In Vitro Susceptibility Comparison of Aztreonam Along With Ceftazidime-Avibactam Synergy Testing Methods and Aztreonamavibactam Against Carbapenem Resistant Organisms in Isolates Obtained From Cancer Patients

Introduction: The global rise of multidrug-resistant (MDR) Gram-negative pathogens, particularly carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa, presents a critical therapeutic challenge. Resistance is often driven by the co-expression of metallo-βlactamases (MBLs) like NDM, along with serine β-lactamases (e.g., ESBLs, AmpC). Aztreonam (ATM) retains intrinsic activity against MBLs but is hydrolyzed by serine β-lactamases. Avibactam, a novel non-β-lactam β-lactamase inhibitor, inhibits class A, C, and some class D enzymes but lacks efficacy against MBLs. The combination of drugs like aztreonam and avibactam (ATM-AVI) offers a promising strategy to overcome such dual resistance. Objective: To evaluate the in vitro efficacy of the aztreonam-avibactam combination against carbapenem-resistant, NDMproducing Gram-negative bacilli and to compare it with Ceftazidime-Avibactam along with Aztreonam. Method: A total of 100 non-duplicate clinical isolates of Carbapenem Resistant Organisms (CRO) were recovered from cancer patients in a tertiary care hospital. Resistant genotype was confirmed and those isolates showing NDM genotype with or without other resistant genotypes were included in the study. Synergy between Aztreonam and Ceftazidime-avibactam was assessed using three techniques: ICMR recommended strip and disc method, Broth Disc Elution (BDE) method with 5ml of broth (CLSI recommended) and 7.5ml broth (Inhouse modified) method. The isolates were also tested by AztreonamAvibactam E-strips. Results: Of the 100 isolates, susceptibility of ATM-AVI was observed in 79% isolates. Isolates were most susceptible to Ceftazidime Avibactam along with Aztreonam by broth disc elution method (CLSI-75% and inhouse modification-79%). Conclusion: The use of broth disk elution method proved to be practical and reliable approaches for synergy testing in routine clinical microbiology laboratories. Aztreonam-avibactam (ATM-AVI) exhibits robust in vitro activity against NDM-producing Gram-negative bacilli, representing a promising therapeutic option in the context of increasing metallo-β-lactamase (MBL) prevalence. These findings underscore the potential clinical utility of ATM-AVI in managing infections caused by multidrug-resistant, NDM-producing pathogens, particularly in high-burden settings.