Estimating the Value of Aztreonam-Avibactam in Treating Metallo-beta-Lactamase-Producing Enterobacterales Infections in Spain Using the STEDI AMR Value Framework.

Introduction: Treatments for serious infections caused by multidrug-resistant gram-negative bacteria, including metallo-β-lactamase-producing Enterobacterales (MBL-EB), are limited and aztreonam with avibactam (ATM-AVI) is the first β-lactam/β-lactamase inhibitor combination active against MBL-EB approved in Europe and approved for reimbursement by the Spanish National Health System (NHS). This study aims to estimate the value of adding ATM-AVI as a new first-line treatment into the current strategy (ATM-AVI → cefiderocol → colistin + meropenem) in patients with hospital-acquired/ventilator-associated pneumonia (HAP/VAP) and complicated intra-abdominal infections (cIAI), caused by MBL-EB from the Spanish NHS perspective.

Methods: A dynamic disease transmission model was developed to assess the value of ATM-AVI considering the transmission, diversity and enablement components of the value framework for antibiotics, called STEDI (spectrum, transmission, enablement, diversity, insurance). Transmission and diversity value were described by estimating direct population-level impact on treatment outcomes and resistance development. Enablement value was estimated by linking population-level improvements in antimicrobial effectiveness into improved prophylactic effectiveness. Inputs for efficacy, resistance, adverse events, and costs were sourced from the REVISIT study, literature and expert opinion. A 10-year infection transmission horizon was used; quality-adjusted life years (QALYs) were estimated over a lifetime and valued using a willingness-to-pay (WTP) threshold of €25,000/QALY gained to calculate the net monetary benefit (NMB). Costs and benefits were discounted at a rate of 3%.

Results: Over 10 years, the intervention strategy introducing ATM-AVI was dominant, leading to a 2.96% proportional reduction in resistance, 19,533 fewer infections and 4662 lives saved (47,319 QALYs gained) and a cost saving of €40.5 million. The NMB was €1.22 billion.

Conclusions: In Spain, ATM-AVI is a highly cost-effective and urgently needed treatment option for patients with MBL-EB including HAP/VAP and cIAI infections. Using the novel STEDI framework unlocks the considerable value of a new antibiotic which is essential to support incentives for the development of new antimicrobials.