RESUMEN
INTRODUCTION: Imipenem/cilastatin/relebactam (IMI/REL), a combination ß-lactam antibiotic (imipenem) with a novel ß-lactamase inhibitor (relebactam), is an efficacious and well-tolerated option for the treatment of hospitalized patients with gram-negative (GN) bacterial infections caused by carbapenem-non-susceptible (CNS) pathogens. This study examines cost-effectiveness of IMI/REL vs. colistin plus imipenem (CMS + IMI) for the treatment of infection(s) caused by confirmed CNS pathogens. METHODS: We developed an economic model comprised of a decision-tree depicting initial hospitalization, and a Markov model projecting long-term health and economic impacts following discharge. The decision tree, informed by clinical data from RESTORE-IMI 1 trial, modeled clinical outcomes (mortality, cure rate, and adverse events including nephrotoxicity) in the two comparison scenarios of IMI/REL versus CMS + IMI for patients with CNS GN infection. Subsequently, a Markov model translated these hospitalization stage outcomes (i.e., death or uncured infection) to long-term consequences such as quality-adjusted life years (QALYs). Sensitivity analyses were conducted to test the model robustness. RESULTS: IMI/REL compared to CMS + IMI demonstrated a higher cure rate (79.0% vs. 52.0%), lower mortality (15.2% vs. 39.0%), and reduced nephrotoxicity (14.6% vs. 56.4%). On average a patient treated with IMI/REL vs. CMS + IMI gained additional 3.7 QALYs over a lifetime. Higher drug acquisition costs for IMI/REL were offset by shorter hospital length of stay and lower AE-related costs, which result in net savings of $11,015 per patient. Sensitivity analyses suggested that IMI/REL has a high likelihood (greater than 95%) of being cost-effective at a US willingness-to-pay threshold of $100,000-150,000 per QALY. CONCLUSIONS: For patients with confirmed CNS GN infection, IMI/REL could yield favorable clinical outcomes and may be cost-saving-as the higher IMI/REL drug acquisition cost is offset by reduced nephrotoxicity-related cost-for the US payer compared to CMS + IMI.
RESUMEN
INTRODUCTION: The clinical efficacy and safety of ceftolozane/tazobactam for the treatment of ventilated hospital-acquired bacterial pneumonia (vHABP) and ventilator-associated bacterial pneumonia (VABP) has been demonstrated in the phase III randomised controlled trial ASPECT-NP. However, there are no published data on the cost-effectiveness of ceftolozane/tazobactam for vHABP/VABP. These nosocomial infections are associated with high rates of morbidity and mortality, and are increasingly complicated by growing rates of resistance and the inappropriate use of antimicrobials. This study is to assess the cost-effectiveness of ceftolozane/tazobactam compared with meropenem for the treatment of vHABP/VABP in a US hospital setting. METHODS: A short-term decision tree followed by a long-term Markov model was developed to estimate lifetime costs and quality-adjusted life-years associated with ceftolozane/tazobactam and meropenem in the treatment of patients with vHABP/VABP. Pathogen susceptibility and clinical efficacy were informed by the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database and ASPECT-NP, respectively. A US healthcare sector perspective was adopted, capturing direct costs borne by third-party payers or integrated health systems, and direct health effects for patients. RESULTS: In the confirmed treatment setting (post-susceptibility results), the incremental cost-effectiveness ratio for ceftolozane/tazobactam compared to meropenem was US$12,126 per quality-adjusted life-year (QALY); this reduced when used in the early treatment setting (before susceptibility results) at $4775/QALY. CONCLUSION: Ceftolozane/tazobactam represents a highly cost-effective treatment option for patients with vHABP/VABP versus meropenem when used in either the confirmed or early treatment setting; with increased cost-effectiveness shown in the early setting.