aztreonam + ceftazidime + avibactam + colistin

This is a combination of four antibiotics—aztreonam, ceftazidime, avibactam, and colistin—used together as a salvage or last-resort therapy for severe infections caused by multidrug-resistant Gram-negative bacteria, particularly those producing metallo-β-lactamases (MBLs) such as certain strains of Klebsiella pneumoniae.

• Aztreonam is a monobactam antibiotic that is stable against hydrolysis by MBLs but can be inactivated by other β-lactamases.
• Ceftazidime is a third-generation cephalosporin with activity against many Gram-negative organisms.
• Avibactam is a non-β-lactam β-lactamase inhibitor that inhibits class A and C β-lactamases but not MBLs; it restores the activity of partner antibiotics like ceftazidime and protects aztreonam from degradation by co-produced serine β-lactamases when used in combination.
• Colistin (polymyxin E) disrupts bacterial cell membranes and serves as an additional agent active against highly resistant strains.

This quadruple regimen has been reported in case studies for treating life-threatening infections where standard therapies have failed due to resistance. The rationale for combining these agents lies in their complementary mechanisms to overcome multiple resistance pathways present in carbapenemase-producing Enterobacteriaceae, especially those expressing both MBLs and other β-lactamases. Colistin adds further coverage through its distinct mechanism.