Introduction: Infections caused by multidrug-resistant Enterobacterales pose a significant global health challenge, thus necessitating novel therapeutic strategies. The increasing prevalence of carbapenem-resistant Enterobacterales has led to reliance on colistin and polymyxins as last-resort antibiotics. However, emerging colistin resistance and associated polymyxin toxicity have significantly limited their use.
Aztreonam is effective against metallo-β-lactamase (MBL)-producing pathogens but requires protection from co-produced enzymes such as extended-spectrum β-lactamases (ESBLs), AmpC cephalosporinases, and other carbapenemases. Avibactam, a non-β-lactam β-lactamase inhibitor, inhibits ESBLs, Klebsiella pneumoniae carbapenemase (KPC), certain oxacillinase (OXA)-۴۸-like enzymes, and AmpC cephalosporinases but is ineffective against metallo-β-lactamases. This study evaluated the in vitro synergy of ceftazidime-avibactam with aztreonam as a potential colistin-sparing strategy for carbapenem-resistant Enterobacterales infections. Methods: In a prospective cross-sectional study from July ۲۰۲۲ to June ۲۰۲۳, ۹۷ carbapenem-resistant Gram-negative clinical isolates (prevalence: ۹۷/۸۸۷۶ =۱.۰۹%) were obtained from ۸۸۷۶ samples tested for aerobic bacterial culture and antimicrobial susceptibility at a tertiary care hospital in Pune, India. For ۶۹ Enterobacterales isolates resistant to ertapenem, imipenem, and meropenem, synergy between ceftazidime-avibactam and aztreonam was tested using disk diffusion and modified E-test/disk diffusion method, interpreted as per the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Results: Enterobacterales comprised ۶۹ (۷۱.۱۳%) of isolates, with ۳۵ (۵۰.۷۳%) of these demonstrating synergy between ceftazidime-avibactam and aztreonam. Klebsiella pneumoniae (۳۳/۶۹; ۴۷.۸۳%) was the predominant species, followed by Escherichia coli (۲۶/۶۹; ۳۷.۶۸%) and Citrobacter species (۱۰/۶۹; ۱۴.۴۹%). Conclusion: In vitro synergy between ceftazidime-avibactam and aztreonam was observed in ۵۰.۷۳% of carbapenem-resistant Enterobacterales isolates, suggesting a possible colistin-sparing alternative for infections such as complicated urinary tract infections, intra-abdominal infections, and hospital-acquired pneumonia; however, further clinical studies are needed to validate its efficacy.
