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Carbapenemase-Producing Enterobacterales: Epidemiology, Detection, and Treatment
Biomed Sci Letters 2023;29:109-120
Published online September 30, 2023;  https://doi.org/10.15616/BSL.2023.29.3.109
© 2023 The Korean Society For Biomedical Laboratory Sciences.

Yun Hee Baek1,* and Kyeong Seob Shin2,†,*

1Department of Microbiology, Chungbuk National University College of Medicine, Cheongju 28644, Korea
2Department of Laboratory Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Korea
Correspondence to: Kyeong Seob Shin. Department of Laboratory Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Tel: +82-43-269-6240, Fax: +82-43-271-5243, e-mail: ksshin@chungbuk.ac.kr
*Professor.
Received September 11, 2023; Revised September 21, 2023; Accepted September 21, 2023.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Recently, the explosive increase of carbapenemase-producing Enterobacterales (CPE) in the worldwide poses a serious threat. The purpose of this study is to investigate epidemiology, detection, and treatment of CPE. Three main carbapenemase are reported worldwide, which were KPC, NDM, and OXA-48-like. KPC type are mostly found in USA, China, Europe, and Latin America. NDM type are mostly found in South Asia. OXA-48-like are often seen in the Mediterranean and Northern Africa. In Korea, CPE have increased explosively since 2015. In 2021, 18,099 CPE were isolated, which were Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae in order. The CPE genotype was distributed with KPC, NDM, OXA type in order. Phenotypic detection methods include carbapenemase production tests (CPT) and differential tests of CPE. CPTs include modified Hodge test, modified carbapenem inactivation method (mCIM), Carba NP test, among which mCIM is the most widely used due to easy accessibility and accuracy. A lot of genotypic methods are being done for quick results, and commercialized kits using multiplex real-time PCR and microarray are widely used. Colistin and tigecycline are used as the first line of CPE treatment and are used in combination with second line drugs such as meropenem and fosfomycin.
Keywords : Carbapenemase producing Enterobacterales, Epidemiology, Detection, Treatment
꽌 濡

Carbapenem extended-spectrum 棺-lactamase (ESBL)쓣 룷븿븯뿬 떎뼇븳 棺-lactamase뿉 빐 븞젙븯誘濡 洹몃엺 쓬꽦 媛꾧퇏뿉꽌 理쒗썑源뚯 궗슜븷 닔 엳뒗 빆깮젣씠떎(Jacoby and Munoz-Price, 2005). 理쒓렐뿉 carbapenem쓣 媛닔遺꾪빐븯뒗 棺-lactamase (carbapenemase)쓽 異쒗쁽 洹몃엺 쓬꽦 媛꾧퇏쓽 移섎즺뿉 留ㅼ슦 겙 쐞삊쓣 二쇨퀬 엳떎(Paterson and Doi, 2007; Queenan and Bush, 2007). Carbapenem뿉 븳 궡꽦 1) carbapenemase쓽 깮꽦, 2) ESBL 삉뒗 AmpC 棺-lactamase 깮꽦怨 룎뿰蹂씠뿉 쓽븳 porin쓽 긽떎濡 씤븳 遺덊닾怨쇱꽦(impermeability)씠 룞떆뿉 議댁옱븷 寃쎌슦뿉 굹궇 닔 엳떎. 씠 以묒뿉꽌 carbapenemase쓽 깮꽦씠 媛옣 二쇱슂븳 궡꽦 湲곗쟾씠硫 Ambler쓽 븘誘몃끂궛 쑀궗룄뿉 湲곗큹븳 遺꾨쪟 諛⑸쾿뿉 쓽빐 class A, B, D carbapenemase媛 엫긽쟻쑝濡 以묒슂븯떎(Nordmann and Poirel, 2002) (Table 1).

The classification of carbapenemase and microorganism from which the enzyme was isolated

Ambler classification Enzyme type Microorganisms
Class A KPC, GES, SMEa, NMCa, IMIa Enterobacteriaceae
P. aeruginosa
Class B NDM, IMP, VIM, SIM Enterobacteriaceae
P. aeruginosa
Acinetobacter spp.
Class D OXA Enterobacteriaceae (OXA-48)
Acinetobacter spp. (OXA-23)

Abbreviations: KPC, Klebsiella pneumoniae carbapenemase; GES, Guiana extended spectrum 棺-lactamase; SME, Serratia marcescens enzyme; NMC, non-mtalloenzyme carbapenemase; IMI, imipenemase; NDM, New Delhi metallo-棺-lactamase; IMP, imipenemase; VIM, Verona integron-encoded metallo-棺-lactamase; SIM, Seoul imipenemase; OXA, oxacillinase

aThe genes are presumed to be chromosome and non-mobile



Class A carbapenemase뒗 뿼깋泥 諛 뵆씪뒪誘몃뱶뿉 議댁옱븯뒗뜲, SME (Serratia marcescens enzyme), NMC (non-metalloenzyme carbapenemase) 諛 IMI (imipenemase)뒗 뿼깋泥댁뿉 議댁옱븯怨, KPC (Klebsiella pneumoniae carbapenemase) 諛 GES (Guiana extended spectrum)뒗 뵆씪뒪誘몃뱶뿉 議댁옱븳떎(Walther-Rasmussen and H첩iby, 2007). KPC GES뒗 뵆씪뒪誘몃뱶瑜 넻빐 궡꽦쑀쟾옄瑜 돺寃 쟾떖븯誘濡 엫긽쟻쑝濡 留ㅼ슦 以묒슂븯硫, KPC삎씠 援궡瑜 룷븿븯뿬 쟾꽭怨꾩뿉 媛옣 꼸由 띁졇 엳떎. 븳렪 KPC뒗 遺遺꾩쓽 棺-lactam 젣뿉 궡꽦씠硫 棺-lactamase 뼲젣젣(inhibitor)뿉 뼲젣릺뒗 듅吏뺤쓣 媛뽮퀬 엳떎(Yigit et al., 2001).

Class B carbapenemase뒗 棺-lactam 빆깮젣瑜 媛닔遺꾪빐븯湲 쐞빐 븘뿰씠삩(Zn2+)씠 븘슂븯誘濡 metallo-棺-lactamase (MBL)濡 븣젮졇 엳떎. 뵲씪꽌 EDTA dipicolinic acid 媛숈 2媛 씠삩쓽 chelator뿉 쓽빐 뼲젣릺硫 棺-lactamase 뼲젣젣뿉뒗 뼲젣릺吏 븡뒗떎(Lee et al., 2003; Kimura et al., 2005). 쁽옱源뚯 떎뼇븳 쉷뱷꽦 MBL씠 遺꾨━릺뿀뒗뜲, IMP, VIM, GIM, SPM, SIM, AIM, NDM 벑씠 룷븿맂떎. MBL 쑀쟾옄뒗 Pseudomonas aeruginosa, Acinetobacter, Serratia, Klebsiella pneumoniae, Escherichia coli, Enterobacter, Citrobacter 벑 떎뼇븳 洹몃엺 쓬꽦 媛꾧퇏뿉 띁졇 엳떎(Maltezou, 2009). 옄뿰쟻쑝濡 諛쒖깮븯뒗 紐뉖챺 MBL 뿼깋泥댁뿉 議댁옱븯굹 씤뀒洹몃줎(integron)쓽 援ъ꽦꽦遺꾩쑝濡 議댁옱븯뒗 쉷뱷꽦 MBL 쑀쟾옄뒗 뵆씪뒪誘몃뱶뿉 議댁옱븳떎. MBL 깮꽦 옣궡꽭洹좎뿉꽌 媛옣 쓷븳 쑀쟾삎씤 NDM (New Delhi MBL) 2009뀈 씤룄쓽 蹂묒썝뿉 엯썝븳 뒪썾뜶씤뿉꽌 遺꾨━맂 K. pneumoniae뿉꽌 泥섏쓬 蹂닿퀬릺뿀怨(Yong et al., 2009) 씠썑 湲됯꺽븯寃 利앷븯뿬 쁽옱뒗 媛옣 쓷븳 Class B carbapenemase媛 릺뿀떎. NDM 쑀쟾옄뒗 KPC蹂대떎 蹂듭옟븳 삎깭쓽 씠룞꽦 쑀쟾슂냼(mobile genetic element)濡 議댁옱븯硫 K. pneumoniae 씠쇅쓽 옣궡꽭洹, Acinetobacter spp. 諛 P. aeruginosa 벑뿉꽌룄 遺꾨━릺뿀떎.

Class D carbapenemase뒗 penicillin蹂대떎 oxacillin쓣 뜑 옒 媛닔遺꾪빐븯뒗 꽦吏 븣臾몄뿉 OXA삎 슚냼濡 븣젮졇 엳쑝硫 A. baumannii 옣궡꽭洹좎뿉꽌 遺꾨━맂떎(Walther-Rasmussen and H첩iby, 2006). OXA-23, 24/40, 48, 58, 143, 51씠 carbapenem쓣 媛닔遺꾪빐븯硫 OXA-51쓣 젣쇅븯怨 뵆씪뒪誘몃뱶뿉 議댁옱븳떎. OXA 23/24/40, 58 A. baumannii뿉꽌 遺꾨━릺吏留 OXA-48 옣궡꽭洹좎뿉꽌 遺꾨━릺硫 옣궡꽭洹좎뿉꽌 媛옣 쓷븳 Class D carbapenemase媛 릺뿀떎(Poirel et al., 2012).

씠 뿰援ъ뿉꽌 carbapenemase瑜 깮꽦븯뒗 옣궡꽭洹(carbapenemase-producing Enterobacterales, CPE)쓽 뿭븰, 寃異 洹몃━怨 移섎즺 媛먯뿼愿由ъ뿉 빐 湲곗닠븯떎.

蹂 濡

1. 뿭븰(Epidemiology)

1) 遺꾪룷(Distribution of CPE around the world)

(1) Klebsiella pneumoniae carbapenemase (KPC, Class A)

誘멸뎅뿉꽌 媛옣 쓷븳 carbapenemase濡 1990뀈 North Carolina뿉꽌 泥섏쓬 遺꾨━릺뿀怨(Yigit et al., 2001) 誘멸뎅 쟾 吏뿭 쇅뿉 쑀읇, 븘떆븘, 삤꽭븘땲븘 諛 궓븘硫붾━移 吏뿭源뚯 遺꾨━릺怨 엳떎(Munoz-Price et al., 2013). 듅엳, 誘멸뎅, 以묎뎅, 씠깭由, 洹몃━뒪, 씠뒪씪뿕, 釉뚮씪吏, 븘瑜댄뿨떚굹, 肄쒕\鍮꾩븘 諛 留뚯뿉꽌뒗 KPC媛 샇諛쒗븯硫(endemic), 援궡뿉꽌룄 湲됯꺽엳 솗궛릺怨 엳떎. KPC뒗 쟾泥 CPE 以 媛옣 꼸由 띁졇 엳쑝硫 떎뼇븳 KPC 蹂醫(variant)씠 議댁옱븯뒗뜲 2021뀈源뚯 82媛吏 蹂醫낆씠 蹂닿퀬릺뿀떎(Lebreton et al., 2021). 씠 以묒뿉꽌 KPC-2삎씠 媛옣 꼸由 띁졇 엳쑝硫, 씠뼱꽌 KPC-3삎씠 留롫떎. 援궡뿉꽌룄 KPC-2삎씠 媛옣 슦꽭븯硫 援궡 CPE 솗궛쓽 二쇱슂 썝씤쑝濡 븣젮졇 엳떎(Yoon et al., 2018).

(2) Metallo-棺-lactamases (MBL, Class B)

IMP삎씠 1991뀈 씪蹂몄뿉꽌 泥섏쓬 遺꾨━맂 씠옒 븘떆븘, 쑀읇, 遺곸븘硫붾━移, 궓븘硫붾━移 諛 샇二 벑뿉꽌 遺꾨━릺怨 엳떎. NDM-1씠 씤룄뿉꽌 2009뀈 泥섏쓬 遺꾨━맂(Yong et al., 2009) 씠썑 씤룄, 뙆궎뒪깂, 븘떆븘, 쑀읇, 遺곸븘硫붾━移, 샇二 벑뿉꽌 뿰냽쟻쑝濡 遺꾨━릺뿀怨 P. aeruginosa뿉꽌뒗 KPC NDM씠 룞떆뿉 遺꾨━릺湲곕룄 븯떎. 쁽옱 NDM삎쓽 샇諛 吏뿭 씤룄, 뙆궎뒪깂, 諛⑷씪뜲떆씠硫(Nordmann and Poirel, 2014), 洹 쇅 遺곷, 븘떆븘(以묎뎅, 븳援, 씪蹂, 留), 샇二, 쑀읇 벑뿉꽌룄 蹂닿퀬媛 利앷븯怨 엳떎(Kim et al., 2012). MBL 以 NDM삎씠 媛옣 留롮씠 遺꾨━릺硫 씠 以 NDM-1씠 援궡瑜 룷븿븯뿬 꽭怨꾩뿉꽌 媛옣 쓷븯떎. K. pneumoniae뿉꽌 媛옣 쓷엳 遺꾨━릺吏留(Nordmann and Poirel, 2014) 以묎뎅뿉꽌뒗 Acinetobacter 洹좎쥌뿉꽌 뜑 옄二 遺꾨━맂떎. 씠뒗 NDM-1씠 Acinetobacter 洹좎쥌뿉꽌 옣궡꽭洹좎쑝濡 쟾떖릺뿀쓣 媛뒫꽦쓣 떆궗븳떎(Qin et al., 2014). NDM삎蹂대떎뒗 留ㅼ슦 뱶臾쇱留 IMP삎怨 VIM삎룄 쟾꽭怨꾩뿉꽌 遺꾨━릺怨 엳떎.

(3) Class D carbapenemase (OXA-48 like)

12媛쒖쓽 븘삎쑝濡 遺꾨쪟븯硫, 씠 以 OXA-23, 24/40, 58瑜 媛吏怨 엳뒗 A. baumannii뒗 쑀읇뿉꽌 듅엳 臾몄젣媛 릺怨 엳쑝硫, 븳援쓣 룷븿븳 룞븘떆븘, 以묐룞, 샇二, 궓븘硫붾━移 洹몃━怨 誘멸뎅뿉꽌 遺꾨━릺怨 엳떎. OXA-48삎씠 Turkey뿉꽌 泥섏쓬 遺꾨━맂 씠옒濡 OXA-48삎 옣궡꽭洹좎씠 쟾꽭怨꾨줈 띁議뚯쑝硫, Turkey, 紐⑤줈肄, 由щ퉬븘, 씠吏묓듃, 땲뒪, 씤룄媛 샇諛쒗븯뒗 吏뿭씠떎(Nordmann and Poirel, 2014). 洹 쇅 쑀읇(봽옉뒪, 뒪럹씤, 씠깉由ъ븘), 씪蹂, 궗슦뵒븘씪鍮꾩븘, 븘瑜댄뿨떚굹 벑뿉꽌 遺꾨━릺뿀떎(Lee et al., 2016). OXA-48 븳 媛쒖쓽 븘誘몃끂궛씠 移섑솚맂 OXA-181 씤룄뿉꽌 泥섏쓬 遺꾨━맂 썑 쟾꽭怨꾩뿉꽌 遺꾨━릺怨 엳떎. 洹 쇅 OXA-204 OXA-232룄 OXA-48濡쒕꽣 쑀옒릺뿀떎(Potron et al., 2013).

2) 援궡 遺꾪룷(Distribution of CPE in Korea)

쁽옱 쟾꽭怨꾩뿉꽌 二쇰줈 遺꾨━릺뒗 CPE뒗 KPC, NDM, OXA-48 닚씤뜲, 援궡뿉꽌룄 KPC삎씠 媛옣 留롮쑝硫 씠뼱꽌 NDM, OXA-48 닚쑝濡 遺꾨━릺怨 엳떎. 2010뀈 NDM-1 (Kim et al., 2012)怨 KPC媛 援궡뿉꽌 泥섏쓬 遺꾨━릺뿀怨(Rhee et al., 2010) 2011뀈 K. pneumoniae뿉꽌 KPC-2쓽 泥 踰덉㎏ 吏묐떒諛쒖깮(outbreak) (Hong et al., 2013)씠 깮寃쇰떎. 2013뀈 K. pneumoniae E. coli뿉꽌 OXA-48 蹂씠삎씤 OXA-232씠 吏묐떒쑝濡 諛쒖깮븯쑝硫(Jeong et al., 2015), 씠썑 CPE뒗 吏냽쟻쑝濡 利앷븯뿬 2021뀈뿉 18,099媛쒖쓽 CPE媛 遺꾨━릺뿀떎(KDCPA, 2022). CPE濡 솗씤맂 洹 醫낆 K. pneumoniae (10,463; 57.81%), E. coli, E. cloacae 닚씠뿀쑝硫 쑀쟾삎 KPC (81.77%), NDM (14.67%), OXA (1.94%) 닚쑝濡 遺꾨━릺뿀떎. 듅엳 KPC-2媛 KPC삎쓽 97.95%瑜 李⑥븯怨 NDM -1씠 NDM쓽 79.25% 씠뿀쑝硫 OXA삎 遺遺 OXA-181삎씠뿀떎. 븳렪 OXA-181怨 NDM-5瑜 룞떆뿉 蹂댁쑀븳 61二쇰 룷븿븯뿬 몢 媛吏 씠긽 쑀쟾옄삎쓣 蹂댁쑀븳 洹좎<룄 238二쇰굹 遺꾨━릺뿀떎(KDCPA, 2022) (Fig. 1).

Fig. 1. Distribution of carbapenemase genes isolated from Enterobacterales in Korea. A total of 18,099 CPE isolates were reported in National antimicrobial resistance surveillance 2021 annual report in Korea [KDCPA, 2022].

3) 援궡 遺꾨━二쇱쓽 쑀쟾븰쟻 듅吏(Genetic characteristics in Korea)

KPC瑜 깮꽦븯뒗 CPE媛 쟾꽭怨꾩쟻쑝濡 媛옣 留롮씠 遺꾪룷븯硫 KPC쓽 clone뿉 빐꽌뒗 옒 븣젮졇 엳떎. K. pneumoniae ST258씠 쟾꽭怨꾩쟻쑝濡 媛옣 슦꽭븳 clone씠吏留(Chen et al., 2014), 援궡뿉꽌뒗 K. pneumoniae ST307씠 媛옣 슦꽭븯怨 씠뼱꽌 ST11 닚씠떎(Yoon et al., 2018). 援궡뿉꽌 媛옣 쓷븳 ST307 Italian clone怨 쑀궗븯硫 씠뱾 遺遺 CTX-M 슚냼瑜 룞떆뿉 諛쒗쁽븯뒗 듅吏뺤쓣 媛吏怨 엳떎. ST11뒗 以묎뎅뿉 쑀뻾븯뒗 clone쑝濡 븣젮졇 엳떎. 뵲씪꽌 援궡뿉꽌 ST307 洹좎< ST11 洹좎<쓽 솗궛 援媛 諛 吏뿭媛 援먮쪟쓽 利앷뿉 쓽븳 寃껋엫쓣 떆궗븳떎. KPC-2 KPC-3媛 꽭怨꾩뿉꽌 媛옣 쑀뻾븯뒗 븘삎(subtype)씠吏留(Munoz-Price et al., 2013), 援궡뿉꽌뒗 KPC2, KPC-4, KPC-3 닚쑝濡 遺꾪룷븯怨 엳떎. 븳렪 KPC삎쓽 쟾꽭怨꾩쟻 솗궛 씠룞꽦씠 쎇뼱궃 Tn3 湲곕컲 transposon Tn4401 븣臾몄쑝濡 븣젮졇 엳떎(Naas et al., 2008). Tn4401 transposage 쑀쟾옄, resolvase 쑀쟾옄, blaKPC 쑀쟾옄 洹몃━怨 몢 媛쒖쓽 궫엯꽌뿴(ISKpn6怨 ISKpn7)쓣 媛吏뒗뜲(Lee et al., 2016) (Fig. 2), 닔留롮 뵆씪뒪誘몃뱶 궗씠瑜 嫄대꼫쎇뼱 blaKPC 쑀쟾옄瑜 쟾떖븷 닔 엳뼱 궡꽦쑀쟾옄쓽 솗궛씠 돺떎(Chen et al., 2014). Tn4401 5媛쒖쓽 븘삎씠 엳뒗뜲 ISkpn7怨 blaKPC 궗씠쓽 寃곗넀(deletion)쓽 겕湲곗뿉 뵲씪 굹닃 닔 엳쑝硫, 援궡뿉꽌뒗 Tn4401a媛 媛옣 쓷븯떎. 듅엳 KPC2쓽 Tn4401 떎뼇븯굹, KPC3, 4삎 Tn4401b삎씠 二쇰줈 諛쒓껄릺怨 엳떎(Yoon et al., 2018).

Fig. 2. Structure of genetic elements of blaKPC-2. The blaKPC-2-containing Tn4401 transposon from the plasmid Pnyc is shown in horizontal arrows. Two inverted repeated sequences (IRL and IRR) of Tn4401 are depicted in triangles at either end. Tn4401 has five isoforms which differ by deletion (68~255 bp) just upstream of the blaKPC gene (Lee et al., 2016; Front Microbiol).

2. 寃異 諛⑸쾿(Detection methods)

Carbapenemase 寃異 諛⑸쾿뿉뒗 몴쁽삎쟻 寃궗 쑀쟾삎쟻 寃궗媛 엳쑝硫, 몴쁽삎쟻 寃궗뿉뒗 carbapenemase 寃異쒕쾿(modified Hodge test modified carbapenem inactivation method, Carba NP I test)怨 class A, B, D 媛먮퀎寃궗(EDTA-modified carbapenem inactivation method, double disk synergy test, Carba NP II, MALDI-TOF MS)媛 엳떎.

1) Modified Hodge test (MHT)

2009뀈 CLSI (CLSI, 2009)뿉꽌 carbapenemase쓽 寃異쒖뿉 泥 踰덉㎏濡 沅뚭퀬븯뜕 諛⑸쾿쑝濡 돺怨 媛꾪렪븳 寃궗젅李⑤줈 씤빐 留롮 寃궗떎뿉꽌 씠슜븯怨 엳떎. 씠 諛⑸쾿 CPE濡쒕꽣 carbapenemase媛 諛곗 二쇱쐞濡 솗궛븯뿬 carbapenem뿉 媛먯닔꽦씤 꽭洹좎씠 carbapenem 議댁옱 븯뿉꽌룄 옄엫 닔 엳룄濡 蹂댄샇빐二쇰뒗 썝由щ 씠슜븳 寃궗踰뺤씠떎(Lee et al., 2010). Carbapenem뿉 媛먯닔꽦씤 E. coli瑜 ertapenem 뵒뒪겕 媛숈씠 븳泥쒕같吏뿉 젒醫낇븳 썑 긽洹좎쓣 諛곗뿉 뵒뒪겕 二쇱쐞源뚯 쉷꽑(streak)븳떎. CPE씪 寃쎌슦 諛곗뿉 솗궛릺뼱 엳뒗 ertapenem쓣 媛닔遺꾪빐븯뿬 쉷꽑븳 洹 二쇱쐞뿉 媛먯닔꽦씤 E. coli媛 옄씪寃 맂떎(Fig. 3). MHT쓽 옣젏 돺怨 뿬윭 洹좎<瑜 븳踰덉뿉 떆뿕븷 닔 엳쑝굹, 떒젏 빐꽍씠 二쇨쟻씠怨 carbapenemase쓽 醫낅쪟瑜 媛먮퀎븷 닔 뾾쑝硫, AmpC굹 ESBL怨 媛숈 non-carbapenemase뿉 쓽빐 쐞뼇꽦쓣 蹂댁씪 닔 엳떎. 삉븳 Class A (KPC), Class D (OXA-48), some MBL (IMP, VIM)뿉뒗 슦닔븳 꽦쟻쑝濡 蹂댁씠굹 NDM 벑뿉꽌뒗 꽦쟻씠 醫뗭 븡떎怨 븣젮졇 엳떎(Girlich et al., 2012). 뵲씪꽌 誘멸뎅怨 媛숈씠 KPC삎씠 遺遺꾩씤 굹씪뿉꽌 二쇰줈 궗슜릺怨 엳떎.

Fig. 3. Modified Hodge test using a 10 關g ertapenem disc. Isolates 1, 2 are carbapenemase-producing Enterobacterales (CPE) but isolate 3 is non-CPE. ETP, ertapenem disk.

2) Modified carbapenem inactivation method (mCIM)

寃궗 洹좎< meropenem 뵒뒪겕瑜 븸泥대같吏뿉꽌 꽔怨 諛곗뼇븯硫 洹좎뿉꽌 遺꾨퉬릺뒗 carbapenemase媛 meropenem쓣 鍮꾪솢꽦솕(inactivation)븯뒗 썝由щ 씠슜븳떎. Meropenem 뵒뒪겕 洹좎븸쓣 Tryptic soy broth (TSB)뿉 꽔怨 3떆媛 諛곗뼇븳 썑 E. coli ATCC 25922 (meropenem뿉 媛먯닔꽦)濡 뵒뒪겕 솗궛踰뺤쓣 떆뻾븳떎. 留뚯빟뿉 洹좎<뿉 carbapenemase媛 議댁옱븯硫 meropenem 뵒뒪겕媛 鍮꾪솢꽦솕릺뼱 뼲젣쓽 吏곴꼍씠 媛먯냼(6~15 mm)븯怨 슚냼媛 議댁옱븯吏 븡쑝硫 뼲젣 吏곴꼍 蹂븿씠 뾾嫄곕굹 16 mm 씠긽씠 맂떎(CLSI, 2018) (Fig. 4 & 5). KPC, NDM, VIM, IMP, IMI, SPM, SME 諛 OXA-type쓽 寃異쒖뿉 븳 삁誘쇰룄 諛 듅씠룄뒗 99%濡 븣젮졇 엳떎. 씠 諛⑸쾿 떆뻾븯湲 媛꾪렪븯硫 TSB 媛숈 media 씠쇅뿉 떆빟씠 븘슂 뾾뒗 옣젏씠 엳쑝굹 븯猷삳갇 룞븞 諛곗뼇쓣 빐빞 븯硫 Class A, B, D瑜 媛먮퀎븷 닔 뾾떎(van der Zwaluw et al., 2015).

Fig. 4. The modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM). Opening the black box of phenotypic carbapenemase detection. Serine carbapenemase is Class A 棺-lactamase such as KPC and GES. Metallo-棺-lactamase is Class B 棺-lactamase such as NDM, IMP, VIM [CLSI, 2018].

Fig. 5. The flowchart of interpretation of modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM). Opening the black box of phenotypic carbapenemase detection. mCIM is used for detecting carbapenemase in Enterobacterales whereas eCIM is used together with mCIM to differentiate metallo-棺-lactamse (Class B) from serine carbapenemase (Class A) [CLSI, 2018].

3) Carba NP test

꽭洹좎쓽 異붿텧臾쇱뿉 엳뒗 carbapenemase뿉 쓽빐 imipenem씠 媛닔遺꾪빐릺뒗 寃껋쓣 寃異쒗븯뒗 諛⑸쾿쑝濡 imipenem씠 媛닔遺꾪빐릺硫 pH媛 蹂솕릺怨 씠뼱꽌 pH 吏떆옄(phenol red)쓽 깋쓣 蹂솕떆궓떎. CLSI 吏移⑥꽌뿉 옄꽭븳 諛⑸쾿씠 湲곗닠릺뼱 엳떎(CLSI, 2018). 씠 諛⑸쾿 옣궡꽭洹좉낵 Pseudomonas spp. 紐⑤몢뿉꽌 슦닔븳 삁誘쇰룄 듅씠룄瑜 蹂댁뿬二쇱留 GES (Class A) OXA-48 (Class D)쓽 寃異쒖꽦쟻 醫뗭 븡떎. Carba NP 寃궗뒗 졃븯怨, 寃곌낵媛 鍮좊Ⅴ硫 떆뻾怨쇱젙怨 뙋룆씠 슜씠븯뿬 CPE 寃異쒖뿉 媛移섍 겕떎(Nordmann et al., 2012). 쁽옱 Rosco Diagnostica뿉꽌 Carba NP test뿉 븳 떆빟씠 긽뭹솕릺뼱 怨듦툒릺怨 엳떎.

4) Class A, B, D carbapenemase 媛먮퀎 諛⑸쾿(Differential test of carbapenemase)

Class A Class C carbapenemase뒗 boronic acid뿉 뼲젣릺怨, Class B (MBL)뒗 EDTA 삉뒗 dipicolinic acid뿉 뼲젣릺誘濡 meropenem 뵒뒪겕 씠뱾 뼲젣젣瑜 씠슜븳 씠以묐뵒뒪겕 긽듅 寃궗(double disk synergy test, DDST) 삉뒗 combined disk test瑜 떆뻾븯硫 class A, B, D 벑쓣 媛먮퀎븷 닔 엳떎(Stuart and Leverstein-Van Hall, 2010) (Table 2). 븳렪 mCIM 寃궗뿉 뼇꽦씤 洹좎 EDTA瑜 泥④븯뿬(eCIM) 媛숈 諛⑹떇쑝濡 寃궗븯硫 Class B (MBL)쓽 寃쎌슦 EDTA媛 Zn2+쓣 chelating븯뿬 carbapenemase瑜 鍮꾪솢꽦솕븯誘濡 뼲젣 吏곴꼍씠 利앷(mCIM 뼲젣 吏곴꼍怨 5 mm 씠긽 李⑥씠)븷 닔 엳떎(CLSI, 2018) (Fig. 4 & 5). Carba NP II test뒗 Carba NP test瑜 蹂삎븳 寃껋쑝濡 Carba NP Solution B뿉 tazobactam (Class A carbapenemase inhibitor) EDTA (Class B carbapenemase inhibitor)瑜 泥④븳 떆뿕愿(珥 4媛쒖쓽 떆뿕愿)쓣 씠슜븯뿬 class A, B, D瑜 援щ퀎븯뒗 寃궗씠떎(Dortet et al., 2012).

Interpretation chart of phenotypic carbapenemase confirmation tests

Confirmation test Carbapenemase AmpC with porin loss ESBL with porin loss
Class A Class B Class D
Modified Hodge test + + + -/+ -/+
Meropenem 짹 boronic acid + - - +/- -
Meropenem 짹 cloxacillin - - - +/- -
Imipenem 짹 EDTA - + - - -
Meropenem 짹 DPA - + - - -

Abbreviations: EDTA, ethylene diamine tetra-acetic acid; DPA, dipicolinic acid



湲고 class A (KPC) class B (MBL) carbapenemase瑜 寃異쒗븯뒗뜲 gradient MIC strips (eg, E-test)씠 궗슜맂떎. KPC gradient MIC strips (Etest KPC, bioM챕rieux, LaBalme-es-Grottes, France) KPC쓽 솢꽦쓣 뼲젣븯뒗 PBA (phenylboronic acid)瑜 븳履쎌쓽 carbapenem strip뿉留 泥④븳 썑 뼇履쎌쓽 carbapenem MIC瑜 痢≪젙븯뒗 諛⑸쾿씠떎. PBA瑜 泥④븳 carbapenem쓽 MIC媛 泥④븯吏 븡 MIC 蹂대떎 媛먯냼(MIC ratio媛 8諛 씠긽 媛먯냼븷 븣)븯硫 KPC瑜 깮꽦븯뒗 洹좎<濡 뙋떒븷 닔 엳떎. 씠諛⑸쾿쓽 KPC 寃異 삁誘쇰룄 듅씠룄媛 媛곴컖 92% 100%濡 蹂닿퀬릺怨 엳떎(Girlich et al., 2013). 鍮꾩듂븳 썝由щ줈 MBL gradient MIC strips뿉뒗 MBL 솢꽦쓣 뼲젣븯뒗 EDTA 삉뒗 dipicolinic acid瑜 궗슜븯뿬 MBL쓣 寃異쒗븯뒗뜲 씠슜븯怨 엳쑝硫, KPC gradient MIC strip怨 鍮꾩듂븳 꽦뒫쓣 蹂댁씤떎.

5) Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)

MALDI-TOF MS뒗 꽭洹좎쓽 吏꾨떒뿉 留ㅼ슦 쟻빀븯硫, 理쒓렐뿉 carbapenemase瑜 寃異쒗븯젮뒗 留롮 뿰援ш 吏꾪뻾릺怨 엳떎. Carbapenem 뵒뒪겕 寃궗븯젮뒗 洹좎쓣 1-2떆媛 諛곗뼇븳 썑 carbapenem 遺꾪빐 궛臾쇱쓽 뒪럺듃읆쓣 寃異쒗븯嫄곕굹, peak쓽 媛먯냼 삉뒗 쐞移섏쓽 蹂솕瑜 蹂닿퀬 吏꾨떒븯뒗 諛⑸쾿씠떎(Johansson et al., 2014) (Fig. 6). 씠 諛⑸쾿 듅씠룄媛 100% 젙룄씠굹 OXA-48쓽 寃異쒕쪧씠 궙븘 쟾泥댁쟻쑝濡 77%쓽 삁誘쇰룄瑜 蹂댁씤떎怨 蹂닿퀬릺怨 엳떎. MALDI-TOF MS 諛⑸쾿 븘吏곴퉴吏 쟾臾몄쟻씤 궗슜옄(expert user)뿉 젣븳릺뿀쑝硫 몴以솕릺吏 븡븘 꼸由 씠슜릺吏 븡吏留 젙솗븯怨 寃異쒖떆媛꾩씠 留ㅼ슦 吏㏃븘 븵쑝濡 carbapenemase쓽 寃異쒖뿉 以묒슂븳 뿭븷쓣 븷 寃껋쑝濡 湲곕맂떎.

Fig. 6. Mass spectrum showing the non hydrolysed pattern of ertapenem (A), the full hydrolysis of ertapenem of a KPC producing K. pneumoniae after 15 min (B) and the effect of the supplement of APBA inhibiting the KPC mediated hydrolysis of ertapenem (C) (Johansson et al., 2014; BMC Microbiol).

6) 遺꾩옄쑀쟾 寃궗(Molecular test)

쁽옱源뚯 二쇱슂 CPE 쑀쟾옄뿉뒗 KPC, NDM, VIM, IMP, OXA-48, GES 벑씠 엳쑝硫 媛곴컖쓽 CPE 쑀쟾옄瑜 利앺룺븯뿬 寃異쒗븯뒗 PCR怨 룞떆뿉 뿬윭 CPE 쑀쟾옄瑜 寃궗븷 닔 엳뒗 multiplex PCR 벑씠 냼媛쒕릺怨 엳떎(Monteiro et al., 2012). 理쒓렐뿉뒗 二쇱슂븳 CPE 쑀쟾삎씤 KPC, NDM, VIM, IMP, OXA-48쓣 룞떆뿉 寃異쒗븷 닔 엳뒗 긽뭹솕맂 multiplex PCR (Gene Xpert, BD-MAX 벑)怨 microarray (Biofire, Verigene)媛 援궡뿉 냼媛쒕릺뼱 씠슜릺怨 엳떎(Dod챕mont et al., 2014). 씠 諛⑸쾿 carbapenemase뿉 븳 specific gene쓣 寃異쒗븯湲 븣臾몄뿉 寃궗떆媛꾩씠 鍮좊Ⅴ怨, 寃곌낵媛 삁誘쇳븯怨 젙솗븳 寃궗씠굹, 젙빐吏 쑀쟾옄 쇅뿉 깉濡쒖슫 寃껋쓣 寃異쒗븯吏 紐삵븯뒗 떒젏씠 엳쑝硫, 긽뭹솕맂 寃껋 怨좉씠뼱꽌 寃궗쓽 젒洹쇱씠 뼱젮슱 닔 엳떎. 洹 쇅 寃궗踰뺤뿉 쟾옣泥 뿼湲곗꽌뿴遺꾩꽍(whole-genome sequencing) 諛⑸쾿씠 엳쑝굹 씠뒗 二쇰줈 carbapenem 궡꽦 湲곗쟾쓣 뿰援ы븯뒗뜲 씠슜븯硫, 떒닚엳 쑀쟾옄瑜 寃異쒗븯뒗 諛⑸쾿쑝濡쒕뒗 씠슜븯吏 븡뒗떎(Mathers et al., 2015). 吏湲덇퉴吏 湲곗닠븳 CPE쓽 寃異 諛⑸쾿쓽 꽦뒫怨 젣븳젏쓣 Table 3뿉 슂빟븯떎(Lutgring and Limbago, 2016) (Table 3).

Summary of detection methods for carbapenemase producing Enterobacterales

Tests method Accuracy TAT Detection Limitation Accessibility
Modified Hodge test Moderate Next day Carbapenemase activity Poor sensitivity for NDM High (LDT)
Poor specificity with AmpC*
mCIM High Next day Carbapenemase activity None known High (LDT)
Carba NP Moderate Next day Carbapenemase activity Poor sensitivity for OXA-48 Moderate (commercial)
Double disk synergy test High Next day Carbapenemase activity None known Moderate (LDT)
Gradient MIC strip
(E-test KPC or MBL)
Moderate Next day KPC or MBL Detects only KPC or MBL Moderate (commercial)
Poor specificity with AmpC
MALDI-TOF MS High Within day Carbapenemase activity None known Low-moderate
(LDT)
PCR (multiplex PCR, real-time PCR) High Within day Specific carbapenemase gene Unable to detect novel carbapenemase Low-moderate (commercial)
Microarray High Within day Specific carbapenemae gene Unable to detect novel carbapenemase Low-moderate (commercial)
Whole-genome sequencing High Several days Carbapenem resistance mechanism Unable to detect novel carbapenemase Low (LDT)

Abbreviations: TAT, turnaround time; mCIM, modified carbapenemase inactivation methods; LDT, laboratory developed test

aAccuracy: high, >90% sensitivity and specificity, moderate, 70~90% sensitivity and specificity; low, <70% sensitivity and specificity

bTurnaround time, time to results from pure culture of isolate

cAccessibility; High, all clinical microbiology laboratories could perform this test; moderate, advanced clinical microbiology laboratories could perform this test; low, reference laboratories could perform this test



7) 蹂닿퇏옄 寃궗(Screening of carriage)

CPE 蹂닿퇏옄쓽 쟻洹뱀쟻씤 꽑蹂꾧궗뒗 遺遺꾩쓽 蹂묒썝뿉꽌 씪긽쟻쑝濡 떆뻾릺吏 븡吏留 CPE 媛먯뿼쓽 諛쒖깮瑜좎씠 넂怨, 蹂묒썝 궡 쟾뙆媛 吏꾪뻾릺뒗 怨녹뿉꽌뒗 떆뻾븷 븘슂媛 엳떎. CPE 蹂닿퇏옄瑜 議곌린뿉 寃異쒗븯뒗 寃껋 CPE 媛먯뿼쓽 쟾뙆굹 젙李⑹쓣 留됯린 쐞빐 二쇨린쟻쑝濡 떆뻾븯뒗 寃껋씠 以묒슂븯떎(Doi and Paterson, 2015). 깉濡 諛쒓껄맂 蹂닿퇏옄 젒珥됲븳 옄, CPE 媛먯뿼쓽 諛쒖깮瑜좎씠 넂 蹂묒썝쑝濡 씠넚릺뒗 옄 洹몃━怨 CPE 媛먯뿼쓽 諛쒖깮瑜좎씠 넂 蹂묒썝쓽 以묓솚옄떎뿉 엯썝븯뒗 옄 벑뿉꽌 떆뻾븷 닔 엳떎. CPE 蹂닿퇏옄 寃궗뒗 吏곸옣룄留(rectal swab)쓣 씠슜븯硫, 梨꾩랬떆湲곕뒗 엯썝 2씪 씠궡 삉뒗 옱썝湲곌컙 룞븞 1二쇰쭏떎 洹몃━怨 쟾썝 삉뒗 눜썝 2씪 씠궡뿉 떆뻾븷 닔 엳떎. 寃궗踰뺤 MacConkey 븸泥대같吏뿉 carbapenem쓣 꽔怨 諛곗뼇 썑 寃異쒗븯뒗 諛⑸쾿(Landman et al., 2005), CHROM ID Carba 媛숈 CHROM 諛곗瑜 씠슜븯뒗 諛⑸쾿[CHROMagar, Paris, France], 寃泥댁뿉꽌 吏곸젒 PCR濡 寃異쒗븯뒗 諛⑸쾿 벑씠 냼媛쒕릺怨 엳떎(Vasoo et al., 2013). CHROM 諛곗뿉뒗 ChromID CARBA (KPC, VIM, NDM-1쓣 寃異) ChromID OXA-48 諛곗 벑씠 냼媛쒕릺怨 엳떎. 諛곗뼇踰뺤 鍮꾩슜씠 졃븯硫 寃궗媛 슜씠븯굹 솗吏 寃궗媛 븘슂븯硫 寃곌낵蹂닿퀬떆媛꾩씠 吏泥대맆 닔 엳떎. 遺꾩옄吏꾨떒踰뺤 떊냽븯怨 삁誘쇳븯硫 쑀쟾옄삎쓣 젣怨듯븷 닔 엳쑝굹 紐⑤뱺 CPE瑜 寃異쒗븷 닔 뾾쑝硫 怨좉씠떎.

3. Carbapenemase 깮꽦 洹좎<뿉 쓽븳 媛먯뿼쓽 移섎즺(Treatment of CPE)

옣궡꽭洹좎 삁븸留ㅺ컻 媛먯뿼, 룓졃, 諛 鍮꾨눊湲곌퀎 媛먯뿼 벑 떎뼇븳 醫낅쪟쓽 以묒쬆 媛먯뿼쓣 빞湲고븯뒗 쓷븳 꽭洹좎씠湲 븣臾몄뿉 씠뱾 洹좎뿉꽌 빆洹좎젣 궡꽦쓽 利앷뒗 移섎즺肉먮쭔 븘땲씪 궗쉶寃쎌젣쟻 쁺뼢씠 留ㅼ슦 겕떎(Rodr챠guez-Ba챰o et al., 2018). Carbapenemase뒗 carbapenem쓣 룷븿븯뒗 紐⑤뱺 棺-lactam 빆洹좎젣瑜 媛닔遺꾪빐븯誘濡 꽑깮븷 닔 엳뒗 빆깮젣뒗 留ㅼ슦 젣븳릺硫, 쑀쟾삎뿉 뵲씪 carbapenem쓣 떎뼇븳 젙룄濡 媛닔遺꾪빐 떆궎誘濡 CPE 媛먯뿼쓽 移섎즺뿉꽌 븯굹쓽 넻씪맂 移섎즺 諛⑸쾿씠 솗由쎈릺吏 븡븯떎. 洹몃윭굹 씪諛섏쟻쑝濡 븘옒쓽 3媛吏 諛⑸쾿뿉 븳 留롮 엫긽뿰援ш 떆뻾릺뿀怨 쁽옱뿉룄 吏꾪뻾 以묒씠떎. 1) Polymyxins (colistin or polymyxin B)怨 tigecycline씠 CPE 媛먯뿼쓽 1李 꽑깮빟쑝濡 媛꾩<릺吏留 씠뱾 빆洹좎젣 떒룆슂踰뺣낫떎 蹂묓빀슂踰뺤쓽 슚怨쇨 슦닔븯떎怨 븣젮졇 엳쑝硫, 2) carbapenem뿉 MIC媛 궙쓣 븣뒗 carbapenem룄 polymyxin씠굹 tigecycline怨 蹂묓빀쑝濡 궗슜맆 닔 엳떎. 3) 理쒓렐뿉뒗 깉濡쒖슫 棺-lactamase 뼲젣젣瑜 룷븿븯뒗 蹂듯빀젣媛 냼媛쒕릺怨 엳쑝硫 CPE type 蹂꾨줈 슚怨쇱뿉 李⑥씠媛 엳吏留 씠뱾 빆洹좎젣瑜 룷븿븯뿬 蹂묓빀슂踰뺤쓣 궗슜븯怨 엳떎. 쁽옱源뚯 CPE 媛먯뿼뿉 궗슜맆 닔 엳뒗 빆洹좎젣瑜 몴뿉 젙由ы븯떎(Rodr챠guez-Ba챰o et al., 2018) (Table 4).

Summary recommendations for specific antibiotics in treatment of carbapenemase producing Enterobacterales

Antibiotics Recommendation Effective CPE type
Polymyxins (including colistin) If meropenem MIC돞8 mg/L, combination therapy with meropenem KPC, NDM, OXA-48
If meropenem MIC>8 and 돞32 mg/L, combination with tigecycline or aminoglycosides etc
Tigecycline Combination therapy of MDR Enterobacteriaceae including CPE, use of higher dosing KPC, NDM, OXA-48
Fosfomycin Combination therapy of MDR Enterobacteriaceae including CPE, lower UTI KPC, NDM, OXA-48
Gentamicin Combination therapy of gentamicin-susceptible KPC-producing CPE KPC
Imipenem/meropenem If meropenem MIC돞8 mg/L, combination therapy with polymyxin KPC, NDM, OXA-48
Double carbapenem therapy: ertapenem and meropenem
Ceftazidime/avibactam Alone or combination with carbapenem or colistin in class A, D CPE KPC, OXA-48
Meropenem/vaborbactam Alone or combination with colistin or tigecycline in KPC KPC
Aztreonam/avibactam Combination with colistin or tigecycline in class B (MBL) NDM
Plazomicin Combination with colistin or tigecycline in KPC (not MBL) KPC
Ceftazidime OXA-48 producers are susceptible if not ESBL or AmpC producers OXA-48

(Rodr챠guez-Ba챰o et al., 2018)



1) KPC쓽 移섎즺

Polymyxin B, colistin, tigecycline, fosfomycin, selected aminoglycosides媛 移섎즺뿉 궗슜맆 닔 엳쑝硫, tigecycline, colistin, meropenem 벑쓽 蹂묓빀슂踰뺤씠 媛옣 쓷엳 궗슜맂떎.

(1) Colistin (polymyxin B)

Colistin fatty acid chain뿉 cationic cyclic polypeptide媛 뿰寃곕맂 援ъ“씠硫 colistin怨 polymyxin B뒗 븯굹쓽 븘誘몃끂궛留 떎瑜닿퀬 깮臾쇳븰쟻 솢꽦怨 꽭洹좎뿉 븳 궡洹좎꽦(bactericidal activity) 쑀궗븯떎. 옉슜 湲곗쟾 꽭洹좎쓽 쇅留(outer membrane)쓣 넻빐 씉닔릺뼱 lipopolysaccharide쓽 lipid A 寃고빀븯뿬 꽭洹좎쓣 궡洹좏븳떎(Bergen et al., 2012). 옣궡꽭洹 以 Proteus Providencia, Serratia 洹 醫낆 옄뿰 궡꽦씠硫 씠뱾 洹좎쓣 젣쇅븳 洹몃엺 쓬꽦 媛꾧퇏뿉 솢꽦쓣 蹂댁씤떎. Colistin 媛먯닔꽦씪 寃쎌슦 meropenem 蹂묓빀슂踰뺤쑝濡 궗슜릺怨 엳쑝硫 二쇰줈 젙留μ<궗瑜 넻빐 二쇱엯븳떎. 洹몃━怨 뇤泥숈닔븸뿉꽌뒗 移섎즺냽룄媛 룄떖븯吏 븡븘 뇤닔留됱뿼쓽 寃쎌슦뿉뒗 泥숈닔媛 궡(intrathecal)濡 吏곸젒 二쇱엯븳떎. 二쇱슂 遺옉슜쑝濡 떊룆꽦怨 떊寃쎈룆꽦씠 諛쒖깮븷 닔 엳怨, 遺遺꾩쓽 CPE뒗 colistin뿉 媛먯닔꽦씠굹 理쒓렐 colistin 궗슜쓽 利앷濡 씤빐 colistin 궡꽦 KPC 깮꽦 K. pneumoniae 벑씠 利앷븯怨 엳뒗 떎젙씠떎(Mammina et al., 2012). 듅엳 mcr-1씠씪뒗 쑀쟾옄瑜 룷븿븳 뵆씪뒪誘몃뱶媛 二쇱슂 궡꽦 썝씤쑝濡 蹂닿퀬릺怨 엳떎. NDM 삉뒗 OXA-48뿉꽌뒗 colistin 궡꽦씠 뱶臾쇰떎.

(2) Tigecycline

Minocycline쑝濡쒕꽣 쑀룄맂 빆洹좎젣濡 遺꾩옄웾쓣 利앷떆耳 쑀異(efflux)뿉 쓽븳 궡꽦 湲곗쟾쓣 슦쉶븯룄濡 留뚮뱾뿀쑝硫 aminoacyl-tRNA 긽샇옉슜쓣 留됱븘 떒諛깆쭏 빀꽦쓣 뼲젣븯뒗 湲곗쟾쓣 媛뽯뒗 빆洹좎젣씠떎. CPE瑜 룷븿븯뒗 洹몃엺 쓬꽦洹좉낵 뼇꽦洹좎뿉 愿묐쾾쐞븳 솢꽦쓣 媛吏怨 엳떎. Tigecycline 泥대궡뿉꽌 꼻寃 遺꾪룷븯뿬 삁븸씠굹 룓, 鍮꾨눊湲곌퀎쓽 냽룄媛 궙寃 쑀吏릺誘濡 洹좏삁利, 룓졃 諛 UTI뿉꽌 떒룆쑝濡 궗슜릺吏 븡怨 怨좊냽룄濡 떎瑜 빆洹좎젣 蹂묓빀븯뿬 궗슜맂떎(Barbour et al., 2009).

(3) Fosfomycin

UDP-N-acetylglucosamine-3 enolpyruvyl transferase瑜 遺덊솢꽦솕뿬 꽭洹좎쓽 꽭룷踰 깮꽦쓣 뼲젣븯뒗 빆洹좎젣濡 KPC 깮꽦 洹좎쓣 룷븿븯뿬 遺遺꾩쓽 CPE뿉 슚怨쇨 엳吏留 떒룆쑝濡 궗슜븯吏 븡怨 蹂묓빀슂踰뺤쑝濡 궗슜릺怨 엳떎(Falagas et al., 2010). 떒諛깆쭏 寃고빀씠 嫄곗쓽 뾾뒗 옉 遺꾩옄웾쑝濡 씤빐 궗援ъ껜 뿬怨쇱뿉 쓽빐 옒 젣嫄곕릺뼱 냼蹂뿉꽌 怨좊냽룄濡 냽異뺣릺誘濡 KPC瑜 룷븿븯뒗 CPE쓽 鍮꾨눊湲곌퀎 媛먯뿼쓽 移섎즺뿉 쓷엳 씠슜맂떎. Colistin怨 留덉갔媛吏濡 fosA3 쑀쟾옄瑜 룷븿븯뒗 뵆씪뒪誘몃뱶媛 궡꽦쓣 씪쑝궗 닔 엳떎.

(4) Aminoglycosides

媛먯닔꽦씤 aminoglycoside媛 떒룆 삉뒗 蹂묓빀슂踰뺤쑝濡 궗슜맆 닔 엳떎. Gentamicin씠 KPC 깮꽦 K. pneumoniae 媛먯뿼쓽 移섎즺뿉 궗슜맆 닔 엳떎. 듅엳 ST258 겢濡좎뿉 gentamicin 媛먯닔꽦씠 쑀吏릺怨 엳쑝硫(Naparstek et al., 2014) 떒룆쑝濡쒕뒗 궗슜븯吏 븡怨 蹂묓빀슂踰뺤쑝濡 궗슜릺뼱빞 븳떎. NDM 깮꽦 옣궡꽭洹좎뿉뒗 16S-ribosomal RNA methyl-transferase씠 쓷엳 議댁옱븯湲 븣臾몄뿉 궗슜씠 沅뚯옣릺吏 븡뒗떎. 理쒓렐뿉 plazomicin씠 媛쒕컻릺뿀쑝硫 KPC 깮꽦 K. pneumoniae뿉 쓽誘 엳뒗 솢꽦씠 엳쓬씠 蹂닿퀬 릺뿀떎. 洹몃윭굹 씠 빆洹좎젣룄 NDM뿉꽌뒗 궗슜씠 沅뚯옣릺吏 븡뒗떎.

(5) Carbapenems

CPE뒗 carbapenem뿉 떎뼇븳 理쒖냼뼲젣냽룄(MIC) (0.12 mg/L to >256 mg/L)瑜 蹂댁씪 닔 엳떎. Carbapenem뿉 븳 MIC媛 4 mg/L 씠븯씪 寃쎌슦 怨좊냽룄쓽 meropenem쓣 뜑 삤옯룞븞 궗슜븯硫 異⑸텇엳 궡洹좊냽룄뿉 룄떖븷 닔 엳떎怨 븣젮졇 엳떎. 洹몃윭굹 遺遺꾩쓽 CPE뒗 MIC媛 씠蹂대떎 넂븘 carbapenem 떒룆궗슜 沅뚯옣릺吏 븡뒗떎. KPC삎 K. pneumoniae뿉꽌 듅씠븯寃 몢 媛쒖쓽 carbapenem씠 蹂묓빀슂踰뺤쑝濡 궗슜릺湲곕룄 븯뒗뜲, ertapenem씠 KPC 슚냼뿉 넂 移쒗솕룄媛 엳뼱 KPC뿉 寃고빀븯뿬 誘몃겮뿭븷쓣 븯怨, 씠뼱 meropenem씠 penicillin binding protein뿉 寃고빀븯룄濡 븳떎뒗 썝由ъ씠떎(Tzouvelekis et al., 2012). 洹몃윭굹 씪諛섏쟻쑝濡 carbapenem 쐞뿉 湲곗닠븳 1李 꽑깮빟怨 蹂묓빀슂踰뺤쑝濡 궗슜맂떎.

(6) Ceftazidime-Avibactam

Avibactam class B 棺-lactamase (NDM, VIM, IMP)쓣 젣쇅븳 遺遺꾩쓽 棺-lactamase뿉 솢꽦쓣 蹂댁씠뒗 깉濡쒖슫 棺-lactamase 뼲젣씠떎. 뵲씪꽌 ceftazidime-avibactam KPC type (class A)怨 OXA-48 (class D) CPE뿉 솢꽦쓣 媛뽰쑝硫, NDM삎 CPE뿉뒗 솢꽦씠 뾾떎. 쁽옱 씠 빆洹좎젣뒗 Class A Class D CPE쓽 蹂묓빀슂踰뺤쑝濡 궗슜맆 닔 엳쑝硫 쁽옱 엫긽떆뿕 以묒뿉 엳떎(Castanheira et al., 2014).

(7) Meropenem-Vaborbactam

Vaborbactam KPC삎 CPE (Class A)瑜 뼲젣븯硫, MBL (Class B) OXA-48 (Class D)뒗 뼲젣븯吏 紐삵븯뒗 깉濡쒖슫 棺-lactamase 뼲젣젣씠떎. Meropenem-vaborbactam KPC삎 CPE뿉꽌 meropenem쓽 솢꽦쓣 蹂듭썝븯뿬 쑀吏븷 닔 엳寃 븯硫 쁽옱 FDA뿉 듅씤릺뼱 CPE뿉 쓽븳 鍮꾨눊깮떇怨 媛먯뿼뿉 궗슜릺怨 엳떎(Castanheira et al., 2016).

2) NDM쓽 移섎즺

MBL aztreonam쓣 젣쇅븳 紐⑤뱺 棺-lactam 빆깮젣뿉 궡꽦쓣 씪쑝궎吏留 MBL 깮꽦 洹좎<뒗 醫낆쥌 ESBL룄 룞떆뿉 깮꽦븯湲 븣臾몄뿉 aztreonam뿉룄 궡꽦씠떎. MBL 遺遺꾩쓽 棺-lactamase inhibitor뿉 뼲젣릺吏 븡吏留 avibactam ESBL쓣 遺덊솢꽦븯뿬 aztreonam쓣 솢꽦긽깭濡 쑀吏븯寃 븯뿬 aztreonam-avibactam쓽 蹂묓빀슂踰뺤 긽듅슚怨쇰 蹂댁씪 닔 엳떎怨 븣젮졇 엳떎(Wang et al., 2014). Colistin 媛먯닔꽦씪 寃쎌슦 rifampin-meropenem-colistin쓽 蹂묓빀룄 슚怨쇱쟻씠씪怨 蹂닿퀬릺怨 엳떎(T채ngd챕n et al., 2014). KPC삎怨 쑀궗븯寃 colistin怨 fosfomycin怨 蹂묓빀슂踰뺣룄 蹂닿퀬릺怨 엳떎.

3) OXA-48쓽 移섎즺

ESBL씠 뾾뒗 OXA-48 extended spectrum 棺-lactam 젣뿉 媛먯닔꽦씠硫 醫낆쥌 gentamicin 벑怨 媛숈 aminoglycoside뿉룄 媛먯닔꽦씠떎. Fosfomycin, imipenem, meropenem, tigecycline 벑쓽 蹂묓빀슂踰뺤씠 in vitro뿉꽌 슚怨쇰 蹂댁씤떎. KPC 쑀궗븯寃 colistin, tigecycline 벑怨 fosfomycin, carbapenem 湲고 媛먯닔꽦 빆洹좎젣쓽 蹂묓빀슂踰뺤씠 궗슜맆 닔 엳떎. 洹몃젃吏留 蹂묓빀슂踰뺤뿉룄 遺덇뎄븯怨 OXA-48뿉 쓽븳 삁븸留ㅺ컻 媛먯뿼쓽 삁썑뒗 留ㅼ슦 醫뗭 븡븘 궗留앸쪧씠 50%뿉 씠瑜몃떎怨 븣젮졇 엳떎(Navarro-San Francisco et al., 2013).

寃 濡

理쒓렐 쟾꽭怨꾩쟻쑝濡 carbapenem쓣 媛닔遺꾪빐븯뒗 슚냼瑜 깮꽦븯뒗 옣궡꽭洹(CPE)쓽 룺諛쒖쟻씤 利앷媛 떖媛곹븳 쐞삊씠 릺怨 엳떎. 蹂 뿰援ъ쓽 紐⑹쟻 CPE쓽 뿭븰, 寃異쒕갑踰 諛 移섎즺 諛⑸쾿쓽 理쒖꽑 룞뼢쓣 議곗궗븯뒗 寃껋씠떎. 꽭 媛吏 二쇱슂 carbapenemase 쑀삎씤 KPC, NDM, OXA삎씠 쟾꽭怨꾩쟻쑝濡 솗궛릺뼱 엳떎. KPC삎 誘멸뎅, 以묎뎅, 쑀읇 諛 씪떞븘硫붾━移댁뿉꽌 二쇰줈 寃異쒕릺硫, NDM삎 궓븘떆븘뿉꽌 二쇰줈 遺꾨━맂떎. OXA-48삎 吏以묓빐 遺곸븘봽由ъ뭅뿉꽌 쓷엳 蹂 닔 엳떎. 援궡뿉꽌 2015뀈遺꽣 CPE媛 룺諛쒖쟻쑝濡 利앷븯쑝硫, 2021뀈뿉 18,099二쇱쓽 CPE媛 遺꾨━릺뿀떎. Carbapenemase媛 遺꾨━맂 洹좎 K. pneumoniae, E. coli, E. cloacae 닚씠뿀떎. CPE 쑀쟾옄삎 KPC, NDM, OXA삎 닚쑝濡 遺꾪룷븯떎. CPE瑜 寃異쒗븯뒗 몴쁽삎 諛⑸쾿뿉뒗 carbapenem 遺꾪빐슚냼 寃異 諛⑸쾿(CIT)怨 CPE 醫낅쪟 媛먮퀎 寃궗媛 엳떎. CPT뿉뒗 modified Hodge 寃궗, modified carbapenem inactivation method (mCIM), Carba NP 寃궗 벑씠 엳쑝硫, 씠 以묒뿉 mCIM씠 젒洹쇱꽦怨 젙솗꽦씠 醫뗭븘 媛옣 꼸由 씠슜릺怨 엳떎. 鍮좊Ⅸ 寃곌낵瑜 뼸湲 쐞빐 留롮 쑀쟾삎 遺꾩꽍踰뺤씠 떆뻾릺怨 엳뒗뜲, 떎以 떎떆媛 PCR怨 microarray瑜 씠슜븳 긽슜솕맂 궎듃媛 꼸由 궗슜릺怨 엳떎. Colistin怨 tigecycline CPE 移섎즺쓽 1李 빟쑝濡 궗슜릺硫, meropenem, fosfomycin怨 媛숈 2李 移섎즺젣 蹂묒슜븯뿬 궗슜릺怨 엳떎.

ACKNOWLEDGEMENT

This work was supported by the National Research Foundation of Korea (NRF2021R1I1A1A01049073 to Y.H.B.).

CONFLICT OF INTEREST

The authors declare no conflict interest.

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