Real-world in vitro activity of newer antibiotics against Enterobacterales and Pseudomonas aeruginosa, including carbapenem-non-susceptible and multidrug-resistant isolates: a multicenter analysis

New antibiotics have been developed to combat antibiotic-resistant Gram-negative pathogens, which are difficult to treat and associated with poor clinical outcomes. We conducted a multicenter evaluation of real-world testing practices and susceptibility to newer antibiotics. Our study included 71 facilities in the BD Insights Research Database (2018-2022) and involved adult patients with a positive culture for Enterobacterales or Pseudomonas aeruginosa and facility-reported antibiotic susceptibility data for cefiderocol (FDC), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), eravacycline (ERV), imipenem-relabactam (I-R), or meropenem-vaborbactam (MVB). A total of 27,531 susceptibility results were available, including 22,111 (80.3%) Enterobacterales and 5,420 (19.7%) P. aeruginosa. Escherichia coli (11,882 [43.2%]) was the most frequently tested potential pathogen, and CZA (13,567 [49.3%]) and C/T (13,299 [48.3%]) had the greatest numbers of susceptibility results. For the other four antibiotics, susceptibility data were available for fewer than 2% of isolates. Susceptibility comparisons should be considered with caution. Among isolates tested, CZA had the highest susceptibility rates for total Enterobacterales (98.7%) and multidrug-resistant (92.9%) and carbapenem-non-susceptible (85.0%) isolates. For P. aeruginosa, FDC had the highest susceptibility rates for total (95.6%) and carbapenem-non-susceptible (93.3%) isolates. The susceptibility of carbapenem-non-susceptible Enterobacterales to CZA and C/T decreased modestly from 2020 to 2022, but carbapenem-non-susceptible P. aeruginosa susceptibility rates increased. We conclude that Gram-negative pathogens have high real-world susceptibility rates to newer antibiotics but may show important differences across resistance profiles. Newer antibiotics are a valuable option for the management of resistant Enterobacterales and P. aeruginosa. Additional effort may be required to integrate these agents into routine clinical care.