al. Recent trends in antimicrobial resistance in intensive care units in Korea. Korean J Nosocomial Infect Control 2014;19: Xu J, Duan X, Wu H, Zhou Q. Surveillance and correlation of antimicrobial usage and resistance of Pseudomonas aeruginosa: a hospital population-based study. PLoS One 2013;8:e Korea Centers for Disease Control and Prevention. Emergence and characteristics of carbapenemase-producing Enterobacteriaceae (CPE) in Korea,

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7 Young Ah Kim and Kyungwon Lee : Active Surveillance with Rapid Detection Methods 109 and glycopeptide-resistant Enterococcus species. J Clin Microbiol 2008;46: Lee SY, Park KG, Lee GD, Park JJ, Park YJ. Comparison of Seeplex VRE detection kit with ChromID VRE agar for detection of vancomycin-resistant enterococci in rectal swab specimens. Ann Clin Lab Sci 2010;40: Kim DH, Lee JH, Ha JS, Ryoo NH, Jeon DS, Kim JR. Evaluation of the usefulness of selective chromogenic agar medium (chromid VRE) and multiplex PCR method for the detection of vancomycinresistant enterococci. Korean J Lab Med 2010;30: Werner G, Serr A, Schütt S, Schneider C, Klare I, Witte W, et al. Comparison of direct cultivation on a selective solid medium, polymerase chain reaction from an enrichment broth, and the BD GeneOhm TM VanR Assay for identification of vancomycin-resistant enterococci in screening specimens. Diagn Microbiol Infect Dis 2011;70: Usacheva EA, Ginocchio CC, Morgan M, Maglanoc G, Mehta MS, Tremblay S, et al. Prospective, multicenter evaluation of the BD GeneOhm VanR assay for direct, rapid detection of vancomycin-resistant Enterococcus species in perianal and rectal specimens. Am J Clin Pathol 2010;134: Gazin M, Lammens C, Goossens H, Malhotra-Kumar S; MOSAR WP2 Study Team. Evaluation of GeneOhm VanR and Xpert vana/vanb molecular assays for the rapid detection of vancomycin-resistant enterococci. Eur J Clin Microbiol Infect Dis 2012; 31: Sloan LM, Uhl JR, Vetter EA, Schleck CD, Harmsen WS, Manahan J, et al. Comparison of the Roche LightCycler vana/ vanb detection assay and culture for detection of vancomycinresistant enterococci from perianal swabs. J Clin Microbiol 2004; 42: Bourdon N, Bérenger R, Lepoultier R, Mouet A, Lesteven C, Borgey F, et al. Rapid detection of vancomycin-resistant enterococci from rectal swabs by the Cepheid Xpert vana/vanb assay. Diagn Microbiol Infect Dis 2010;67: The Korean Society of Clinical Microbiology. Guideline of diagnostic method of CPE. [Online] (last visited on 16 September 2015). 50. Wilkinson KM, Winstanley TG, Lanyon C, Cummings SP, Raza MW, Perry JD. Comparison of four chromogenic culture media for carbapenemase-producing Enterobacteriaceae. J Clin Microbiol 2012;50: Dortet L, Poirel L, Nordmann P. Rapid identification of carbapenemase types in Enterobacteriaceae and Pseudomonas spp. by using a biochemical test. Antimicrob Agents Chemother 2012;56: Dortet L, Poirel L, Errera C, Nordmann P. CarbAcineto NP test for rapid detection of carbapenemase-producing Acinetobacter spp. J Clin Microbiol 2014;52: Bush K. Alarming β-lactamase-mediated resistance in multidrugresistant Enterobacteriaceae. Curr Opin Microbiol 2010;13: Szabó D, Silveira F, Hujer AM, Bonomo RA, Hujer KM, Marsh JW, et al. Outer membrane protein changes and efflux pump expression together may confer resistance to ertapenem in Enterobacter cloacae. Antimicrob Agents Chemother 2006;50: Yang FC, Yan JJ, Hung KH, Wu JJ. Characterization of ertapenem-resistant Enterobacter cloacae in a Taiwanese university hospital. J Clin Microbiol 2012;50: Lee Y, Choi H, Yum JH, Kang G, Bae IK, Jeong SH, et al. Molecular mechanisms of carbapenem resistance in Enterobacter cloacae clinical isolates from Korea and clinical outcome. Ann Clin Lab Sci 2012;42: Naas T, Cuzon G, Bogaerts P, Glupczynski Y, Nordmann P. Evaluation of a DNA microarray (Check-MDR CT102) for rapid detection of TEM, SHV, and CTX-M extended-spectrum β- lactamases and of KPC, OXA-48, VIM, IMP, and NDM-1 carbapenemases. J Clin Microbiol 2011;49: Nijhuis R, Samuelsen O, Savelkoul P, van Zwet A. Evaluation of a new real-time PCR assay (Check-Direct CPE) for rapid detection of KPC, OXA-48, VIM, and NDM carbapenemases using spiked rectal swabs. Diagn Microbiol Infect Dis 2013;77: Tenover FC, Canton R, Kop J, Chan R, Ryan J, Weir F, et al. Detection of colonization by carbapenemase-producing Gramnegative bacilli in patients by use of the Xpert MDRO assay. J Clin Microbiol 2013;51:

8 110 Ann Clin Microbiol 2015;18(4): = 국문초록 = 감염관리를위한신속검출법을이용한다제내성세균의적극적감염감시 1 국민건강보험공단일산병원진단검사의학과, 2 연세대학교의과대학진단검사의학교실, 세균내성연구소김영아 1, 이경원 2 여러항균제에대해내성을보이는다제내성세균은한국에서점점심각한문제가되고있고, 메티실린내성황색포도알균 (MRSA), 반코마이신내성장알균 (VRE), 다제내성녹농균및다제내성 Acinetobacter baumannii 등이점점증가하고있다. 더욱이최근에는카바페넴약제도내성을보이는장세균군이출현하여전세계적으로퍼지고있어보건에긴급한위협이되고있다. 무증상의보균자에게서다제내성세균을검출하는적극적감염감시 (active surveillance) 는 MRSA와 VRE의감염관리의중요한방법으로사용되고있으며, 다제내성그람음성막대균에대해서도효과적인전략이될수있다. 분자유적학적방법등을이용한신속한다제내성세균의보균자검출과이를통한적절한병원감염정책은의료관련감염의전파를막을수있는핵심요소이다. [Ann Clin Microbiol 2015;18: ] 교신저자 : 이경원, 03722, 서울시서대문구연세로 50 연세대학교의과대학진단검사의학교실, 세균내성연구소 Tel: , Fax: leekcp@yuhs.ac

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