Differences in Antimicrobial Resistance Phenotypes by the Group of CTX-M Extended-Spectrum β-Lactamase

Bareum Gwon12   Eun-Jeong  Yoon*2   Dokyun Kim  Kim2   Hyukmin  Lee2   Jong Hee  Shin3   Jeong Hwan  Shin4   Kyeong Seob  Shin5   Young Ah  Kim6   Young Uh7   Young Ree  Kim9   Hyun Soo  Kim8   Seok Hoon  Jeong2   

1 Department of Clinical Pathology, Sangji University College of Science, Wonju
2 Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul
3 Department of Laboratory Medicine, Chonnam National University School of Medicine, Gwangju
4 Department of Laboratory Medicine, Inje University Busan Paik Hospital, Busan,
5 Department of Laboratory Medicine,College of Medicine, Chungbuk National University, Cheongju,
6 Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital, Goyang
7 Department of Laboratory Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju
8 Department of Laboratory Medicine,Hallym University College of Medicine, Hwaseong
9 Department of Laboratory Medicine, School of Medicine,Jeju National University, Jeju,

* Corresponding author: Tel: +82-2-2019-3783, Fax: +82-2-2019-3784, E-mail: ejyoon@yuhs.ac


Background: Escherichia coli and Klebsiellapneumoniae clinical isolates producing CTX-M extendedspectrum β-lactamases (ESBLs) were assessed for antimicrobial resistance phenotypes varied by group of enzymes.

Methods: A total of 1,338 blood isolates, including 959 E. coli and 379 K.pneumoniae, were studied. All the strains were collected between January and July 2017 from eight general hospitals in South Korea. The species were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined by disk diffusion methods and ESBL phenotypes by double-disk synergy tests using disks containing cefotaxime, ceftazidime, cefepime, aztreonam, and clavulanic acid (CA). The genes for β-lactamases were identified by PCR and sequencing.

Results: Of total microbes, 31.6% (303/959) E. coli and 24.0% (91/379) K.pneumoniae were resistant to cefotaxime and 28.1% (269/959) E. coli and 20.1% (76/379) K.pneumoniae were CTX-M-type ESBL producers. Among the detected CTX-M ESBLs, 58.0% (156/269) in E. coli and 86.8% (66/76) in K. pneumoniae belonged to group 1, 46.8% (126/269) in E. coli and 14.5% (11/76) in K.pneumoniae were group 9. Ten E. coli and one K.pneumoniae isolates co-produced both groups of CTX-M ESBL. The group 1 CTX-M producers had a higher level of resistance to cefotaxime, ceftazidime, cefepime, and aztreonam and exhibited stronger synergistic activities when combined with CA compared to group 9.

Conclusion: ESBL phenotypes differ by CTX-M ESBL group and phenotype testing with drugs including 4th generation cephalosporins and monobactams is critical for screening CTX-M-producers with better sensitivity. (Ann Clin Microbiol 2019;22:1-8)


This research was supported by a fund (2017E4400100#) from the Research Program of Korea Centers for Disease Control and Prevention.

Figures & Tables

Fig. 1. Zone diameter of the four drugs (A and C) and the synergy with clavulanic acid (SC) (B and D) by bacterial species (A and B) and by groups of CTX-M (C and D). A total of 269 E. coli (ECO) and 76 K.pneumoniae (KPN) CTX-M producers (A and B) including 211 group 1 CTX-M producers and 123 group 9 CTX-M producers (C and D) were plotted. Boxplots present the 1 and 3 quartiles with whiskers showing either the maximum and minimum values. The thick horizontal line indicates median values, black lines for E. coli or group 1 CTX-M and gray lines for K.pneumoniae or group 9 CTX-M ESBL producers. The SC value was calculated by dividing the enlarged zone diameter near the CA disk by inhibition zone diameter of each drug. The statistical significance was calculated using Pearson’s chi-square test [16] by using SPSS statistics (version 23, IBM Corp., Armonk, NY, USA) and the significance (P) was indicated by using asterisks: **P<0.01; *P<0.05.