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Genetic Diversity of Metallo-β-lactamase Genes of Chryseobacterium indologenes Isolates from Korea
Biomed Sci Letters 2019;25:275-281
Published online September 30, 2019;  https://doi.org/10.15616/BSL.2019.25.3.275
© 2019 The Korean Society For Biomedical Laboratory Sciences.

Jong Hwa Yum†,*

Department of Clinical Laboratory Science, Dongeui University, Busan 47340, Korea
Correspondence to: Jong Hwa Yum. Department of Clinical Laboratory Science, Dongeui University, Busan 47340, Korea.
Tel: +82-51-890-2682, Fax: +82-505-182-6877, e-mail: auxotype@deu.ac.kr
*Professor.
Received August 15, 2019; Revised September 2, 2019; Accepted September 9, 2019.
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
This study was performed to characterize the chromosomal metallo-β-lactamases (MBLs) of Chryseobacterium indologenes isolated from Korea and to propose a clustering method of IND MBLs based on their amino acid similarities. Chromosomal MBL genes were amplified by PCR from 31 clinical isolates of E. indologenes. Nucleotide sequencing was performed by the dideoxy chain termination method using these PCR products. Antimicrobial susceptibilities were determined by the agar dilution method. PCR experiments showed that all 31 E. indologenes isolates contained all blaIND genes. DNA sequence analysis revealed that E. indologenes isolates possessed ten types of blaIND gene, including seven novel variants (blaIND-8 to blaIND-14). The most common combination of MBL was IND-2 (n = 18). Minimum inhibitory concentrations of imipenem and meropenem for the isolates harboring novel IND MBLs were ≥ 16 µg/mL. IND MBLs were grouped in three clusters, based on amino acid similarities.
Keywords : Chryseobacterium indologenes, Metallo-β-lactamase, IND, blaIND, Cluster
꽌 濡

Chryseobacterium indologenes뒗 臾쇱씠굹 넗뼇怨 媛숈 옄뿰뿉 쓷엳 遺꾪룷븯怨 엳吏留, C. indologenes뒗 썝궡媛먯뿼씠굹 湲고쉶媛먯뿼쓣 넻빐 떎뼇븳 엫긽 利앹긽쓣 굹궡뒗 寃껋쑝濡 븣젮졇 엳떎(Hsuh et al., 1997; Kirby et al., 2004; At캇c캇 et al., 2016; Rabenandrasana et al., 2019).

C. indologenes뒗 imipenem怨 meropenem怨 媛숈 carbapenem뿉 빐 궡꽦쓣 蹂댁씪 닔 엳뒗 metallo-β-lactamase (MBL)쓣 媛吏怨 엳뼱 遺遺꾩쓽 β-lactams 젣젣뿉 빐 궡꽦쓣 蹂댁씤떎(Bellais et al., 2000; Yu et al., 2015). 삉븳, C. indologenes뒗 쓷엳 떎빟젣 궡꽦쓣 蹂댁뿬 移섎즺 떆 빟젣꽑깮뿉 뼱젮씠 엳怨, 移섏궗쑉룄 14%뿉 떖븳떎(Hsueh et al., 1997; Douvoyiannis et al., 2010).

C. indologenes쓽 ambler class B MBL뿉 냽븯뒗 indologenease (IND)瑜 理쒖큹濡 봽옉뒪쓽 Bellais 벑씠 蹂닿퀬븯怨 (Bellais et al., 1999), 씠썑, 2000뀈뿉 Bellais 벑씠 엫긽뿉꽌 遺꾨━븳 C. indologenes뿉꽌 blaIND-1~4瑜 寃異쒗븯뿬 蹂닿퀬븯떎(Bellais et al., 2000). 2008뀈뿉뒗 以묎뎅뿉꽌 Lin 벑씠 1,500 蹂묒긽 븰蹂묒썝뿉꽌 遺꾨━ 洹좎<뿉꽌 寃異쒗븳 blaIND-1~3쓣 蹂닿퀬븳 諛 엳怨, 遺遺꾩씠 imipenem怨 meropenem뿉 넂 빆洹좎젣 理쒖냼뼲젣냽룄(Minimal inhibitory concentration; MIC)瑜 蹂댁떎(Lin et al., 2008). 씠깭由ъ쓽 Perilli 벑 2007뀈 pI. 8.8쓽 IND-5瑜 蹂닿퀬븯떎(Perilli et al., 2007). 2009뀈 씠깭由ъ쓽 삉떎瑜 蹂묒썝뿉꽌 寃異쒕맂 IND-6瑜 Zeba 벑씠 寃異쒗븯뒗뜲, ceftazidime怨 cefepime쓣 옒 遺꾪빐븯吏 紐삵븯뒗 IND-2 IND-5뒗 떖由 떎뼇븳 β-lactamase 젣젣瑜 鍮꾧탳쟻 슚쑉쟻쑝濡 遺꾪빐븯떎(Zeba et al., 2009). 2010뀈 씪蹂몄뿉꽌 Yamaguchi 벑 IND-7쓣 寃異쒗븯怨, 씠 슚냼쓽 X-ray뿉 쓽븳 遺꾩옄援ъ“瑜 諛앺삍떎(Yamaguchi et al., 2010). 엫긽뿉꽌 遺꾨━릺뒗 C. indologenes쓽 뿼깋泥댁꽦 blaIND뒗 떆湲곗 吏뿭뿉 뵲씪 떎뼇븳 듅꽦쓣 蹂댁씠硫 寃異쒕릺뒗 寃껋쓣 븣 닔 엳떎. 뵲씪꽌 蹂 뿰援ъ뿉꽌뒗 援궡 븰蹂묒썝 솚옄濡쒕꽣 遺꾨━맂 C. indologenes쓽 MBL쓽 醫낅쪟 쑀쟾옄 듅꽦쓣 洹쒕챸븯怨좎옄 븯떎.

옱猷 諛 諛⑸쾿

떆뿕 洹좎<

떊珥뚯꽭釉뚮뒪蹂묒썝怨 媛쒓툑諛깅퀝썝뿉꽌 1994뀈遺꽣 2009뀈源뚯 遺꾨━맂 C. indologenes 31二쇰 긽쑝濡 븯쑝硫, 洹좎쥌 룞젙 쟾넻쟻 諛⑸쾿怨 16S rDNA쓽 뿼湲곗꽌뿴 遺꾩꽍쓣 씠슜븯떎(Loffler et al., 2000). 蹂 뿰援ъ뿉꽌 궗슜븳 엫긽 遺꾨━ 洹좎<뒗 20% skim milk뿉 遺쑀븯뿬 -70°C뿉 蹂닿븯뿬 떆뿕븯떎. Escherichia coli ATCC 25922 Pseudomonas aeruginosa ATCC 27853쓣 빆洹좎젣 理쒖냼뼲젣냽룄떆뿕뿉 李몄“ 洹좎<濡 궗슜븯떎.

빆洹좎젣 媛먯닔꽦 떆뿕

빆洹좎젣 媛먯닔꽦 떆뿕 CLSI (Clinical and Laboratory Standards Institute, 2017)쓽 沅뚭퀬뿉 뵲씪 104 colony forming units쓽 젒醫낆븸쓣 Mueller-Hinton agar (Becton Dickinson, Sparks, MD., USA)뿉 젒醫낇븯뿬 怨좎껜븳泥쒗씗꽍踰뺤쑝濡 寃곗젙븯떎. 떆뿕뿉 궗슜븳 빆洹좎젣뒗 amoxicillin (Kun Wha Pharmaceuticals, Seoul, Korea), piperacillin (Wyeth, Pearl River, NY, USA), cephalothin (Sigma Chemical Co., St. Louis, USA), ceftazidime (GlaxoSmithKline, Greenford, UK), cefotaxime (Handok, Seoul, Korea), cefoxitin怨 imipenem (Merck Sharp & Dohme, Rahway, NJ., USA), aztreonam怨 cefepime (Bristol-Myers Squibb, Plainsboro, NJ., USA), moxalactam (Eli Lilly & Co., Indianapolis, IN., USA), 洹몃━怨 meropenem (Sumitomo, Tokyo, Japan) 씠뿀떎.

MBL 몴쁽삎 寃異

MBL 깮꽦 洹좎< MBL 鍮꾩깮꽦 洹좎<瑜 援щ퀎븯湲 쐞빐 Lee 벑씠 蹂닿퀬븳 諛⑸쾿쑝濡 Hodge 蹂踰뺢낵 imipenem-EDTA 蹂踰 + sodium mercaptopropionic acid (SMA) double disc synergy (DDS) 떆뿕쓣 떆뻾븯떎(Lee et al., 2004).

遺꾩옄깮臾쇳븰쟻 遺꾩꽍

뿼깋泥 쑀옒 IND MBL쓣 븫샇솕븯뒗 쑀쟾옄 寃異쒖 Table 1뿉 湲곗닠븳 떆諛쒖껜瑜 씠슜븯뿬 PCR 利앺룺쓣 떆뻾븯떎. PCR preMIX taq polymerase (Bioneer, Cheongwon, Korea), 媛곴컖쓽 떆諛쒖껜뒗 20 pmol, 뿴뿉 쓽빐 異붿텧맂 二쇳삎 DNA 1 μL瑜 泥④븯怨, 理쒖쥌 뼇쓣 100 μL濡 議곗젙븯뿬 떆뻾븯떎. PCR 諛섏쓳 議곌굔 94°C 5遺꾧컙 二쇳삎 DNA瑜 denature떆궎怨, 씠썑 94°C 30珥, 50°C 30珥, 72°C 60珥덈줈 35쉶 諛섏쓳븯怨, 留덉留 72°C 7遺꾧컙 extension 諛섏쓳븯떎. PCR 깮꽦臾쇱 뿼湲곗꽌뿴 遺꾩꽍븯떎. 紐⑤뱺 PCR 깮꽦臾 뼇媛떏 automatic sequencer (ABI3700: Perkin-Elmer, Foster City, CA., USA)濡 2쉶 뿼湲곗꽌뿴 遺꾩꽍븯떎. blaIND 쑀쟾옄쓽 open reading frame (ORF)쓽 5’ 3’ 留먮떒 뿼湲곗꽌뿴 Sørensen 벑씠 젣떆븳 諛⑸쾿怨 媛숈씠 simple two-step PCR濡 떆뻾븯떎(Sørensen et al., 1993). 씠뱾 MBL쓽 븘誘몃끂궛 꽌뿴 봽濡쒓렇옩 CLUSTAL X version 2.0 (ftp://ftp-igbmc.ustrasbg.fr/pub/clustalx)濡 遺꾩옄깮臾쇳븰쟻 쑀뿰愿怨꾨 遺꾩꽍븯떎.

The primers used for detection or sequencing

 Primer 5’-to-3’sequence Product size (bp) Reference
INDD-F 5’-GCC CAG GTT AAA GAT TTT GTA AT-3’ 628 Steinberg et al., 2005
INDD-R 5’-CAT GGC CAC CGC CTT TCC ATT C-3’

INDS-F 5’-GGT TTG CAT ATC TAT CTG CC-3’ 955 This study
INDS-R 5’-ATC CAA AGA GAG GCT GGA GT-3’

N1INDS-F 5’-CTT TAA TTA CTA CCT TAA AAA TT-3’ 802 This study
N1INDS-R 5’-AAT ACA AAT CCC GGA TGA C-3’

NN2INDS-F 5’-TTT AAT TAT TAC CCT AAA AAT T-3’ 845 Used for sequencing This study
NN2INDS-R 5’-AAA TCC CGA ATT TTC ATT CG-3’
N2IND-seq-R 5’-CCC AGG GAA CAT CAA ACA G-3’

N3INDS-F 5’-AAC TTT AAT TAC TGC TTT AAA TT-3’ 850 This study
N3INDS-R 5’-TTT CAA TAC TGC GGA AGA G-3’

16SRNA-F 5’-AGA GTT TGA TCC TGG CTC AG-3’ 1,544 Loffler et al., 2000
16SRNA-R 5’-AAG GAG GTG ATC CAG CCG CA-3’


Nucleotide sequence accession numbers

蹂 뿰援ъ뿉꽌 諛앺엺 깉濡쒖슫 blaIND 뿼湲곗꽌뿴 GenBank nucleotide database뿉 떎쓬쓽 accession number濡 벑濡앺븯떎. GU186042 (blaIND-2c), GU186043 (blaIND-7), GU186044 (blaIND-8), GU186045.1 (blaIND-9), GU206353 (blaIND-10), HM2455379 (blaIND-11), HM2455380 (blaIND-12), HM2455381 (blaIND-13), HM367709 (blaIND-14).

寃 怨

엫긽遺꾨━二 듅꽦

엫긽뿉꽌 遺꾨━맂 imipenem 궡꽦 C. indologenes 31二 紐⑤몢뒗 Hodge 蹂踰뺢낵 imipenem-EDTA+SMA DDS 떆뿕 뼇꽦쑝濡 MBL 깮꽦二쇱씠뿀떎. 씠뱾 MBL 깮꽦 C. indologenes 31二 以 22二쇨 媛앸떞뿉꽌 遺꾨━릺뼱 媛옣 留롮븯怨, 씠뱾 솚옄뒗 二쇰줈 硫댁뿭븯 솚옄씠뿀쑝硫, 31紐 以 7紐낆씠 궗留앺븯떎(Table 2). 떎쓬쑝濡 MBL 깮꽦 C. indologenes媛 留롮씠 遺꾨━맂 寃泥대뒗 삁븸쑝濡 4二쇨 遺꾨━릺뿀쑝硫, 洹 쇅 寃泥댁뿉꽌뒗 5二쇨 遺꾨━릺뿀떎.

Clinical characteristics of specimens with isolates of C. indologenes in Korean hospitals

Strains No. Specimen blaIND Underlying disease
YMC94/01/3047 Sputum blalND-7 Cervical cord tumor
YMC94/04/3376 Sputum blaIND-8 Cerebral infarction
YMC94/12/3839 Sputum blalND-7 Aspiration pneumonia
YMC96/09/3073 Sputum blalND-9 Subdural hematoma
YMC96/09/3300 Sputum blalND-9 Oropharyngeal abscess
YMC03/04/833 Urine blaIND-2b Tuberculous spondylitis
YMC03/04/558 Sputum blaIND-2 Venococclusive disease
DEUIJM04-066 Sputum blaIND-2c Pulmonary tuberculosis preterm infants
DEUIJM05-0117 Blood blalND-10 Aplastic anemia
DEUIJM05-0267 Sputum blalND-2a Pulmonary embolism
DEUIJM05-0416 Sputum blaIND-2 Atherosclerosis
DEUIJM05-0540 Blood blaIND-2c Lung cancer
DEUIJM05-0759 Sputum blaIND-2a Pulmonary tuberculosis preterm infants
DEUIJM06-1048 Blood blaIND-2c Viral encephalitis
DEUIJM07-0523 Cerebrospinal fluid blaIND-2 Intracerebral hemorrhage
DEUUM08-0001 Blood blalND-11 Parkinson’s disease
DEUIJM08-0899 Cerebrospinal fluid blalND-13 Encephalomyelitis
DEUIJM08-1666 Sputum blaIND-2c Liver cirrhosis
DEUIJM08-1667 Sputum blaIND-2c Cerebral infarction
DEUIJM08-1754 Sputum blaIND-13 Pulmonary tuberculosis preterm infants
DEUIJM09-0544 Sputum blaIND-2c Intracerebral hemorrhage
DEUIJM09-0587 Bronchial washing blaIND-2c Bacterial pneumonia
DEUIJM09-0659 Sputum blalND-2c Cerebral infarction
DEUIJM09-0687 Sputum blaIND-2c Lung cancer
DEUIJM09-0753 Sputum blaIND-2c Subarachnoid hemorrhage
DEUIJM09-0922 Sputum blaIND-14 Mitral stenosis
DEUIJM09-1280 Sputum blaIND-2b Klatskin tumor
DEUIJM09-1409 Sputum blalND-2b Preterm infants
DEUIJM09-1419 Catheter tip blalND-2b Preterm infants
DEUIJM09-1499 Sputum blaiND-2b Preterm infants
DEUIJM09-1534 Sputum blaIND-12 Extreme immaturity


Metallo-β-lactamase쓽 쑀쟾삎

엫긽뿉꽌 遺꾨━맂 31二 C. indologenes 紐⑤몢뒗 MBL쓣 깮꽦븯떎. 紐⑤뱺 C. indologenes 遺꾨━二쇰뒗 PCR뿉 쓽빐 IND瑜 븫샇솕븯뒗 쑀쟾옄媛 寃異쒕릺뿀떎. C. indologenes 遺꾨━二쇰뒗 DNA 뿼湲곗꽌뿴 遺꾩꽍뿉꽌 깉濡 諛앺吏 7醫낆쓽 깉濡쒖슫 蹂씠醫(blaIND-8뿉꽌 blaIND-14源뚯)쓣 룷븿븯뿬 8醫낆쓽 IND 쑀쟾삎쓣 굹깉떎(Table 2). C. indologenes 31二 以 IND-2瑜 깮꽦븯뒗 洹좎<뒗 18二쇰줈 媛옣 쓷븯怨, 9二쇱뿉꽌 깉濡쒖슫 blaIND alleles媛 寃異쒕릺뿀떎.

Metallo-β-lactamase쓽 쑀쟾쟻 쑀뿰愿怨

Phylogenic 뿰援ъ뿉꽌 13醫낆쓽 IND 슚냼뒗 븘誘몃끂궛 꽌뿴뿉 뵲瑜 쑀궗룄瑜 洹쇨굅濡 3媛吏 cluster濡 洹몃9吏뼱吏뒗 寃껋쑝濡 굹궗떎(Fig. 1). Bellais 벑(Bellais et al., 2000)씠 봽옉뒪뿉꽌 泥섏쓬 蹂닿퀬븳 IND-4瑜 젣쇅븳 IND-1 type怨 IND-2 type쓽 cluster뒗 媛곴컖 쑀쟾쟻쑝濡 媛源뚯슫 寃껋쑝濡 蹂댁씤떎. 븳렪, 蹂 뿰援ъ뿉꽌 떆뿕븳 洹좎<쓽 IND 10醫낆쓽 쑀쟾삎 2媛吏쓽 cluster뿉 냽븯떎. 씠뱾 以 IND-11~13 湲곗〈뿉 蹂닿퀬맂 떎瑜 IND 븘誘몃끂궛 꽌뿴씠 떎냼 李⑥씠媛 엳뼱 IND-2 븿猿 떎瑜 cluster濡 遺꾨쪟릺뿀떎(Fig. 1). C. indologenes 9二쇱쓽 IND 븘誘몃끂궛 꽌뿴쓽 alignment瑜 떆뻾븳 寃곌낵 73~100%쓽 identity瑜 蹂댁떎.

Fig. 1.

Dendrogram obtained for 14 representative INDs calculated with CLUSTALX version 2.0. The red circle () indicates novel IND enzymes



IND-1 cluster뿉뒗 IND-3, IND-5, IND-6, IND-7, IND-8, IND-9, IND-10, 洹몃━怨 IND-14 슚냼媛 룷븿맂떎(Fig. 1). IND-2 cluster뿉뒗 IND-11, IND-12, 洹몃━怨 IND-13 슚냼媛 룷븿맂떎. IND-4 cluster뒗 IND-1 cluster IND-2 cluster뒗 吏꾪솕쟻쑝濡 쑀뿰愿怨꾧 癒 寃껋쑝濡 굹궗怨, 깉濡쒖슫 IND濡 諛앺吏 IND-11, IND-12, 洹몃━怨 IND-13媛꾩뿉뒗 쑀뿰愿怨꾧 媛源뚯슫 寃껋쑝濡 굹궗떎.

Class B β-lactamases뿉 븳 standard numbering scheme뿉 뵲瑜, Zn1쓽 ligand濡 삁긽릺뒗 His116, His118, 洹몃━怨 His196쓽 븘誘몃끂궛 옍湲곗 Zn2쓽 ligand濡 삁긽릺뒗 Asp120, Cys221, 洹몃━怨 His263쓽 븘誘몃끂궛 옍湲곕뒗 7醫낆쓽 깉濡쒖슫 IND 슚냼뿉꽌룄 옒 蹂댁〈릺뼱 엳뿀떎(Fig. 2).

Fig. 2.

Comparison of amino acid sequence of the IND β-lactamase from C. indologenes isolates. The hyphen (-) indicates identical amino acid sequence. The asterisk (*) and cross (+) indicate the residues known to be involved either directly or indirectly with Zn1 and Zn2 cofactors, respectively.



빆洹좎젣 媛먯닔꽦 떆뿕

β-lactam 젣쓽 MIC뒗 piperacillin, ceftazidime 諛 cefepime쓣 젣쇅븯怨좊뒗 遺遺 鍮꾧탳쟻 넂븯뒗뜲, 씠뒗 Zeba 벑쓽(Zeba et al., 2009) 蹂닿퀬 鍮꾩듂븯떎(Table 3). Imipenem怨 meropenem MICs뒗 C. indologenes뿉 빐꽌 紐⑤몢 ≥ 16 μg/mL씠뿀怨, IND-9~12 깮꽦 洹좎<뒗 ceftazidime怨 cefepime쓽 MICs뒗 媛곴컖 ≥ 2 μg/mL怨 ≥ 0.5 μg/mL쑝濡 鍮꾧탳쟻 궙븯떎.

MICs of β-lactams for IND type β-lactamase-producing clinical isolates of C. indologenes in Korean hospitals

MBL types
(No. of isolates)
MIC range (μg/mL)a

IPM MEM AZT CEP CTX CAZ FEP MOX FOX PIP
IND-2 (18) 32~>128 16~>128 32~>128 >128 32~>128 4~64 4~128 32~128 8~128 4~>256
IND-7 (2) 16~32 32~64 32~64 >128 32 4~64 64~128 64~128 16 4~32
IND-8 (1) 64 32 32 >128 64 8 >128 128 32 32
IND-9 (2) 16~128 16~128 32 >128 32~>128 4~8 4 64 8~32 4~64
IND-10 (1) 64 16 16 >128 32 2 0.5 32 8 4
IND-11 (1) 32 16 64 >128 16 16 4 128 16 4
IND-12 (1) 32 16 64 >128 32 16 4 128 16 4
IND-13 (4) 32~64 16~32 64~>128 >128 32~64 4~32 16~>128 64~128 16 4~16
IND-14 (1) 32 16 64 >128 64 8 128 128 16 16

Total (31) 16~>128 16~>128 16~>128 >128 16~>128 2~64 0.5~>128 32~128 8~128 4~>256
IMP, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CAZ, ceftazidime; FEP, cefepime; CEP, cephalothin; MOX, moxalactam; FOX, cefoxitin; AMX, amoxicillin; PIP, piperacillin

怨 李

蹂 뿰援ш껐怨 援궡뿉꽌 遺꾨━맂 C. indologenes뒗 紐⑤몢 blaIND瑜 媛뽮퀬 엳뿀떎. 봽옉뒪쓽 Bellais 벑씠 1999뀈 泥섏쓬 蹂닿퀬븳 C. indologenes쓽 IND-1 씠썑濡 7醫낆쓽 IND 슚냼媛 蹂닿퀬릺뿀떎(Bellais et al., 1999; Bellais et al., 2000; Perilli et al., 2007; Lin et al., 2008; Zeba et al., 2009; Yamaguchi et al., 2010). 蹂 뿰援ъ뿉꽌뒗 援궡 3李 븰蹂묒썝뿉꽌 遺꾨━븳 C. indologenes뿉꽌 9醫낆쓽 IND瑜 寃異쒗뻽怨, 씠뱾 洹좎쥌뿉꽌 carbapenem 궡꽦뿉 愿뿬븷 寃껋쑝濡 삁긽릺뒗 깉濡쒖슫 7醫낆쓽 IND 슚냼瑜 媛뽯뒗 洹좎쥌뿉 빐 imipenem怨 meropenem쓽 MIC 媛믪씠 16 μg/mL 씠긽쑝濡 굹굹 씠뱾 洹좎< 紐⑤몢 궡꽦씠뿀떎.

C. indologenes 湲곗吏덊솚씠 엳뒗 硫댁뿭븯 솚옄뿉꽌 移섎챸쟻씤 媛먯뿼쓣 씪쑝궗 닔 엳뒗 寃껋쑝濡 븣젮졇 엳떎(Nulens et al., 2001; Lin et al., 2003; Bayraktar et al., 2007; Hossam et al., 2007; Douvoyiannis et al., 2010). 蹂 뿰援ъ뿉꽌룄 넂 移섏궗쑉쓣 蹂댁떎(23%, n = 7). C. indologenes 媛먯뿼떆 移섎즺 諛⑸쾿 떎뼇븯寃 븣젮졇 엳쑝굹, imipenem씠굹 meropenem怨 媛숈 carbapenem肉 븘땲씪 떎뼇븳 빆洹좎젣뿉 븳 궡꽦쓣 蹂댁씠뒗 씠뱾 媛먯뿼 移섎즺뿉 븘슂븳 吏移 솗由쎌씠 븘슂빐 蹂댁씤떎.

寃곕줎쟻쑝濡, 援궡 븰蹂묒썝뿉꽌 遺꾨━맂 C. indologenes뒗 紐⑤몢 blaIND瑜 媛뽮퀬 엳뿀怨, 씠뱾 以 9二쇰뒗 7媛吏쓽 깉濡쒖슫 blaIND瑜 媛뽮퀬 엳뿀떎. IND뒗 븘誘몃끂궛 꽌뿴쓽 쑀궗룄뿉 洹쇨굅빐 蹂 븣, 7醫낆쓽 깉濡쒖슫 蹂씠 슚냼瑜 룷븿빐꽌 3媛쒖쓽 cluster濡 굹돇硫, 씠뱾 쑀쟾옄瑜 媛吏 꽭洹좎 carbapenem 궗슜쓽 利앷濡 썝궡뿉꽌 젏李 利앷븷 寃껋쑝濡 뙋떒맂떎.

ACKNOWLEDGEMENT

洹좎< 닔吏묒뿉 룄쓣 二쇱떊 뿰꽭븰援 쓽怨쇰븰쓽 씠寃쎌썝 援먯닔떂怨 씤젣븰援 쓽怨쇰븰쓽 떊젙솚 援먯닔떂猿 媛먯궗 뱶由쎈땲떎.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

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