Prevalence of blaOXA genes in carbapenem-resistant Acinetobacter baumannii isolates from clinical specimens from Nopparatrajathanee Hospital

Sawanya Pongparit; Adun Bunchaleamchai; Naiyana Watthanakul; Nonthawat Boonma; Kothchakron Massarotti; Supreeya Khamuan; Nutchodchapan Ingkasamphan; Kansini Wannasin

Authors

Sawanya Pongparit Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand
Adun Bunchaleamchai Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand
Naiyana Watthanakul Department of Pathology (Microbiology), Nopparatrajathanee Hospital, Bangkok 10230, Thailand
Nonthawat Boonma Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand
Kothchakron Massarotti Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand
Supreeya Khamuan Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand
Nutchodchapan Ingkasamphan Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand
Kansini Wannasin Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand

Keywords:

carbapenem-resistant Acinetobacter baumannii, extensively drug-resistant, ISAba1-blaOXA-51-like gene, OXA-type carbapenemase genes

Abstract

This study aimed to investigate the prevalence of bla_OXA genes in carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from Nopparatrajathanee Hospital and the resistance rate against antimicrobial agents used for A. baumannii treatment. The susceptibility of 170 CRAB isolates, obtained from July to October 2018 at Nopparatrajathanee Hospital, was tested against seven antimicrobial agents by the disk diffusion method. While the susceptibility to colistin was determined by the broth microdilution method. The distribution of carbapenem-resistant genes of bla_OXA-51-like, bla_OXA-23-like, bla_OXA-58-like, and bla_OXA-24-like in the CRAB isolates was determined using a multiplex polymerase chain reaction. The MBL-type carbapenemase genes and ISAba1-bla_OXA-51-likegene in the CRAB isolates were also detected using conventional PCR. The majority of CRABs (99.42%) were non-susceptible to more than three antimicrobials categories, and 31.18% of CRABs were extensively drug-resistant. Most CRAB isolates (99.42%) were non-susceptible to more than three categories of antimicrobial agents, and 31.18% of CRAB were extensively drug-resistant. Although colistin and tigecycline were the two most effective antimicrobial agents, the resistance rates were 7.06% and 4.12%, respectively. All isolates had the intrinsic resistance gene of A. baumannii, the bla_OXA-51-likegene. The frequencies of bla_OXA-51-likewith bla_OXA-23-like;bla_OXA-51-likewith bla_OXA-24-like; bla_OXA-51-likewith bla_OXA-23-likeand bla_OXA-58-like; and ISAba1-bla_OXA-51-likewere 77.06%, 4.71%, 3.53%, and 14.12%, respectively. None of the isolates were positive for MBL-type carbapenemase genes. This research showed that the dominant carbapenems resistance gene among the CRAB in this hospital was bla_OXA-23-like. It also confirmed the horror of drug resistance problems for A. baumannii with limited treatment options, which should raise everyone's awareness.

References

Alexopoulou, K., Foka, A., Petinaki, E., Jelastopulu, E., Dimitracopoulos, G., & Spiliopoulou, I. (2006). Comparison of two commercial methods with PCR restriction fragment length polymorphism of the tuf gene in the identification of coagulase-negative staphylococci. Letters in Applied Microbiology, 43(4), 450-454. DOI: https://doi.org/10.1111/j.1472-765X.2006.01964.

Bou, G., Cerveró, G., Domínguez, M. A., Quereda, C., & Martínez-Beltrán, J. (2000). Characterization of a nosocomial outbreak caused by a multiresistant Acinetobacter baumannii strain with a carbapenem-hydrolyzing enzyme: high-level carbapenem resistance in A. baumannii is not due solely to the presence of beta-lactamases. Journal of Clinical Microbiology, 38(9), 3299-3305. DOI: https://doi.org/10.1128/JCM.38.9.3299-3305.2000

Chen, C. H., Kuo, H. Y., Hsu, P. J., Chang, C. M., Chen, J. Y., Lu, H. H. S., ... & Liou, M. L. (2018). Clonal spread of carbapenem-resistant Acinetobacter baumannii across a community hospital and its affiliated long-term care facilities: A cross sectional study. Journal of Microbiology, Immunology and Infection, 51(3), 377-384. DOI: https://doi.org/10.1016/j.jmii.2017.08.001

Clinical and Laboratory Standards Institute guidelines (CLSI). (2018). Performance Standards for Antimicrobial Susceptibility Testing, (28th ed.). Clinical and Laboratory Standards Institute.

Cornejo-Juárez, P., Cevallos, M. A., Castro-Jaimes, S., Castillo-Ramírez, S., Velázquez-Acosta, C., Martínez-Oliva, D., ... & Volkow-Fernández, P. (2020). High mortality in an outbreak of multidrug resistant Acinetobacter baumannii infection introduced to an oncological hospital by a patient transferred from a general hospital. PLOS ONE, 15(7), e0234684. DOI: https://doi.org/10.1371/journal.pone.

Doi, Y. (2019). Treatment options for carbapenem-resistant Gram-negative bacterial infections. Clinical Infectious Diseases, 69(Supplement_7), S565-S575. DOI: https://doi.org/10.1093/cid/ciz830

Evans, B. A., & Amyes, S. G. B. (2014). OXA β-lactamases. Clinical Microbiology Reviews, 27(2), 241-263. DOI: https://doi.org/10.1128/CMR.00117-13

Hrenovic, J., Durn, G., Goic-Barisic, I., & Kovacic, A. (2014). Occurrence of an environmental Acinetobacter baumannii strain similar to a clinical isolate in Paleosol from Croatia. Applied and Environmental Microbiology, 80(9), 2860-2866. DOI: https://doi.org/10.1128/AEM.00312-14

Juntanawiwat, P., Thunyaharn, S., Visawapoka, U., Samosornsuk, W., & Samosornsuk, S. (2016). Prevalence of OXA–type carbapenemase genes in carbapenem-resistant Acinetobacter baumannii isolates from patients in intensive care unit at Phramongkutklao Hospital. Journal of Medical Technology and Physical Therapy, 28(2), 120-128. DOI: https://www.tci-thaijo.org/index.php/ams/article/view/67950

Lee, K., Lee, W. G., Uh, Y., Ha, G. Y., Cho, J., & Chong, Y. (2003). VIM- and IMP-type metallo-β-lactamase-producing Pseudomonas spp. and Acinetobacter spp. in Korean Hospitals. Emerging Infectious Diseases, 9(7), 868-871. DOI: https://doi.org/10.3201/eid0907.030012

Lee K., Yum J.H., Yong D., Lee H.M., Kim H.D., Docquier J.-D., Rossolini G.M., Chong Y. (2005) Novel acquired metallo-beta-lactamase gene, blaSIM-1, in a class 1 integron from Acinetobacter baumannii clinical isolates from Korea. Antimicrobial Agents and Chemotherapy, 49(11), 4485-4491. DOI: https://doi.org/10.1128/ AAC.49.11.4485-4491.2005

Leungtongkam, U., Thummeepak, R., Wongprachan, S., Thongsuk, P., Kitti, T., Ketwong, K., Runcharoen, C., Chantratita, N., & Sitthisak, S. (2018). Dissemination of bla OXA-23 , bla OXA-24 , bla OXA-58 , and bla NDM-1 genes of Acinetobacter baumannii isolates from four tertiary hospitals in Thailand. Microbial Drug Resistance, 24(1), 55-62. DOI: https://doi.org/10.1089/mdr.2016.0248

Lob, S. H., Hoban, D. J., Sahm, D. F., & Badal, R. E. (2016). Regional differences and trends in antimicrobial susceptibility of Acinetobacter baumannii. International Journal of Antimicrobial Agents, 47(4), 317-323. DOI: https://doi.org/10.1016/j.ijantimicag.2016.01.015

Magiorakos, A. P., Srinivasan, A., Carey, R. B., Carmeli, Y., Falagas, M. E., Giske, C. G., ... & Monnet, D. L. (2012). Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clinical Microbiology and Infection, 18(3), 268-281. DOI: https://doi.org/10.1111/j.1469-0691.2011.03570.x

National Antimicrobial Resistance Surveillance Thailand (NARST). (2018). The situation of antimicrobial resistance 2000-2018. Retrieved from http://narst.dmsc.moph.go.th/data/AMR%202000-2018-12M.pdf

Nigro, S. J., & Hall, R. M. (2016). Structure and context of Acinetobacter transposons carrying the oxa23 carbapenemase gene. Journal of Antimicrobial Chemotherapy, 71(5), 1135-1147. Doi:

https://doi.org/10.1093/jac/dkv440

Palzkill, T. (2013). Metallo-β-lactamase structure and function: metallo-β-lactamase structure and function. Annals of the New York Academy of Sciences, 1277(1), 91-104. DOI: https://doi.org/10.1111/j.1749-6632.2012.06796.x

Poirel, L., Lebessi, E., Héritier, C., Patsoura, A., Foustoukou, M., & Nordmann, P. (2006). Nosocomial spread of OXA-58-positive carbapenem-resistant Acinetobacter baumannii isolates in a paediatric hospital in Greece. Clinical Microbiology and Infection, 12(11), 1138-1141. DOI: https://doi.org/10.1111/j.1469-0691.2006.01537.x

Poirel, L., & Nordmann, P. (2006). Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clinical Microbiology and Infection, 12(9), 826-836. DOI: https://doi.org/10.1111/j.1469-0691.2006.01456.x

Queenan, A. M., & Bush, K. (2007). Carbapenemases: The versatile β-lactamases. Clinical Microbiology Reviews, 20(3), 440-458. DOI: https://doi.org/10.1128/CMR.00001-07

Thirapanmethee, K., Srisiri-a-nun, T., Houngsaitong, J., Montakantikul, P., Khuntayaporn, P., & Chomnawang, M. (2020). Prevalence of OXA-type β-lactamase genes among carbapenem-resistant Acinetobacter baumannii clinical isolates in Thailand. Antibiotics, 9(12), 864. DOI: https://doi.org/10.3390/antibiotics9120864

Turton, J. F., Woodford, N., Glover, J., Yarde, S., Kaufmann, M. E., & Pitt, T. L. (2006). Identification of Acinetobacter baumannii by detection of the blaOXA-51-like carbapenemase gene intrinsic to this species. Journal of Clinical Microbiology, 44(8), 2974-2976. DOI: https://doi.org/10.1128/JCM.01021-06

Valenzuela, J. K., Thomas, L., Partridge, S. R., van der Reijden, T., Dijkshoorn, L., & Iredell, J. (2007). Horizontal gene transfer in a polyclonal outbreak of carbapenem-resistant Acinetobacter baumannii. Journal of Clinical Microbiology, 45(2), 453-460. DOI: https://doi.org/10.1128/JCM.01971-06

Vashist, J., Tiwari, V., Das, R., Kapil, A., & Rajeswari, M. R. (2011). Analysis of penicillin-binding proteins (PBPs) in carbapenem resistant Acinetobacter baumannii. The Indian Journal of Medical Research, 133(3), 332-338. PMID: 21441690; PMCID: PMC3103161.

Walsh, T. R., Toleman, M. A., Poirel, L., & Nordmann, P. (2005). Metallo-β-lactamases: the quiet before the storm? Clinical Microbiology Reviews, 18(2), 306-325. DOI: https://doi.org/10.1128/CMR.18.2.306-325.2005

Walther-Rasmussen, J., & Høiby, N. (2006). OXA-type carbapenemases. Journal of Antimicrobial Chemotherapy, 57(3), 373-383. DOI: https://doi.org/10.1093/jac/dki482

Wang, T.-H., Leu, Y.-S., Wang, N.-Y., Liu, C.-P., & Yan, T.-R. (2018). Prevalence of different carbapenemase genes among carbapenem-resistant Acinetobacter baumannii blood isolates in Taiwan. Antimicrobial Resistance and Infection Control, 7, 123. DOI: https://doi.org/10.1186/s13756-018-0410-5

Woodford, N., Ellington, M. J., Coelho, J. M., Turton, J. F., Ward, M. E., Brown, S., ... & Livermore, D. M. (2006). Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp. International Journal of Antimicrobial Agents, 27(4), 351-353. DOI: https://doi.org/10.1016/j.ijantimicag.2006.01.004