Cost-Effectiveness Analysis of Aztreonam-Avibactam (ATM-AVI) Versus Colistin + Meropenem (COL + MER) for the Treatment of Infections Caused by Metallo-β-Lactamase (MBL)-Producing Enterobacterales in Italy

Background and Objective Aztreonam-avibactam (ATM-AVI) is a novel combination antibiotic approved in Europe for the treatment of complicated intra-abdominal infection, hospital-acquired pneumonia, including ventilator-associated pneumonia; complicated urinary tract infection, including pyelonephritis and for infections due to aerobic Gram-negative organisms with limited treatment options. This analysis assessed the cost effectiveness of ATM-AVI ± metronidazole versus colistin + meropenem (COL + MER) for the treatment of patients with complicated intra-abdominal infection and hospital-acquired pneumonia/ventilator-associated pneumonia, including infections with suspected metallo-β-lactamase-producing Enterobacterales from the public payer perspective in Italy using phase III trial data. Methods The cost-effectiveness analysis adopted a decision tree model to simulate the clinical pathway of complicated intra-abdominal infection and hospital-acquired pneumonia/ventilator-associated pneumonia, followed by a Markov model to capture lifetime health outcomes on cured patients, with costs valued in 2024 Euros and discounted at 3%. The model captures the impact of resistant pathogens and side effects (i.e. nephrotoxicity). Model uncertainty was assessed using a probabilistic and deterministic sensitivity analysis. Results The ATM-AVI treatment sequence (ATM-AVI ± metronidazole followed by cefiderocol after treatment failure) had improved clinical outcomes and higher cure rates, shorter hospital stays and higher quality-adjusted life-year gains compared with the COL + MER sequence (COL + MER followed by cefiderocol after treatment failure). The incremental cost-effectiveness ratio in the ATM-AVI sequence was dominant for complicated intra-abdominal infection and was €1552 per quality-adjusted life-year for hospital-acquired pneumonia/ventilator-associated pneumonia, well below the willingness-to-pay threshold of €30,000 in Italy. Conclusions Our analysis suggests that ATM-AVI is expected to be a cost-effective use of Italian healthcare resources for treating suspected metallo-β-lactamase-producing Enterobacterales, including complicated intra-abdominal infection and hospital-acquired pneumonia/ventilator-associated pneumonia.