Publication:

In vitro assessment of ceftazidime-avibactam combined with aztreonam for mitigating antimicrobial resistance in clinical isolates of multidrug-resistant Gram-negative bacilli

Background Antimicrobial resistance (AMR) represents a major global public health threat, with increasing MDR infections caused by Gram-negative such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. The limited antibiotic pipeline and ineffective treatments have necessitated the development of novel drug combinations. Among these, the combination of ceftazidime-avibactam with aztreonam has shown promise, particularly against serine-β-lactamase and metallo-β-lactamase producing strains that are resistant to conventional therapeutics.

Methods Identification of isolates was done by routine biochemical testing; AST was determined by Kirby-Bauer disc diffusion, interpreted by CLSI guidelines. MDR, XDR, PDR were characterized. ESBL producers and carbapenem resistant strains were detected phenotypically using CLSI guidelines. In vitro synergy of ceftazidime-avibactam plus aztreonam was assessed by broth disc elution, following CLSI recommendations.

Results Of 183 isolates of gram-negative bacilli, Escherichia coli (n=67), Klebsiella pneumoniae (n=72), Pseudomonas aeruginosa (n=29) and Acinetobacter spp. (n=15) in which MDR 68.65% was reported in Escherichia coli and 66.66% of XDR was reported in Klebsiella pneumoniae. ESBL was detected in 68 of 80 Enterobacterales, while 90 of 150 tested GNB were carbapenem resistant; Klebsiella pneumoniae contributed highest numbers. The combination of ceftazidime-avibactam with aztreonam yielded synergistic activity in 83.4% of all GNB isolates. Within carbapenem-resistant Enterobacterales, susceptibility to the combination was 97.2%, contrasting with only 15.7% susceptibility among carbapenem-resistant non-fermenters. Resistance to the combination was especially high among XDR and PDR Acinetobacter spp. and Pseudomonas aeruginosa.

Conclusions The combination of ceftazidime-avibactam with aztreonam demonstrates strong in vitro synergy and enhanced susceptibility against MDR and carbapenemase-producing Enterobacterales especially Klebsiella pneumoniae suggesting clinical promise where conventional drugs fail. However, limited efficacy was observed against non-fermenter groups, underscoring the need for continuing resistance surveillance and further therapeutic innovation in multidrug-resistant non-fermenters.