2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study
Yehuda Carmeli, Jose-Miguel Cisneros, Mical Paul, Georgios Daikos, Minggui Wang, Julián Torre Cisneros, George Singer, Ivan Titov, Illia Gumenchuk, Yongjie Zhao, Rosa-María Jiménez Rodríguez, Lu Liang, Gang Chen, O. V. Pyptіuk, Firdevs Aksoy, Halley Rogers, Michele Wible, Francis F. Arhin, Alison Luckey, Joanne L. Leaney, Rienk Pypstra, Joseph W. Chow
Abstract
Abstract Background Multidrug resistant (MDR) Gram-negative bacteria, including metallo-β-lactamase (MBL) producers, pose significant treatment challenges. This study investigated efficacy and safety of aztreonam-avibactam (ATM-AVI) in the treatment of complicated intra-abdominal infection (cIAI) or hospital-acquired)/ventilator-associated pneumonia (HAP/VAP) due to Gram-negative bacteria, including MBL-producing MDR pathogens, with limited or no treatment options. Methods REVISIT was a phase 3, prospective, randomized, multicenter, open-label, central assessor-blinded study in hospitalized adults. Patients were randomized 2:1 to ATM-AVI (± metronidazole [MTZ]; cIAI patients only) or meropenem (MER) ± colistin (COL) for 5–14 (cIAI) or 7–14 (HAP/VAP) days. Clinical cure at the test-of-cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) analysis sets were the primary efficacy endpoints. Key secondary endpoints included microbiological responses at TOC, 28-day mortality, and safety. No formal hypothesis testing was planned. Results In total, 422 patients were randomized (ATM-AVI ± MTZ, n=282; MER ± COL, n=140). Adjudicated clinical cure rates at TOC are shown in Table 1. Favorable microbiological response rates at TOC (micro-ITT analysis set) were 75.7% for ATM-AVI ± MTZ and 73.9% for MER ± COL; 28-day all-cause mortality rates for ATM-AVI ± MTZ and MER ± COL were 1.9% (4/208) vs 2.9% (3/104), and 10.8% (8/74) vs 19.4% (7/36) in cIAI and HAP/VAP, respectively. Adverse events (AEs) are summarized in Table 2. There were no treatment-related serious AEs in the ATM-AVI group. Conclusion ATM-AVI (± MTZ) was effective in treating patients with cIAI and HAP/VAP, displaying similar efficacy to MER ± COL. ATM-AVI was generally well tolerated. These data support potential use of ATM-AVI for the treatment of serious infections caused by susceptible Gram-negative bacteria. Further analyses will focus on MBL-producing pathogens. Trial registration. NCT03329092. Study sponsored by Pfizer. ATM-AVI is jointly developed with AbbVie, also supported by the United States Biomedical Advanced Research and Development Authority (BARDA) and the European Innovative Medicines Initiative (IMI), under the COMBACTE-CARE consortium. Disclosures 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 Rosa-María Jiménez Rodríguez, MD, PhD, Abex: Honoraria|B. Braun: Honoraria|Johnson & Johnson: Honoraria Halley Rogers, MPH, Pfizer: Ownership Interest Michele Wible, MS, Pfizer: Ownership Interest Francis Arhin, PhD, Pfizer: Ownership Interest Joanne Leaney, PhD, Pfizer: Ownership Interest Rienk Pypstra, MD, MBA, Pfizer: Stocks/Bonds Joseph Chow, MD, Pfizer: Ownership Interest