Annals of Clinical Microbiology, The official Journal of the Korean Society of Clinical Microbiology

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Four genotypes of carbapenem-resistant Acinetobacter baumannii strains lacking OXA-23 production in Korea

Brief communication

Kim YA, Jeong SH, Shin JH, et al. Four genotypes of carbapenem-resistant Acinetobacter baumannii strains lacking OXA-23 production in Korea. Ann Clin Microbiol 2024;27:143-147.

Annals of Clinical Microbiology (Ann Clin Microbiol) 2024 June, Volume 27, Issue 2, pages 143-147. https://doi.org/10.5145/ACM.2024.27.2.8

Received on 16 April 2024, Revised on 31 May 2024, Accepted on 12 June 2024, Published on 20 June 2024.

Four genotypes of carbapenem-resistant Acinetobacter baumannii strains lacking OXA-23 production in Korea

1Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital, Goyang, 2Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, 3Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, 4Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, 5Department of Laboratory Medicine, Chungbuk National University College of Medicine, Cheongju, 6Department of Laboratory Medicine and Paik Institute for Clinical Research, Inje University College of Medicine, Busan, 7Department of Laboratory Medicine, Jeju National University, College of Medicine, Jeju, 8Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, 9Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, 10Department of Laboratory Medicine, Keimyung University School of Medicine, Daegu, Korea

Corresponding author: Young Ah Kim, E-mail: yakim@nhimc.or.kr

Abstract

During nationwide Fantimicrobial surveillance (Korea Global Antimicrobial Resistance Surveillance System [Kor-GLASS]), the recent emergence of non-oxacillinase (OXA)-23 production by carbapenem-resistant Acinetobacter baumannii (CRAB) isolates was noted. In this study, we evaluated resistance mechanisms other than OXA-23 production to elucidate the shift in considerable CRAB clones. The presence of OXA carbapenemase genes, such as blaOXA-23blaOXA-24blaOXA-58, and blaOXA-51-ISAba1, was determined by PCR. Other carbapenemase genes, such as blaIMPblaVIMblaNDMblaKPCblaGES, and blaOXA-48 , were determined using sequencing. Strains lacking carbapenemase genes were subjected to whole genome sequencing, and resistance genes were analyzed using ResFinder. Four CRAB strains were collected through a Kor-GLASS study in 2022, in which OXA-23 production was not identified. The carbapenemase genotypes of the four CRAB strains lacking blaOXA-23 were blaOXA-51-ISAba1blaOXA-66/ACD25blaOXA-182, and blaNDM-1. To the best of our knowledge, this is the f irst study to identify CRAB producing New Delhi metallo-β-lactamase (NDM)-1 in Korea. In conclusion, domestic CRAB resistance mechanisms may undergo subtle changes. Continuous observations are required to monitor the emergence of new clones.

Keywords

Carbapenem, Resistance, Acinetobacter baumannii, NDM-1, OXA-23

Acinetobacter baumannii is an important pathogen that causes healthcare-associated infections, such as ventilator-associated pneumonia, line-associated bloodstream infections, and catheter-associated urinary tract infections [1]. Carbapenem is usually considered a treatment option for extended-spectrum ß-lactamase producers. The rapid increase in carbapenem-resistant A. baumannii (CRAB) isolation has been correlated with an increased nationwide prescription rate of carbapenems [2]. The carbapenem resistance rate is very high in strains isolated in Korea, and multidrug resistance is common, hindering the selection of therapeutic options [3]. According to Kor-GLASS (Korea Global Antimicrobial Resistance Surveillance System) data, the imipenem-resistance rate of A. baumannii blood isolates was > 90% [3].

There are three classes of carbapenemase: Ambler class A (serine carbapenemases), class B (metallo-βlactamase), and class D (oxacillinase carbapenemases) [4]. Klebsiella pneumoniae carbapenemase (class A), New Delhi metallo-β-lactamase (NDM, class B), and oxacillinase-48 (class D) are common in carbapenemresistant Enterobacteriaceae [5]. Metallo-β-lactamases, such as Guiana extended-spectrum β-lactamase, imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), and NDM, are frequently found in carbapenem-resistant Pseudomonas aeruginosa [6].

Carbapenemase types in carbapenem-resistant organisms other than A. baumannii vary. However, CRAB isolates uniformly carry blaOXA-23 in Korea because of the notorious multidrug resistance clone, A. baumannii global clone 2 with sequencing type 191, which has become predominant in clinical settings worldwide, including Korea [7]. OXA-type β-lactamases are the primary resistance mechanism for CRAB, and a drastic increase in A. baumannii isolates with blaOXA-23 has been observed since the mid-2000s [7]. ISAba1associated blaOXA-51, another contributor to CRAB, has decreased since the mid-2000s [7].

The recent emergence of non-OXA-23 production of CRAB isolates was noted in a Kor-GLASS study. Therefore, in the present study, resistance mechanisms other than OXA-23 production were evaluated to elucidate the shift in significant CRAB clones.

In total, 366 A. baumannii isolates were collected according to the Kor-GLASS protocol in 2022 [8]. A. baumannii strains were identified using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (Bruker Biotyper; Bruker Daltonics GmbH), and positive OXA-51 polymerase chain reaction (PCR) results confirmed the species identification. PCR methods determined the existence of OXA carbapenemase genes, such as blaOXA-23, blaOXA-24, blaOXA-58, and blaOXA-51-ISAba1 [8]. PCR sequencing methods also determined the presence of other carbapenemase genes, such as blaIMP, blaVIM, blaNDM, blaKPC, blaGES, and blaOXA-48 [8]. Strains without determination of carbapenemase genes using the aforementioned methods were subjected to whole genome sequencing, as previously described [9]. Using the NextSeq 550 instrument (Illumina), the entire genome was sequenced with 8 μg of input genomic DNA. Sequences were assembled using Spades (version 3.11.1) and annotated using Prokka (version 1.13.7). Resistance genes were determined using ResFinder 4.5 [10].

The resistance rate to imipenem was 85.2% in A. baumannii isolates in 2022, and 98.7% in OXA-24 producers. The carbapenemase genotypes of the four CRAB strains lacking blaOXA-23 were blaOXA-66/ACD-25, blaOXA-51-ISAba1, blaOXA-182, and blaNDM-1 (Table 1).

Table 1. Distribution of imipenem resistance in 366 A. baumannii isolates (2022)

Imipenem susceptibilityGenotypesNo. (%)
Resistant312 (85.2)
OXA-23308 (98.7)
Non-OXA-23004 (1.3)
blaOXA-66/ACD-25001 (0.3)
blaOXA-51-ISAba1001 (0.3)
blaOXA-182001 (0.3)
blaNDM-1001 (0.3)
Susceptible054 (14.8)
Total366 (100)

ISAba1-mediated intrinsic blaADC-25 and blaOXA-66 overexpression has been reported in South Korea [11,12].
The carbapenem resistance mechanism of blaOXA-182 has also been reported in Korea [13]. In this report, when 178 imipenem-non-susceptible A. baumannii isolates were collected from 12 Korean hospitals in 2007, 12 isolates from a Jeju Island hospital produced OXA-182 carbapenemase, which showed 93% identity with OXA-143 and 89% with OXA-40 [13].

To our knowledge, this is the first report of NDM-1 producing A. baumannii being detected. NDM1 is one of the metallo-ß-lactamases (MBL), which originated in India and spread worldwide, especially in Enterobacteriaceae [5]. However, MBL production is sporadic in CRAB in Korea, and the few reports on MBL types include VIM-2, SIM-1, and IMP-1 [14,15]. Recently, the dissemination of NDM-1 in A. baumannii strains has been reported in China [16,17]; however, to the best of our knowledge, this is the first report of NDM-1-producing A. baumannii.

In conclusion, the mechanism of resistance via OXA-23 in CRAB may have subtly changed with the emergence of NDM-1-producing A. baumannii in Korea. Continuous observation is required to monitor the emergence of new clones.

Ethics statement

This study was approved by the Institutional Review Board of the National Health Insurance Ilsan Hospital (No. 2024-05-016), and the requirement for informed consent was waived.

Conflicts of interest

Jeong Hwan Shin is an associate editor and Young Uh and Nam Hee Ryoo are editorial board members of the Annals of Clinical Microbiology. However, they were not involved in the review process of this article. No other potential conflict of interest relevant to this article was reported.

Funding

This study was funded by a grant from the Korean Society of Clinical Microbiology (2023).

The research was supported by a fund (2020E540600) from the Research Program of Korean Disease Control and Prevention Agency.

References

1. Kim YJ, Kim SI, Kim YR, Hong KW, Wie SH, Park YJ, et al. Carbapenem-resistant Acinetobacter baumannii: diversity of resistant mechanisms and risk factors for infection. Epidemiol Infect 2012;140:137-45.  

2. Kim YA, Park YS, Youk T, Lee H, Lee K. Abrupt increase in rate of imipenem resistance in Acinetobacter baumannii complex strains isolated from general hospitals in Korea and correlation with carbapenem administration during 2002-2013. Ann Lab Med 2018;38:179-81.   

3. Kim D, Yoon EJ, Hong JS, Choi MH, Kim HS, Kim YR, et al. Major bloodstream infectioncausing bacterial pathogens and their antimicrobial resistance in South Korea, 2017-2019: phase I report from Kor-GLASS. Front Microbiol 2022;12:799084.   

4. Kim YA and Park YS. Epidemiology and treatment of antimicrobial resistant gram-negative bacteria in Korea. Korean J Intern Med 2018;33:247-55.   

5. Jeong H, Hyun J, Lee Y. Characteristics of carbapenem-resistant Enterobacteriaceae (CRE) in the Republic of Korea, 2021. Public Health Wkly Rep 2022;15:2354-63.

6. Choi YJ, Kim YA, Kim J, Jeong SH, Shin JH, Shin KS, et al. Emergence of NDM-1-producing Pseudomonas aeruginosa sequence type 773 clone: shift of carbapenemase molecular epidemiology and spread of 16S rRNA methylase genes in Korea. Ann Lab Med 2023;43:1969.    

7. Lee Y, D’Souza R, Yong D, Lee K. Prediction of putative resistance islands in a carbapenemresistant Acinetobacter baumannii global clone 2 clinical isolate. Ann Lab Med 2016;36:320-4.   

8. Lee H, Yoon EJ, Kim D, Jeong SH, Shin JH, Shin JH, et al. Establishment of the South Korean national antimicrobial resistance surveillance system, Kor-GLASS, in 2016. Euro Surveill 2018;23:1700734.   

9. Heo J, Choi YJ, Kim YA, Jeong SH, Shin JH, Shin KS, et al. Current prevalence of the crpP gene in carbapenemase-producing Pseudomonas aeruginosa blood isolates in Korea. Ann Clin Microbiol 2022;25:53-9. 

10. Center for Genomic Epidemiology. https://www.genomicepidemiology.org/ [Online] (last visited on 2 April 2024).

11. Kim S, Park YJ, Kim J. Inverse PCR for subtyping of Acinetobacter baumannii carrying ISAba1. J Microbiol 2016;54:376-80.  

12. Yoon EJ, Kim HS, Woo H, Choi YJ, Won D, Choi JR, et al. Trajectory of genetic alterations associated with colistin resistance in Acinetobacter baumannii during an in-hospital outbreak of infection. J Antimicrob Chemother 2021;77:69-73.  

13. Kim CK, Lee Y, Lee H, Woo GJ, Song W, Kim MN, et al. Prevalence and diversity of carbapenemases among imipenem-nonsusceptible Acinetobacter isolates in Korea: emergence of a novel OXA-182. Diagn Microbiol Infect Dis 2010;68:432-8.  

14. Lee K, Yum JH, Yong D, Lee HM, Kim HD, Docquier JD, et al. Novel acquired metallo-betalactamase gene, blaSIM-1, in a class 1 integron from Acinetobacter baumannii clinical isolates from Korea. Antimicrob Agents Chemother 2005;49:4485-91.   

15. Sung JY, Kwon KC, Park JW, Kim YS, Kim JM, Shin KS, et al. Dissemination of IMP-1 and OXA type beta-lactamase in carbapenem-resistant Acinetobacter baumannii. Korean J Lab Med 2008;28:16-23.  

16. Liu N, Zheng X, Zhu Q, He Z, Hu S. The dissemination of NDM-1 in Acinetobacter baumannii strains. Curr Microbiol 2022;79:117.  

17. Liu H, Moran RA, Chen Y, Doughty EL, Hua X, Jiang Y, et al. Transferable Acinetobacter baumannii plasmid pDETAB2 encodes OXA-58 and NDM-1 and represents a new class of antibiotic resistance plasmids. J Antimicrob Chemother 2021;76:1130-4.  

Table 1

1. Kim YJ, Kim SI, Kim YR, Hong KW, Wie SH, Park YJ, et al. Carbapenem-resistant Acinetobacter baumannii: diversity of resistant mechanisms and risk factors for infection. Epidemiol Infect 2012;140:137-45.

2. Kim YA, Park YS, Youk T, Lee H, Lee K. Abrupt increase in rate of imipenem resistance in Acinetobacter baumannii complex strains isolated from general hospitals in Korea and correlation with carbapenem administration during 2002-2013. Ann Lab Med 2018;38:179-81.

3. Kim D, Yoon EJ, Hong JS, Choi MH, Kim HS, Kim YR, et al. Major bloodstream infectioncausing bacterial pathogens and their antimicrobial resistance in South Korea, 2017-2019: phase I report from Kor-GLASS. Front Microbiol 2022;12:799084.

4. Kim YA and Park YS. Epidemiology and treatment of antimicrobial resistant gram-negative bacteria in Korea. Korean J Intern Med 2018;33:247-55.

5. Jeong H, Hyun J, Lee Y. Characteristics of carbapenem-resistant Enterobacteriaceae (CRE) in the Republic of Korea, 2021. Public Health Wkly Rep 2022;15:2354-63.

6. Choi YJ, Kim YA, Kim J, Jeong SH, Shin JH, Shin KS, et al. Emergence of NDM-1-producing Pseudomonas aeruginosa sequence type 773 clone: shift of carbapenemase molecular epidemiology and spread of 16S rRNA methylase genes in Korea. Ann Lab Med 2023;43:1969.

7. Lee Y, D’Souza R, Yong D, Lee K. Prediction of putative resistance islands in a carbapenemresistant Acinetobacter baumannii global clone 2 clinical isolate. Ann Lab Med 2016;36:320-4.

8. Lee H, Yoon EJ, Kim D, Jeong SH, Shin JH, Shin JH, et al. Establishment of the South Korean national antimicrobial resistance surveillance system, Kor-GLASS, in 2016. Euro Surveill 2018;23:1700734.

9. Heo J, Choi YJ, Kim YA, Jeong SH, Shin JH, Shin KS, et al. Current prevalence of the crpP gene in carbapenemase-producing Pseudomonas aeruginosa blood isolates in Korea. Ann Clin Microbiol 2022;25:53-9.

10. Center for Genomic Epidemiology. https://www.genomicepidemiology.org/ [Online] (last visited on 2 April 2024).

11. Kim S, Park YJ, Kim J. Inverse PCR for subtyping of Acinetobacter baumannii carrying ISAba1. J Microbiol 2016;54:376-80.

12. Yoon EJ, Kim HS, Woo H, Choi YJ, Won D, Choi JR, et al. Trajectory of genetic alterations associated with colistin resistance in Acinetobacter baumannii during an in-hospital outbreak of infection. J Antimicrob Chemother 2021;77:69-73.

13. Kim CK, Lee Y, Lee H, Woo GJ, Song W, Kim MN, et al. Prevalence and diversity of carbapenemases among imipenem-nonsusceptible Acinetobacter isolates in Korea: emergence of a novel OXA-182. Diagn Microbiol Infect Dis 2010;68:432-8.

14. Lee K, Yum JH, Yong D, Lee HM, Kim HD, Docquier JD, et al. Novel acquired metallo-betalactamase gene, blaSIM-1, in a class 1 integron from Acinetobacter baumannii clinical isolates from Korea. Antimicrob Agents Chemother 2005;49:4485-91.

15. Sung JY, Kwon KC, Park JW, Kim YS, Kim JM, Shin KS, et al. Dissemination of IMP-1 and OXA type beta-lactamase in carbapenem-resistant Acinetobacter baumannii. Korean J Lab Med 2008;28:16-23.

16. Liu N, Zheng X, Zhu Q, He Z, Hu S. The dissemination of NDM-1 in Acinetobacter baumannii strains. Curr Microbiol 2022;79:117.

17. Liu H, Moran RA, Chen Y, Doughty EL, Hua X, Jiang Y, et al. Transferable Acinetobacter baumannii plasmid pDETAB2 encodes OXA-58 and NDM-1 and represents a new class of antibiotic resistance plasmids. J Antimicrob Chemother 2021;76:1130-4.