Aztreonam–Avibactam for Patients Who are Critically Ill with Gram-Negative Bacterial Infections: Comparison with Colistin Plus Meropenem Subgroup from the Phase 3 REVISIT Study

INTRODUCTION: The phase 3 REVISIT trial evaluated aztreonam-avibactam versus meropenem ± colistin for complicated intra-abdominal infection (cIAI), hospital-acquired pneumonia (HAP), or ventilator-associated pneumonia (VAP). This descriptive post hoc analysis explored efficacy and safety of aztreonam-avibactam versus colistin plus meropenem in patients with cIAI or HAP/VAP. METHODS: This post hoc analysis included patients who received colistin plus meropenem (all with baseline Acute Physiology and Chronic Health Evaluation II [APACHE II] scores ≥ 8) and patients who received aztreonam-avibactam with baseline APACHE II scores ≥ 8, for comparable baseline severity. The primary efficacy endpoint was adjudicated clinical cure rate at the test-of-cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) analysis sets. Secondary endpoints included clinical cure rate at TOC by infection type, favorable microbiological response at TOC, 28-day mortality, and safety. Efficacy and safety outcomes were compared descriptively. RESULTS: Overall, we included 186 patients in the ITT population (aztreonam-avibactam, n = 160; colistin plus meropenem, n = 26). Clinical cure rates (95% CI) were 63.1% (55.5-70.3) and 53.8% (35.1-71.8) for aztreonam-avibactam and colistin plus meropenem, respectively (ITT). Results were similar in the CE analysis set. Clinical cure rates in both cIAI and HAP/VAP subgroups were consistent with the overall results, although 95% CIs were wide and the number of patients treated with colistin plus meropenem was small. Microbiological response rate was 71.7% for aztreonam-avibactam and 46.7% for colistin plus meropenem (microbiological ITT). Twenty-eight-day mortality was similar for aztreonam-avibactam (7.5%) and colistin plus meropenem (11.5%; ITT). Proportions of patients with all-cause adverse events (AEs) and serious AEs were generally similar in both groups, with fewer treatment-related AEs for aztreonam-avibactam. CONCLUSIONS: This exploratory post hoc analysis provides further insights into the efficacy and safety of aztreonam-avibactam versus colistin plus meropenem in patients with cIAI or HAP/VAP who were critically ill. CLINICAL TRIAL REGISTRATION: NCT number: NCT03329092.