Aztreonam-amoxicillin/clavulanate combination therapy against bla _NDM-producing Enterobacterales infections

Background: Aztreonam plus ceftazidime/avibactam is recommended against NDM-producing Enterobacterales. Pairing with clavulanate can also restore aztreonam’s activity. Objectives: To report on the clinical experience with antimicrobial susceptibility testing–guided aztreonam therapy combined with β-lactamase inhibitors, particularly amoxicillin-clavulanate, against NDM-producing Enterobacterales infections. Methods: All patients with infections caused by NDM-producing Enterobacterales that were resistant to aztreonam monotherapy but demonstrated in vitro synergy and thus eligible for aztreonam combination therapy, who received ≥5 days of aztreonam-based combination therapy, were included. Gradient strip-crossing methodology was validated against broth microdilution for susceptibility testing. Clinical response was assessed at 30 days post-treatment. Results: Clinical cure was achieved in 78% (7/9) of aztreonam/amoxicillin-clavulanate patients and 56% (9/16) of aztreonam/ceftazidime-avibactam patients. Treatment duration averaged 11.8 and 11.6 days, respectively. Among 21 sequenced isolates, bla _NDM-1 was most prevalent. In vitro synergy was demonstrated in 52% with clavulanate and 90% of isolates with avibactam. Gradient strip-crossing showed 80% essential agreement and 100% categorical agreement for both combinations. Transient hepatic enzyme elevations occurred in three liver transplant recipients. Conclusions: Our findings suggest aztreonam/amoxicillin-clavulanate combination therapy guided by gradient strip-crossing as a potential broad-spectrum-sparing strategy for selected patients with NDM-producing Enterobacterales infections.