Follow
International Journal of Current Microbiology and Applied Sciences (IJCMAS)
IJCMAS is now DOI (CrossRef) registered Research Journal. The DOIs are assigned to all published IJCMAS Articles.
Index Copernicus ICI Journals Master List 2023 - IJCMAS--ICV 2023: 95.56 For more details click here
National Academy of Agricultural Sciences (NAAS) : NAAS Score: *5.38 (2020) [Effective from January 1, 2020] For more details click here

Login as a Reviewer


See Guidelines to Authors
Current Issues
Download Publication Certificate

Original Research Articles                      Volume : 14, Issue:6, June, 2025

PRINT ISSN : 2319-7692
Online ISSN : 2319-7706
Issues : 12 per year
Publisher : Excellent Publishers
Email : editorijcmas@gmail.com /
submit@ijcmas.com
Editor-in-chief: Dr.M.Prakash
Index Copernicus ICV 2018: 95.39
NAAS RATING 2020: 5.38

Int.J.Curr.Microbiol.App.Sci.2025.14(6): 101-108
DOI: https://doi.org/10.20546/ijcmas.2025.1406.009


In-vitro Evaluation of Synergy Testing of Ceftazidime-Avibactam-Aztreonam among Carbapenem-Resistant Gram-Negative Organisms
Department of Microbiology, Pondicherry Institute of Medical Sciences, India
*Corresponding author
Abstract:

The prevalence of severe infections due to Carbapenemase –resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CR-PA) has increased worldwide. The treatment has become challenging and limited among the metallo-β-lactamases (MBLs) producing organisms due to the rise in polymyxin resistance. Due to the paucity of novel drugs, the ceftazidime-avibactam-aztreonam serves as a wonder drug combination for these infections. In 2024, Clinical and Laboratory Standards Institute (CLSI) approved broth disk elution method for synergy testing. This study was performed to evaluate the ceftazidime-avibactam-aztreonam synergy testing against the MBL-producing clinical isolates. We used a total of 34 archived multidrug-resistant organisms (MDROs) from the Microbiology department over a six-month period, from July to December 2023. All these isolates were subjected to modified carbapenem inactivation method (m CIM) and EDTA carbapenem inactivation method (e CIM) for phenotypic detection of carbapenemases. The ceftazidime-avibactam-aztreonam synergy testing was performed by two methods: Disk diffusion method and disk elution method among MBL-producing isolates. The study revealed that among the 34 MDR clinical isolates, 21 (62%) were MBL producers, followed by 5 (15%) Serine beta lactamase producers, 3 (9%) Indeterminate and 5(15%) were negative. MBL producers were subjected to two methods of synergy testing. Among 21 MBL-producing isolates, synergy was observed in 13 (38.2%) and no synergy was seen in eight (24%) isolates by both methods. There were no discrepant results. Detection of synergism for ceftazidime-avibactam-aztreonam combination can be determined by the disk diffusion method in a low-resource setting and thereby aid in clinical decision-making.


Keywords: Ceftazidime-avibactam-aztreonam, Synergy testing, Broth disk elution method


References:

Aqel, A.A., Giakkoupi, P., Alzoubi, H., Masalha, I., Ellington, M.J. and Vatopoulos, A., 2017. Detection of OXA-48-like and NDM carbapenemases producing Klebsiella pneumoniae in Jordan: A pilot study. Journal of Infection and Public Health, 10(2), pp.150-155. https://doi.org/10.1016/j.jiph.2016.02.002  

Benchetrit, L., Mathy, V., Armand-Lefevre, L., Bouadma, L. and Timsit, J.F., 2020. Successful treatment of septic shock due to NDM-1-producing Klebsiella pneumoniae using ceftazidime/avibactam combined with aztreonam in solid organ transplant recipients: report of two cases. International Journal of Antimicrobial Agents, 55(1), p.105842.https://doi.org/10.1016/j.ijantimicag.2019.10.023

CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 34th ed. CLSI supplement M100. Clinical and Laboratory Standards Institute; 2024.

Deepashree Rajshekar, Sujatha S R , Krishna Karthik M V S, Sreejith Raveendran. 2024 Evaluation of phenotypic carbapenem inactivation methods among carbapenem resistant gram-negative bacteria isolated from blood culture specimens and their synergy testing. Indian Journal of Microbiology Research. 11(3): 175-179. https://doi.org/10.18231/j.ijmr.2024.032

Filgona, J., Banerjee, T. and Anupurba, S., 2018. Endemicity of OXA-48 and NDM-1 Carbapenemase producing Klebsiella pneumoniae and Escherichia coli from a tertiary hospital in Varanasi, India. JAMB, 12, pp.1-8. DOI: 10.9734/JAMB/2018/43928

Harris, H., Tao, L., Jacobs, E.B., Bergman, Y., Adebayo, A., Tekle, T., Lewis, S., Dahlquist, A., Abbey, T.C., Wenzler, E. and Humphries, R., 2023. Multicenter evaluation of an MIC-based aztreonam and ceftazidime-avibactam broth disk elution test. Journal of clinical microbiology, 61(5), pp.e01647-22. https://doi.org/10.1128/jcm.01647-22

Kalaivani, R., Kali, A., Surendran, R., Sujaritha, T. and Babu, C.G., 2024. Rapid characterization of carbapenem-resistant Enterobacterales by multiplex lateral flow assay and detection of ceftazidime-avibactam-aztreonam synergy. Indian Journal of Medical Microbiology, 47, p.100530. https://doi.org/10.1016/j.ijmmb.2024.100530

Khan, A., Erickson, S.G., Pettaway, C., Arias, C.A., Miller, W.R. and Bhatti, M.M., 2021. Evaluation of susceptibility testing methods for aztreonam and ceftazidime-avibactam combination therapy on extensively drug-resistant gram-negative organisms. Antimicrobial agents and chemotherapy, 65(11), pp.10-1128. https://doi.org/10.1128/AAC.00846-21

Marshall, S., Hujer, A.M., Rojas, L.J., Papp-Wallace, K.M., Humphries, R.M., Spellberg, B., Hujer, K.M., Marshall, E.K., Rudin, S.D., Perez, F. and Wilson, B.M., 2017. Can ceftazidime-avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae?. Antimicrobial agents and chemotherapy, 61(4), pp.10-1128. https://doi.org/10.1128/AAC.02243-16

Rajshekar D, Sujatha S R, Krishna Karthik M V S, Raveendran S, Evaluation of phenotypic carbapenem inactivation methods among carbapenem resistant gram-negative bacteria isolated from blood culture specimens and their synergy testing. Indian J Microbiol Res 2024;11(3):175-179. https://doi.org/10.18231/j.ijmr.2024.032

Reddy, R.M., Kumar, S. and Kumar, M., 2017. Characterization of VIM and IMP Metallo-β-lactamases (MBL) in Pseudomonas aeruginosa isolated in a tertiary care hospital. Int J Curr Microbiol Appl Sci, 6(3), pp.1461-1467. DOI: 10.3947/ic.2015.47.2.81

Sreenivasan, P., Sharma, B., Kaur, S., Rana, S., Biswal, M., Ray, P. and Angrup, A., 2022. In-vitro susceptibility testing methods for the combination of ceftazidime-avibactam with aztreonam in metallobeta-lactamase producing organisms: Role of combination drugs in antibiotic resistance era. The Journal of Antibiotics, 75(8), pp.454-462. https://doi.org/10.1038/s41429-022-00537-3

Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D.L., Pulcini, C., Kahlmeter, G., Kluytmans, J., Carmeli, Y. and Ouellette, M., 2018. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet infectious diseases, 18(3), pp.318-327. https://doi.org/10.1016/S1473-3099(17)30753-3  


Download this article as Download

How to cite this article:

Sridevi Dinakaran, Sheela Devi Chandrakesan and Sandhya Bhat, K. 2025. In-vitro Evaluation of Synergy Testing of Ceftazidime-Avibactam-Aztreonam among Carbapenem-Resistant Gram-Negative Organisms.Int.J.Curr.Microbiol.App.Sci. 14(6): 101-108. doi: https://doi.org/10.20546/ijcmas.2025.1406.009
Copyright: This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license.

Citations