Use of Aztreonam–Avibactam with Rapid Eravacycline Step-Down Therapy for a Tibial Septic Non-Union by NDM-Producing Enterobacter cloacae

New Delhi metallo-β-lactamase (NDM)-producing <i>Enterobacterales</i> represent a major therapeutic challenge due to their resistance to nearly all β-lactams and frequent co-resistance to other antibiotic classes, leaving clinicians with few effective options. These challenges are amplified in orthopedic infections with hardware involvement, where biofilm formation and the need for prolonged antimicrobial therapy limit success. We describe a 55-year-old female with a history of right type 3 open pilon fracture complicated by hardware failure and revision, who presented with septic tibial nonunion and chronic drainage. During this admission, she underwent irrigation and debridement with hardware removal and intramedullary nail placement. Cultures grew <i>Enterobacter cloacae</i> complex resistant to meropenem, ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol, as well as <i>Candida parapsilosis</i>. Molecular testing confirmed NDM production, while reference testing showed susceptibility to aztreonam-avibactam (ATM-AVI). The patient was treated with ATM-AVI plus micafungin, achieving clinical stability within three days. Due to outpatient administration barriers with ATM-AVI, the patient was transitioned to eravacycline and micafungin. At eight-week follow-up, the patient remained clinically improved without relapse or adverse effects. This case highlights ATM-AVI as a critical therapy for NDM-producing orthopedic infections involving hardware and supports eravacycline as a feasible step-down option in outpatient management.