Antibiotics · Published 2026-07-29 · DOI 10.3390/antibiotics15080733
James A. Karlowsky, Mark G. Wise, Qifeng Shi, Wenming Zhang, Meijie Le, Jianguo Li
<b>Objectives</b>: The intent of this study was to report reference in vitro antimicrobial susceptibility testing results for funobactam (formerly XNW4107) in combination with imipenem against recent, worldwide clinical isolates of Gram-negative bacilli. <b>Methods</b>: MICs for imipenem in combination with a fixed concentration of funobactam (8 mg/L), and seven comparator agents, were determined using the reference CLSI M07 broth microdilution method for 4003 clinical isolates of Gram-negative bacilli (2008 Enterobacterales, 999 <i>Acinetobacter baumannii</i>, and 996 <i>Pseudomonas aeruginosa</i>) collected from 211 unique clinical laboratory sites in 54 countries as part of industry-sponsored antimicrobial surveillance studies in 2021 and 2022. MICs were interpreted by 2026 CLSI M100 breakpoints. Most isolates with imipenem-funobactam MICs of ≥4 mg/L (95.4%) underwent whole genome sequencing to identify acquired β-lactamase gene carriage. <b>Results</b>: MIC<sub>90</sub> values for imipenem-funobactam were 2 mg/L for all 2008 isolates of Enterobacterales, and 1, 0.5, and 0.5 mg/L, respectively, for metallo-β-lactamase (MBL)-negative Enterobacterales (<i>n</i> = 1969), non-<i>Morganellaceae</i> Enterobacterales (NME) (<i>n</i> = 1752), and MBL-negative NME (<i>n</i> = 1718) isolate subsets. MIC<sub>90</sub> values for imipenem-funobactam and imipenem alone were identical or within one doubling dilution for all 14 species of Enterobacterales tested except <i>Klebsiella pneumoniae</i>, <i>Citrobacter freundii</i>, and <i>Enterobacter bugandensis</i> which showed differences of 32-fold (imipenem-funobactam MIC<sub>90</sub>, 0.5 mg/L; imipenem MIC<sub>90</sub>, 16 mg/L), 8-fold (0.25 mg/L; 2 mg/L), and 4-fold (0.25 mg/L; 1 mg/L), respectively. Both for all <i>A. baumannii</i> isolates (<i>n</i> = 999) and for MBL-negative isolates (<i>n</i> = 962), the imipenem-funobactam MIC<sub>90</sub> value (4 mg/L) was 32-fold lower than for imipenem alone (128 mg/L). Both for all <i>P. aeruginosa</i> (<i>n</i> = 996) isolates and MBL-negative isolates (<i>n</i> = 962), we observed a 4-fold difference in potency between imipenem-funobactam (MIC<sub>90</sub>, 4 mg/L) and imipenem alone (MIC<sub>90</sub>, 16 mg/L). Isolates carrying MBL demonstrated the highest MICs for imipenem-funobactam. <b>Conclusions</b>: Imipenem-funobactam demonstrated potent in vitro activity against most carbapenem-resistant isolates of <i>A. baumannii</i>, <i>K. pneumoniae</i>, NME and many isolates of carbapenem-resistant <i>P. aeruginosa</i>. Continued development of imipenem-funobactam is warranted.
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Karlowsky, J., Wise, M., Shi, Q., et al. (2026). In Vitro Activity of Imipenem-Funobactam Against Clinical Isolates of Gram-Negative Bacilli. Antibiotics. https://doi.org/10.3390/antibiotics15080733