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Bae, Jeong, Lee, Yong, Lee, Hong, Kim, Park, Kang, Uh, Shin, Lee, Ahn, Lee, Woo, and Kwak: Emergence of CTX-M-12 and A Novel CTX-M Type Extended-Spectrum β-Lactamase-producing Klebsiella pneumoniae
Original Article

Korean J Leg Med 2006;26(1):21-26.

Published online: 10 February 2006

DOI: https://doi.org/10.3343/kjlm.2006.26.1.21

Emergence of CTX-M-12 and A Novel CTX-M Type Extended-Spectrum β-Lactamase-producing Klebsiella pneumoniae

Il Kwon Bae, M.D.1, Seok Hoon Jeong, M.D.1, Kyungwon Lee, M.D.2, Dongeun Yong, M.D.2, Jongwook Lee, M.D.3, Seong Geun Hong, M.D.4, Eui-Chong Kim, M.D.5, Yeon Jun Park, M.D.6, Jung Oak Kang, M.D.7, Young Uh, M.D.8, Jong Hee Shin, M.D.9, Wee Gyo Lee, M.D.10, Ji young Ahn, M.D.11, Sung-Hee Lee, M.D.12, Gun-Jo Woo, Ph.D13, Hyo-Sun Kwak, Ph.D.13

1Department of Laboratory Medicine, Kosin University College of Medicine, Busan, Korea

2Yonsei University College of Medicine, Seoul, Korea

3Keonyang University College of Medicine, Daejeon, Korea

4Pochon CHA University College of Medicine, Sungnam, Korea

5Seoul University College of Medicine, Seoul, Korea

6The Catholic University of Korea College of Medicine, Seoul, Korea

7Hanyang University College of Medicine, Guri, Korea

8Yonsei University Wonju University College of Medicine, Wonju, Korea

9Chonnam National University College of Medicine, Gwangju, Korea

10Ajou University College of Medicine, Suwon, Korea

11Sooncheonhyang University College of Medicine, Gumi, Korea

12Cheju Hanmaeum Hospital, Jeju, Korea

13Center for Food Safety Evaluation, Korea Food and Drug Administration, Seoul, Korea

Received 22 September 2005       Revised 21 November 2005       Accepted 6 February 2006

Copyright © 2006 The Korean Society for Legal Medicine

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

Background

The aims of this study were to survey the nation-wide susceptibilities of Klebsiella pneumoniae isolates against ceftazidime and cefotaxime and to determine the prevalence of class A extended-spectrum β-lactamases (ESBLs).

Methods

During the period of February to July 2004, K. pneumoniae isolates intermediate or resistant to ceftazidime and/or cefotaxime were collected from 12 hospitals in Korea. Antimicrobial susceptibilities were determined by the disk diffusion and the agar dilution methods and ESBL-production was by double-disk synergy test. Ceftazidime or cefotaxime-resistance determinants of the ESBL-producers were transfered to Escherichia coli J53 by transconjugation. Searches for class A ESBL genes were performed by PCR amplication.

Results

Among 212 clinical K. pneumoniae isolates, 172 (81%) isolates showed positive results in double-disk synergy test; the most prevalent ESBL was SHV-12 (n=104). Genes encoding ESBLs including SHV-2 (n=6), SHV-2a (n=17), CTX-M-3 (n=18), CTX-M-9 (n=6), CTX-M-12 (n=1), CTX-M-14 (n=27), CTX-M-15 (n=3), and a novel CTX-M-type β-lactamases were also detected.

Conclusions

It is concluded that diversity of ESBLs in K. pneumoniae isolates are increasing in Korea. CTX-M-12 has never been reported in Asia, and a novel CTX-M-type ESBL has emerged.

Keywords: Klebsiella pneumoniae, Class A ESBL

References

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Table 1.
Amino acid differences between CTX-M-1 β-lactamase and the related cefotaxime-hydrolyzing enzymes including CTX-M-3, CTX-M-12, CTX-M-15 and CTX-M-NEW
β-lactamase Residue at amino acid
 GenBank Accession No.
77 89 114 140 167 240 278 288
CTX-M-1 Val Asn Asp Ser Pro Asp Val Asn X92506
CTX-M-3 Ala Asn Asn Ala Pro Asp Val Asp Y10278
CTX-M-12 Ala Ser Asn Ala Pro Asp Ile Asp AF305837
CTX-M-15 Ala Asn Asn Ala Pro Gly Val Asp AY044436
New CTX-M Ala Asn Asn Ala Gln Asp Val Asp  

Abbreviations: Ala, alanine; Asn, asparagine; Asp, aspartic acid; Gln, glutamine; Ile, isoleucine; Pro, proline; Ser, serine.

Table 2.
Prevalence of class A ESBL-producing K. pneumoniae isolates in 2004
ESBL gene type Hospital (No. of double-disk synergy-positive isolates)
 Total (172)
SN (12) SS (16) SM (19) AJ (5) BD (18) HY (19) WK (17) KY (3) JN (17) SC (18) KS (20) JJ (8)
CTX-M-3 1 4 1     3         3   12
CTX-M-3+SHV-12     2   1 3             6
CTX-M-9                     3   3
CTX-M-9+SHV-2a 1                       1
CTX-M-9+SHV-12 1         1             2
CTX-M-12           1             1
CTX-M-14 1   1 3     3   2       10
CTX-M-14+SHV-2                 6       6
CTX-M-14+SHV-2a 1                       1
CTX-M-14+SHV-12             9 1         10
CTX-M-15     1     1             2
CTX-M-15+SHV-12           1             1
CTX-M-NEW+SHV-2a         1               1
SHV-2a 1 1   1 3 1     1   6   14
SHV-12 6 10 13   8 5 5 1 8 16 7 6 85
TEM-52                   1 1   2

Abbreviations: SN, Seoul A; SS, Seoul B; SM, Seoul C; AJ, Suwon; BD, Seongnam; HY, Guri; WK, Wonju; KY, Daejeon; JN, Gwangju; SC, Gumi; KS, Busan; JJ, Jeju.

Table 3.
Characteristics of Ambler class A ESBL-producing K. pneumoniae isolates
Type of Ambler class A ESBLs No. (%) of isolates MIC (μg/mL)
FOX
 ATM
 CAZ
 CAZ/CLA
 CTX
 CTX/CLA
 PIPM
Range MIC50 Range MIC50 Range MIC50 Range MIC50 Range MIC50 Range MIC50 Range MIC50
CTX-M-3 12 (5.7) 2–256 8 8->256 32 2–64 8 2–64 4 32–256 64 1–256 32 0.06–1 0.25
CTX-M-3+SHV-12 6 (2.8) 4–256   128->256   128->256   32–256   32->256   32–256   0.12–2  
CTX-M-9 3 (1.4) 4   8   1   0.5–1   32   2–4   0.25  
CTX-M-9+SHV-2a 1 (0.5) 2   8   8   8   16   8   0.12  
CTX-M-9+SHV-12 2 (0.9) 4–16   128->256   128->256   16–128   8–32   8–16   0.12–0.25  
CTX-M-12 1 (0.5) 32   32   16   16   32   32   0.25  
CTX-M-14 10 (4.7) 2->256   2->256   0.5–256   0.25–128   8–128   8–128   0.12–0.25  
CTX-M-14+SHV-2 6 (2.8) 8–64   32–64   16–32   8–32   32–64   32–64   0.12–0.25  
CTX-M-14+SHV-2a 1 (0.5) 8   16   8   16   32   32   0.12  
CTX-M-14+SHV-12 10 (4.7) 16->256   256->256   128–256   64–128   32–256   64–256   0.12–4  
CTX-M-15 2 (0.9) 4–8   >256   256->256   64–128   >256   128   0.25–2  
CTX-M-15+SHV-12 1 (0.5) 256   >256   >256   256   >256   128   0.25  
CTX-M-NEW+SHV-2a 1 (0.5) 8   4   128   64   4   1   0.12  
SHV-2a 14 (6.6) 2->256 16 2->256 32 4->256 32 8–256 16 8–256 32 0.5–256 8 0.12–16 0.5
SHV-12 85 (40.1) 2->256 256 2->256 256 32->256 >256 4->256 64 4->256 32 0.25->256 8 0.06–4 0.25
TEM-52 2 (0.9) 4   32   64   16–32   128   4–16   0.12–0.5  

* Clavulanic acid at a fixed concentration of 4 μg/mL.

Abbreviations: See Table 2.

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