Analysis of a simple disk diffusion method to evaluate ceftazidime–avibactam/aztreonam combination synergism against New Delhi metallo-beta-lactamase-producing clinical isolates

The rise of multidrug-resistant <i>Enterobacterales</i> and <i>Pseudomonas aeruginosa</i> has diminished the reliability of conventional antibiotics for treating Multidrug Resistant (MDR) infections. The combination of ceftazidime-avibactam with aztreonam has demonstrated <i>in vitro</i> synergism against multidrug-resistant organisms, notably metallo-beta-lactamase-producing strains. Treatment with the ceftazidime-avibactam/aztreonam combination may provide clinical benefits for patients with multidrug-resistant bacterial infections. The present study aimed to detect genes encoding carbapenem resistance in clinical strains and to determine the efficacy of ceftazidime-avibactam/aztreonam against carbapenemase co-producers. A cross-sectional research study was conducted on 62 carbapenem-resistant clinical isolates collected from November 2022 to February 2024. Ceftazidime-avibactam/aztreonam synergy against 55 carbapenemase producers [New Delhi metallo-beta-lactamase (NDM), imipenem-hydrolysing metallo-beta-lactamase (IMP), Verona Integron-encoded metallo-beta-lactamase (VIM) and oxacillinase-48 (OXA-48)] was determined using the disc diffusion method. Data analysis was performed by chi-square test. Ceftazidime-avibactam/aztreonam synergy was identified against 25 (64.1%) out of 39 isolates exhibiting the NDM gene, seven (77.8%) out of nine isolates that were co-producers of NDM and OXA-48 genes, two (50%) out of four isolates co-producing NDM and VIM carbapenemase genes and a single isolate (33.3%) out of three isolates with NDM, VIM and OXA-48 genes. A wide zone of 3-23 mm diameter was observed for <i>Enterobacterales</i> and 6-7 mm for <i>P. aeruginosa</i> with ceftazidime-avibactam/aztreonam in relative to ceftazidime-avibactam and aztreonam discs when tested alone. More than 30% of isolates showed a statistically significant difference in zone diameter for the ceftazidime-avibactam/aztreonam combination (<i>P</i><0.05), when compared with the zone size for ceftazidime-avibactam and aztreonam discs when tested alone. The present study showed the <i>in vitro</i> effectiveness of the ceftazidime-avibactam/aztreonam combination against 63.6% of carbapenem-resistant isolates studied. The disc diffusion method requires less technical expertise, and the test result aids in identifying true clinical synergy by observing the widening of the zone diameter that exceeds the aztreonam susceptibility breakpoint.