Can aztreonam/avibactam combined with fosfomycin be a treatment option for infections caused by NDM-producing Pseudomonas aeruginosa?

In India, most carbapenem-resistant Pseudomonas aeruginosa strains produce metallo-β lactamases, and cefiderocol, the sole reliable treatment option, is currently not available. This study evaluated aztreonam/avibactam with fosfomycin as an alternative in 85 MBL-producing isolates. Aztreonam/avibactam and fosfomycin inhibited 7.1% and 27.1% of isolates at 8 and 32 mg/L, respectively, while cefiderocol at 4 mg/L inhibited 78.8%. Time-kill assays on 10 isolates showed synergy in 7/10 and enhanced activity in 6/10 with the combination versus monotherapy. These findings warrant further in vitro and in vivo pharmacokinetic/pharmacodynamic studies to evaluate the therapeutic potential of aztreonam/avibactam plus fosfomycin against MBL-producing P. aeruginosa. • In India, MBL-producing P. aeruginosa are widely prevalent • Safe treatment options for MBL-Pseudomonas infections are extremely limited • Aztreonam/avibactam or fosfomycin alone were not cidal • For majority of isolates, aztreonam/avibactam and fosfomycin combination were cidal