OBJECTIVES: Aztreonam-Avibactam (ATM-AVI) is a combination therapy including the monobactam aztreonam (ATM) and the non-β-lactam β-lactamase inhibitor avibactam (AVI). A Phase 3 randomised clinical trial (REVISIT) investigated ATM-AVI for the treatment of serious Gram-negative infections (GNI) including MBL-producing pathogens for which there are limited treatment options (LTO). This analysis evaluates the cost-effectiveness of ATM-AVI ± metronidazole versus meropenem ± colistin for the treatment of complicated intra-abdominal infections (cIAI) and hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) in the Italian setting. Uncertainty in the model was assessed using probabilistic sensitivity analysis, one-way deterministic sensitivity analysis, and scenario analyses.

METHODS: A cost-effectiveness analysis used a decision tree model that simulates the clinical pathway, followed by a Markov model to capture lifetime impacts on cured patients was used. The model adopted Italian National Health System perspective with a 3% discount rate. Treatment response rates were taken from REVISIT, with separate analyses for the cIAI and HAP/VAP populations. The impact of resistant pathogens from recent literature was included as an additional factor

RESULTS: The key drivers of the model are the response rates from REVISIT and the impact of resistant pathogens which influence QALY gains from survival in the long-term model. For cIAI, treatment with ATM-AVI ± metronidazole versus meropenem ± colistin leads to a gain of 0.23 LYs, 0.21 QALYs, and incremental costs of €3,970, generating an ICER of €18,997/QALY. For the HAP/VAP, there was a gain of 0.46 LYs, 0.42 QALYs, and incremental costs of €4,480, generating an ICER of €10,725/QALY. For both cIAI and HAP/VAP indications, the ICER is well below the willingness-to-pay threshold of €30,000/QALY accepted in Italy.

CONCLUSIONS: The introduction of ATM-AVI will lead to improved outcomes for patients with cIAI and HAP/VAP, with a minimal cost impact in the Italian setting, meaning that ATM-AVI is a cost-effective strategy compared to meropenem.