P-105. Aztreonam-Avibactam Compared with Adjunctive Colistin Combined with Meropenem for the Treatment of Serious Gram-Negative Bacterial Infections: Subgroup Analysis of the Phase 3 REVISIT Study

Background

In the phase 3 REVISIT trial, efficacy of aztreonam-avibactam ± metronidazole (ATM-AVI ± MTZ) was similar to meropenem ± colistin (MER ± COL) in patients with complicated intra-abdominal infection (cIAI) or hospital-acquired/ventilator-associated pneumonia (HAP/VAP) caused by Gram-negative bacteria, including metallo-β-lactamase producers. This exploratory analysis evaluated efficacy and safety in the subset of patients who received adjunctive COL combined with MER compared with a subgroup of ATM-AVI patients with similar baseline characteristics.

Adjudicated clinical cure rates at the TOC visit for ATM-AVI ± MTZa and MER + COL subgroups (ITT and CE analysis sets)

Methods

REVISIT was a prospective, randomized (2:1), multicenter, open-label, central assessor-blinded study. In the intent-to-treat analysis set, 26 patients in the MER group (n=140) received adjunctive COL. In the ATM-AVI [+ MTZ for cIAI only] group (n=282), 160 patients with baseline Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥ 8 (the minimum value in the MER + COL subgroup) were selected for descriptive comparison (no formal hypothesis testing).

Summary of AEs and SAEs in the ATM-AVI ± MTZa and MER + COL subgroups (safety analysis set)

Results

The ATM-AVI (APACHE II score ≥ 8) and MER + COL subgroups were well-balanced for demographic and baseline characteristics including sex, median age and creatinine clearance; approximately 40% of patients in both subgroups had prior antibiotic treatment failure. Adjudicated clinical cure rates at test-of-cure, the primary efficacy endpoint, numerically favored the ATM-AVI subgroup overall and by infection type, with wide 95% CIs reflecting the small number of patients treated with COL (Table 1). The proportions of patients with all-cause and treatment-related adverse events (AEs), AEs leading to treatment discontinuation, and serious AEs were generally similar across subgroups (Table 2).

Conclusion

In line with the overall REVISIT trial results, ATM-AVI (± MTZ) showed similar effectiveness as adjunctive COL with MER in adults with cIAI or HAP/VAP, and was generally well tolerated.

Disclosures

Heidi Leister-Tebbe, BSN, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Yehuda Carmeli, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Qpex: Advisor/Consultant|Qpex: Grant/Research Support|Qpex: Honoraria|Roche: Advisor/Consultant|Roche: Grant/Research Support|Roche: Honoraria Georgios L. Daikos, PhD, MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Viatris: Honoraria Ying Ma, MD, Pfizer: Employee and Shareholder|Pfizer: Stocks/Bonds (Public Company) Wenjuan Xu, MD, Pfizer: Employee and shareholder|Pfizer: Stocks/Bonds (Public Company) Michele Wible, MS, Pfizer: Employee and shareholder|Pfizer: Stocks/Bonds (Public Company) Joanne Leaney, PhD, Pfizer: Employee and shareholder|Pfizer: Stocks/Bonds (Public Company)