ceftazidime + avibactam + colistin

This is a combination of three antibiotics—ceftazidime, avibactam, and colistin—used primarily for the treatment of infections caused by carbapenem-resistant Gram-negative bacilli (CR-GNB), including multidrug-resistant Enterobacteriaceae and Pseudomonas species.

• Ceftazidime is a third-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to penicillin-binding protein 3 (PBP3) in Gram-negative bacteria.
• Avibactam is a non–β-lactam β-lactamase inhibitor that restores the activity of ceftazidime against organisms producing Ambler class A, C, and some D β-lactamases (including KPC and OXA-48 carbapenemases), but not metallo-β-lactamases.
• Colistin is a polymyxin antibiotic that disrupts the bacterial outer membrane by interacting with lipopolysaccharides and phospholipids. It is often reserved for multidrug-resistant Gram-negative infections due to its nephrotoxicity risk.

The rationale for combining these agents lies in their complementary mechanisms of action against highly resistant pathogens. While ceftazidime-avibactam targets most serine β-lactamase producers, adding colistin may broaden coverage or provide synergy against certain resistant strains. However, clinical evidence suggests only partial synergism or additivity between ceftazidime-avibactam and colistin; some studies report no significant improvement in antimicrobial activity when combined compared to monotherapy.

This combination has been used off-label or as salvage therapy in severe CR-GNB infections where few alternatives exist. More research is needed to establish efficacy and safety profiles.