A comparative evaluation of aztreonam-avibactam and ceftazidime-avibactam plus aztreonam for infections due to MBL-producing Enterobacterales

OBJECTIVES: Aztreonam-avibactam (ATM-AVI) and ceftazidime-avibactam plus aztreonam (CAZ/AVI-ATM) represent therapeutic strategies for infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales. This perspective synthesizes mechanistic rationale, microbiologic determinants of activity, pharmacokinetic/pharmacodynamic principles, and available clinical outcomes to compare these regimens and identify knowledge gaps. METHODS: We critically reviewed mechanistic, microbiological, pharmacokinetic/pharmacodynamic, and clinical evidence relevant to the use of ATM-AVI and CAZ/AVI-ATM against MBL-producing Enterobacterales. RESULTS: Both approaches are expected to provide activity against MBL-producing organisms; however, important distinctions exist. ATM-AVI ensures fixed and predictable co-exposure of aztreonam and avibactam, minimizing the risk of pharmacokinetic asynchrony inherent to administering CAZ/AVI with separate aztreonam. The efficacy of ATM-AVI may nevertheless be influenced by organism-specific resistance mechanisms and pharmacologic variables. CAZ/AVI-ATM offers a pragmatic alternative but introduces logistical complexity and potential variability in inhibitor exposure. Observational data appear more favorable for ATM-AVI, although direct comparisons are not available. CONCLUSION: In the absence of direct comparative trials, regimen selection should consider renal function, infection syndrome, and the feasibility of sustaining adequate inhibitor exposure.