Antibiotics combo promising against multidrug-resistant bacterial infections: Result from two phase 3 trials

Pfizer announced the positive results from two phase 3 trials; the trials evaluated the investigational antibiotic combination in treating multidrug-resistant bacterial infections. According to company officials, the results will form the basis for regulatory filings later this year in the European Union, United States, United Kingdom, and China.

Data support that ATM-AVI is well-tolerated and effective, with no new safety findings and a safety profile comparable to aztreonam alone.

"We believe these data demonstrate that ATM-AVI, if approved, could be a crucial 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 said in a press release. "We are committed to meeting this critical need and helping to address the global health threat of antimicrobial resistance."

The phase 3 REVISIT study made a comparison between ATM-AVI ± metronidazole (MTZ) with meropenem (MER) with or without colistin (COL) for treating ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP), and intra-abdominal infections (cIAI) among in 422 hospitalized patients in 20 countries.

Key findings include:

· For patients with cIAI, the cure rate in the intention-to-treat (ITT) analysis was 76.4% for patients in the ATM-AVI treatment arm and 74.0% for patients in the meropenem arm, with a treatment difference of 2.4%.

· In the clinically evaluable (CE) analysis, the cure rate was 85.1% vs 79.5%.

· For HAP/VAP patients, the ITT cure rate was 45.9% for ATM-AVI and 41.7% for meropenem (treatment difference, 4.3%) and the CE cure rate was 46.7% vs 54.5%.

· All-cause 28-day mortality rates for cIAI patients were 1.9% in the ATM-AVI group and 2.9% for meropenem, and 10.8% for ATM-AVI versus 19.4% for meropenem in HAP/VAP patients.

· ATM-AVI was well-tolerated, with a similar incidence of serious adverse events (19.3%) as in the meropenem treatment arm (18.2%)

In the ASSEMBLE trial, the researchers compared ATM-AVI with the best available therapy (BAT) in 15 patients in nine countries with infections due to confirmed MBL-producing gram-negative bacteria.

The findings revealed that 41.7% of patients in the ATM-AVI arm were cured at test-of-cure, compared with none in the BAT arm. None of the patients treated with ATM-AVI experienced a treatment-related serious adverse event.

"These data are promising given the complexities of managing cIAI and HAP/VAP infections in these hospitalized, critically ill patients, and the challenges of real-world patient recruitment within this population," said Yehuda Carmeli, MD, MPH, head of the National Institute for Antibiotic Resistance and Infection Control at Tel Aviv Medical Center in Israel, in the news release.