An international team of investigators this week published phase 3 clinical trial data supporting aztreonam-avibactam as a potential therapeutic option for patients with serious gram-negative bacterial infections with limited treatment options.
Jointly developed by Pfizer and Abbvie, aztreonam-avibactam is a beta-lactam/beta-lactamase inhibitor combination that restores aztreonam's activity against gram-negative bacteria that carry two defense mechanisms—metallo-beta-lactamase (MBL) and beta-lactamase enzymes—that confer resistance to nearly all currently available antibiotics. It was approved in April by the European Medicines Agency based on the results of two phase 3 clinical trials that evaluated its efficacy in treating several types of multidrug-resistant infections.
The results of the open-label REVISIT trial, published in The Lancet Infectious Diseases, show that aztreonam-avibactam had similar clinical cure rates as meropenem in 422 patients with either complicated intra-abdominal infection (76.4% vs 74.0%, respectively) or hospital-acquired/ventilator-associated pneumonia (HAP-VAP) (45.9% vs 41.7%) caused by gram-negative bacteria. The investigators also found that overall all-cause mortality rates at 28 days were relatively low, and similar between both treatment groups for each infection type (2% for aztreonam-avibactam vs 3% for meropenem in patients with complicated intra-abdominal infection and 11% vs 19% in patients with HAP-VAP).
Aztreonam-avibactam was generally well-tolerated, with safety findings that were consistent with the known safety profile of aztreonam.
"These phase 3 efficacy and safety data provide support for aztreonam-avibactam as a potential therapeutic option for complicated intra-abdominal infection or HAP-VAP caused by Gram-negative bacteria," the investigators wrote.
Trial limitations
The investigators add, however, that while the trial was conducted in a region where MBL-producing gram-negative pathogens are prevalent, few patients in the trial had infections caused by MBL-producing bacteria, highlighting the need for more data on the drug's efficacy against such pathogens. That concern is echoed in a commentary by infectious disease experts from the University of Maryland School of Pharmacy and the University of Pittsburgh.
"Ultimately, the small number of patients with metallo-β-lactamases in the study restricts the ability to draw conclusions about the utility of aztreonam-avibactam in eradicating these difficult-to-treat pathogens," Emily Heil, PharmD, and Erin McCreary, PharmD wrote.
