Identification of carbapenemase genes and evaluation of in vitro activity of ceftazidime-avibactam against carbapenem-resistant Enterobacterales
DOI:
https://doi.org/10.61529/idjp.v33i4.327Abstract
Background: Infections caused by carbapenem-resistant Enterobacterales are becoming an intensifying global concern because of the scarce treatment options available. Carbapenem resistance plays a major role in increasing morbidity and mortality rates in healthcare settings. Ceftazidime-avibactam (CZA), demonstrates in vitro effectiveness against multi-drug resistant (MDR) organisms. The aim of the study was to identify various types of carbapenemase genes present among carbapenem-resistant Enterobacterales (CRE) and assess the in-vitro activity of ceftazidime-avibactam against carbapenem-resistant Enterobacterales.
Material and Methods: This prospective study was carried out in the Microbiology section of the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from January to May 2024. Carbapenem-resistant Enterobacterales (CRE) isolated from blood cultures of patients were included in the study. The detection of carbapenem-resistant genes was conducted using the Xpert Carba-R assay. Antimicrobial susceptibility testing was performed using the Sensititre automated system.
Results: During this period, sixty CRE isolates, recovered from blood culture samples were analysed. The most prevalent gene detected was NDM, found in 43 isolates (71.66%), followed by a combination of NDM and OXA-48 in 13 isolates (21.66%), and OXA-48 alone in 4 isolates (6.66%). Ceftazidime-avibactam (CZA) exhibited susceptibility in only 4 isolates (6.66%). All four of these isolates carried the OXA-48 gene alone.
Conclusion: The study's findings indicated that, within the timeframe investigated, the NDM gene was the predominant resistant gene among CRE isolates, accounting for 93.33% of cases. Ceftazidime-avibactam demonstrated good activity against CRE isolates carrying the OXA-48 gene alone. However, it was not active against CRE isolates containing the NDM gene.
Key Words: Carbapenem-resistant Enterobacterales, Carbapenemases, Ceftazidime-avibactam
References
Tompkins K, D. van Duin. Treatment for carbapenem-resistant Enterobacterales infections: Recent advances and future directions. Eur J Clin Microbiol Infect Dis. 2021. 40(10): 2053-68. DOI: https://doi.org/10.1007/s10096-021-04296-1
Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States, 2019. 2019. Available at: https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf.
Queenan AM, Bush K. Carbapenemases: The versatile beta-lactamases. Clin Microbiol Rev. 2007; 20(3): 440-58. DOI: https://doi.org/10.1128/cmr.00001-07
Ma J, Song X, Li M, Yu Z, Cheng W, Yu Z, et al. Global spread of carbapenem-resistant Enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy. Microbiol Res, 2023. 266: 127249. DOI: https://doi.org/10.1016/j.micres.2022.127249
Kai, J. and S. Wang, Recent progress on elucidating the molecular mechanism of plasmid-mediated colistin resistance and drug design. Int Microbiol, 2020; 23(3): 355-66. DOI: https://doi.org/10.1007/s10123-019-00112-1
Band VI, Satola SW, Smith RD, Hufnagel DA, Bower C, Conley AB, et al. Colistin heteroresistance is largely undetected among carbapenem-resistant Enterobacterales in the United States. mBio, 2021. 12(1). e02881-20.
DOI: https://doi.org/10.1128/mbio.02881-20
Bassetti M, Righi E, Carnelutti A, Graziano E, Russo A. Multidrug-resistant Klebsiella pneumoniae: Challenges for treatment, prevention and infection control. Expert Rev Anti Infect Ther. 2018: 16 (10): 749-61. DOI: https://doi.org/10.1080/14787210.2018.1522249
Silver LL. Fosfomycin: Mechanism and resistance. Cold Spring Harb Perspect Med. 2017; 7(2): a025262.
DOI: https://doi.org/10.1101/cshperspect.a025262
Sheu CC, Chang YT, Lin SY, Chen YH, Hsueh PR. Infections caused by carbapenem-resistant Enterobacteriaceae: An update on therapeutic options. Front Microbiol. 2019. 10: 80. DOI: https://doi.org/10.3389/fmicb.2019.00080
Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis. 2022; 75(2): 187-212. DOI: https://doi.org/10.1093/cid/ciac268
Sader HS, Castanheira M, Shortridge D, Mendes RE, Flamm RK. Antimicrobial activity of ceftazidime-avibactam tested against multidrug-resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S Medical Centers, 2013 to 2016. Antimicrob Agents Chemother. 2017; 61(11): e01045-17. DOI: https://doi.org/10.1128/aac.01045-17
CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 34th ed. CLSI supplement M100. Clinical and Laboratory Standards Institute; 2024.
Ajulo S, Awosile B. Global antimicrobial resistance and use surveillance system (GLASS 2022): Investigating the relationship between antimicrobial resistance and antimicrobial consumption data across the participating countries. PLoS One, 2024. 19(2): p. e0297921. DOI: https://doi.org/10.1371/journal.pone.0297921
Tacconelli, E., et al., Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018. 18(3): 318-27. DOI: https://doi.org/10.1016/s1473-3099(17)30753-3
Paveenkittiporn W, Kamjumphol W, Ungcharoen R, Kerdsin A. Whole-genome sequencing of clinically isolated carbapenem-resistant Enterobacterales Harboring mcr Genes in Thailand, 2016-2019. Front Microbiol. 2020; 11: 586368. DOI: https://doi.org/10.3389/fmicb.2020.586368
Takeuchi, D., et al., Nationwide surveillance in Thailand revealed genotype-dependent dissemination of carbapenem-resistant Enterobacterales. Microb Genom. 2022. 8(4): 000797. DOI: https://doi.org/10.1099/mgen.0.000797
Garg A, Garg J, Kumar S, Bhattacharya A, Agarwal S, Upadhyay GC. Molecular epidemiology & therapeutic options of carbapenem-resistant Gram-negative bacteria. Indian J Med Res. 2019. 149(2): 285-9. DOI: https://doi.org/10.4103/ijmr.ijmr_36_18
Shirley M. Ceftazidime-Avibactam: A Review in the treatment of serious gram-negative bacterial infections. Drugs. 2018; 78(6): 675-92. DOI: https://doi.org/10.1007/s40265-018-0902-x
Abboud MI, Damblon C, Brem J, Smargiasso N, Mercuri P, Gilbert B, et al. Interaction of avibactam with class B metallo-β-lactamases. Antimicrob Agents Chemother. 2016; 60(10): 5655-62. DOI: https://doi.org/10.1128/aac.00897-16
Ozyurt OK, Tufanoglu P, Cetinkaya O, Ozhak B, Yazisiz H, Ongut G, et al. In vitro activity of cefiderocol and ceftazidime-avibactam, against carbapenemase-producing Enterobacterales. Clin Lab. 2023: 69(1). DOI: https://doi.org/10.7754/clin.lab.2022.220827
Piérard D, Stone GG. In vitro antimicrobial susceptibility of clinical respiratory isolates to ceftazidime-avibactam and comparators (2016-2018). BMC Infect Dis. 2021. 21(1): 600. DOI: https://doi.org/10.1186/s12879-021-06153-0
Kazmierczak KM, Bradford PA, Stone GG, de Jonge BLM, Sahm DF. In Vitro Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam against OXA-48-Carrying Enterobacteriaceae Isolated as Part of the International Network for Optimal Resistance Monitoring (INFORM) Global Surveillance Program from 2012 to 2015. Antimicrob Agents Chemother. 2018; 62(12): e00592-18. DOI: https://doi.org/10.1128/aac.00592-18
Hoşbul T, Aydoğan CN, Kaya S, Bedir O, Gümral R, Albay A, et al. [In Vitro Activity of Ceftazidime-avibactam and Colistin Against Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates]. Mikrobiyol Bul. 2022. 56(2): 218-29.
DOI: https://doi.org/10.5578/mb.20229803
La Bella, G., et al., In vitro activity of ceftazidime/avibactam against carbapenem-nonsusceptible Klebsiella penumoniae isolates collected during the first wave of the SARS-CoV-2 pandemic: a Southern Italy, multicenter, surveillance study. J Global Antimicrob Resist. 2022. 31: 236-38. DOI: https://doi.org/10.1016/j.jgar.2022.09.013
Pontikis K, Karaiskos I, Bastani S, Dimopoulos G, Kalogirou M, Katsiari M, et al. Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria. Int J Antimicrob Agents, 2014. 43(1): 52-9.
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