The US Food and Drug Administration (FDA) yesterday approved the combination antibiotic sulbactam-durlobactam for the treatment of patients with hospital-related bacterial pneumonia caused by a highly resistant superbug.
The drug, marketed as Xacduro, combines a beta-lactam antibiotic (sulbactam) with a novel, broad-spectrum beta-lactamase inhibitor (durlobactam) and specifically targets susceptible strains of Acinetobacter baumannii-calcoaceticus complex.
These bacteria, which have been labeled a critical-priority pathogen by the World Health Organization and an urgent threat by the US Centers for Disease Control and Prevention, harbor resistance genes for multiple antibiotic classes and cause severe and life-threatening infections in hospitalized patients.
The FDA approved Xacduro for treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) based on the results of a phase 3 trial that showed the drug was statistically non-inferior to colistin in 177 patients hospitalized with pneumonia caused by carbapenem-resistant A baumannii (CRAB) and was well tolerated. Of the patients who received Xacduro, 19% died within 28 days of treatment, compared with 32% of those treated with colistin.
The approval, granted to Entasis Therapeutics (now a subsidiary of Innoviva Specialty Therapeutics), comes a little more than a month after the FDA's Antimicrobial Drug Advisory Committee voted 12-0 to support approval.
"Today's approval helps address a high unmet medical need by providing an additional treatment option for some of the sickest patients in our nation's hospitals," Peter Kim, MD, director of the Division of Anti-Infectives at the FDA's Center for Drug Evaluation and Research, said in an FDA press release.
Limited treatment options
Experts say Xacduro will be a welcome addition to what is currently a limited set of options for treatment of CRAB infections, which typically occur in healthcare settings and are associated with more than 300,000 deaths globally each year. Mortality rates for CRAB infections, the majority of them pneumonia, are close to 50%.
"Of all the bacterial pathogens responsible for human infections, carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most concerning," Richard Watkins, MD, of Northeast Ohio Medical University, and Robert Bonomo, MD, of Case Western Reserve University School of Medicine, wrote in an article published earlier this month in Clinical Infectious Diseases. "The increased mortality from CRAB infections and the limited treatment options that are currently available contribute to this concern."
Of all the bacterial pathogens responsible for human infections, carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most concerning.
Bonomo and Watkins note that while sulbactam has been commonly used in combination with other antibiotics against CRAB because of its ability to kill A baumannii, it is degraded by the wide variety of beta-lactamase enzymes produced by Acinetobacter species as a defense mechanism. Durlobactam protects sulbactam from those enzymes. The combination is administered by intravenous infusion.
"SUL-DUR [sulbactam-durlobactam], if approved, represents a very welcome addition to our antibiotic armamentarium," they wrote. "Its novel characteristics and encouraging clinical data suggest SUL-DUR will likely play a role in the management of infections caused by CRAB."