Assessing The In Vitro Activity Of Ceftazidime - Avibactam And Aztreonam Among Carbapenemase Producing Enterobacterales: Defining The Zone Of Hope By Disc Diffusion Method

Abstract

Background: Antimicrobial resistance is one among the top global public health and development threats creating a great challenge in therapy. Infections caused by carbapenem resistant Enterobacterales (CRE) are extremely difficult to treat and are associated with high mortality. The Indian Council of Medical Research has reported an increasing carbapenem resistance among Enterobacterales. The clinical use of Polymyxin and Tigecycline are limited and can be avoided with the availability of beta-lactam and beta-lactamase inhibitor - Ceftazidime-avibactam (CAZ-AVI) approved in India. But this combination is found to have no activity against metallo-beta-lactamases. Therefore, combining Ceftazidime-avibactam (CAZ-AVI) and Aztreonam (ATM) for these resistant organisms becomes essential. Methods: A total of 137 carbapenem resistant enterobacterales isolates were included in the study. Phenotypic detection of carbapenemases (MBL- metallo beta lactemases and serine carbapenemase) was identified using modified carbapenem inactivation method (mCIM) and EDTA- carbapenem inactivation method (eCIM). The synergy between in vitro activity of Ceftazidime-avibactam and Aztreonam among Carbapenemase producing Enterobacterales is identified by Disc diffusion method.
Results: Among the 1220 enterobacterales species, 137 (11.23%) isolates were resistant to carbapenems. Out of 137 isolates 76 isolates were metallo betalactamase (MBL) producers and 61 isolates were serine carbapenemase producers. The 76 MBL producing isolates were processed further for the Ceftazidime avibactum and Aztreonam synergy. Out of the total MBL isolates the drug synergy was identified in 68 (89.47%) isolates.
Conclusion: This simple in vitro antimicrobial susceptibility testing of Ceftazidime-avibactam with Aztreonam, gives us a hope on this combination therapy for potential MBL-CRE infections in the developing countries like India, where MBL producing infections predominate. Phenotypic detection of carbapenemases may be used as reliable alternative to traditional molecular diagnostic methods.