aztreonam + ceftazidime-avibactam + fosfomycin

This is a combination antimicrobial regimen consisting of three agents:

• Aztreonam is a monobactam β-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding protein 3 (PBP3), primarily active against Gram-negative bacteria and notable for its stability against metallo-β-lactamases (MBLs).
• Ceftazidime-avibactam combines ceftazidime, a third-generation cephalosporin that inhibits cell wall synthesis via PBP binding, with avibactam, a non-β-lactam β-lactamase inhibitor effective against class A, C, and some D β-lactamases. This combination restores activity of ceftazidime against many resistant organisms.
• Fosfomycin is an epoxide antibiotic that inhibits the initial step in bacterial cell wall synthesis by targeting MurA enzyme.

The rationale for combining these drugs is to provide broad-spectrum coverage—including activity against multidrug-resistant (MDR) Gram-negative pathogens such as Pseudomonas aeruginosa and MBL-producing Enterobacterales. Aztreonam resists hydrolysis by MBLs but can be inactivated by other β-lactamases; avibactam protects both aztreonam and ceftazidime from these enzymes. Fosfomycin adds further synergy through its distinct mechanism. Preclinical studies demonstrate this triple combination can suppress resistance emergence and achieve superior bactericidal effects compared to monotherapy or dual combinations.