Aztreonam

The investigational antibiotic combination aztreonam-avibactam was found to be effective for treating serious bacterial infections caused by Gram-negative bacteria, according to findings from two phase 3 studies.

The REVIST (ClinicalTrials.gov Identifier: NCT03329092) and ASSEMBLE (ClinicalTrials.gov Identifier: NCT03580044) studies were conducted to evaluate the efficacy and safety of the novel antibiotic combination, which consists of a monobactam β-lactam (aztreonam) and a broad-spectrum β-lactamase inhibitor (avibactam).

REVIST included 422 hospitalized adult patients with complicated intraabdominal infections (cIAI), hospital-acquired pneumonia (HAP), or ventilator-associated pneumonia (VAP). Study participants were randomly assigned to receive aztreonam-avibactam ± metronidazole or meropenem ± colistin.

The clinical cure rates in the intention-to-treat analysis sets were reported to be 76.4% (95% CI, 70.3-81.8) and 45.9% (95% CI, 34.9-57.3) among patients with cIAI and HAP/VAP treated with aztreonam-avibactam ± metronidazole, respectively. In the clinically evaluable analysis set, the clinical cure rates were 85.1% (95% CI, 79.2-89.9) and 46.7% (95% CI, 32.7-61.1).

In the meropenem ± colistin arm, the clinical cure rates in the intention-to-treat population were 74.0% (95% CI, 65.0-81.7) and 41.7% (95% CI, 26.7-57.9) for cIAI and HAP/VAP infections, respectively. In the clinically evaluable analysis set, the clinical cure rates were 79.5% (95% CI, 69.9-87.1) and 54.5% (95% CI, 34.3-73.7).

Among cIAI patients, the all-cause mortality rates were 1.9% with aztreonam-avibactam ± metronidazole vs 2.9% with meropenem ± colistin. Among those with HAP/VAP, the all-cause mortality rates were 10.8% and 19.4% in the aztreonam-avibactam ± metronidazole and meropenem ± colistin groups, respectively.

These findings were further supported by results from the ASSEMBLE study, which included 15 adult patients and compared aztreonam-avibactam to best available therapy. At the test of cure visit, 41.7% (5/12) patients with infections due to confirmed metallo-β-lactamase (MBL)-producing Gram-negative bacteria were cured compared with none (0/3) of the patients on best available therapy.

Data from both trials also showed that the combination treatment was well tolerated and had a similar safety profile to aztreonam alone.

"We believe these data demonstrate that [aztreonam-avibactam], if approved, could be an important treatment option for patients with life-threatening bacterial infections that are resistant to almost all currently available antibiotics," said James Rusnak, Senior Vice President and Chief Development Officer, Internal Medicine, Anti-Infectives and Hospital, Pfizer. "We are committed to meeting this critical need and helping to address the global health threat of antimicrobial resistance."

Findings from REVIST and ASSEMBLE will form the basis of the regulatory submission for aztreonam-avibactam. The Company expects to submit the application with the Food and Drug Administration in the second half of 2023.

This article originally appeared on MPR

Phase 3 studies of Pfizer's novel antibiotic combination offer new treatment hope for patients with multidrug-resistant infections and limited treatment options. Pfizer. News release. June 1, 2023. https://www.businesswire.com/news/home/20230601005216/en/Phase-3-Studies-of-Pfizer%E2%80%99s-Novel-Antibiotic-Combination-Offer-New-Treatment-Hope-for-Patients-with-Multidrug-Resistant-Infections-and-Limited-Treatment-Options.