The synergy between ceftazidime/avibactam and aztreonam against metallo-beta-lactamase positive isolates from an oncology center in eastern India

BACKGROUND: Ceftazidime/avibactam plus aztreonam has emerged as an important antimicrobial combination for empirical and targeted therapy of suspected or confirmed metallo-beta-lactamase positive carbapenem resistant Gram-negative bacterial infections (especially in Enterobacterales). As this combination is not necessarily synergistic against target pathogens it is essential that synergy test is done whenever clinically indicated. However, real-world information is scarce with regard to clinical sample and organism specific synergism data. In this study we present data from an oncology hospital in eastern India. METHOD: We performed bacterial identification and phenotypic antibiotic susceptibility using VITEK®-2 Compact system. Carbapenemase resistance genes in bacteria were detected by end-point multiplex PCR. We tested phenotypic synergy of Ceftazidime/avibactam plus aztreonam by broth micro-dilution (of 302 isolates). RESULTS: In blood culture samples Klebsiella pneumoniae showed the maximum synergism (97.43%), followed by Escherichia coli (66.63%) and Pseudomonas aeruginosa (33.33%). Among urine culture samples Klebsiella pneumoniae showed the maximum synergism (96.22%), followed by E. coli (78.04%) and P. aeruginosa only (17.64%). Among respiratory cultures (sputum, endotracheal secretion, broncho-alveolar lavage) Klebsiella pneumoniae showed maximum synergism (91.66%), followed by E. coli (80%) and P. aeruginosa (37.5%). Among isolates from pus and other body fluid samples Klebsiella pneumoniae had maximum synergism (96.87%), followed by E. coli (93.54%) and P. aeruginosa (36.36%). CONCLUSIONS: Inappropriate use and over use of Ceftazidime/avibactam and aztreonam would not only harm antimicrobial stewardship but also result in development of antimicrobial resistance and financial burden. Clinical microbiology laboratories in India need to provide services for Ceftazidime/avibactam with aztreonam synergy testing to facilitate patient management.