The US Food and Drug Administration approved Xacduro (sulbactam durlobactam for injection), a new treatment for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) caused by susceptible strains of bacteria called Acinetobacter baumannii -calcoaceticus complex , for patients over 18 years of age.
According to the World Health Organization, Acinetobacter species top the list of critical bacterial pathogens that pose the greatest threat to human health, highlighting the high level of need for additional treatment options amid growing global resistance to antimicrobial medications.
"The FDA is dedicated to supporting the development of safe and effective treatment options for infections caused by difficult-to-treat bacteria such as Acinetobacter baumannii-calcoaceticus complex," said Peter Kim, MD, MS, director of the Division of Anti-Infectives at the Center of FDA Drug Evaluation and Research. “Today’s approval helps address a large unmet medical need by providing an additional treatment option for some of the sickest patients in our nation’s hospitals.”
The Acinetobacter baumannii-calcoaceticus complex (hereinafter referred to as A. baumannii) includes four species of bacteria in the Acinetobacter family. These bacteria can cause infections in various parts of the body, occurring most frequently in healthcare settings and predominantly causing pneumonia. A. baumannii can become highly resistant to multiple antibacterial drugs and current treatment options for drug-resistant A. baumannii are limited.
Xacduro consists of sulbactam, a drug structurally related to penicillin, and durlobactam. Sulbactam kills A. baumannii, while durlobactam protects sulbactam from degradation by enzymes that A. baumannii can produce. Xacduro is administered by intravenous infusion .
The efficacy of Xacduro was established in a multicenter, active-controlled, open-label (investigator unblinded, evaluator blinded) non-inferiority clinical trial in 177 adults hospitalized with pneumonia caused by carbapenem-resistant A. baumannii. Patients received Xacduro or colistin (a comparator antibiotic) for up to 14 days. Both treatment arms also received an additional antibiotic, imipenem/cilastatin , as background therapy for potential HABP/VABP pathogens other than the Acinetobacter baumannii-calcoaceticus complex. The primary measure of efficacy was all-cause mortality within 28 days of treatment in patients with confirmed carbapenem-resistant A. baumannii infection.
Of patients receiving Xacduro, 19% (12 of 63 patients) died, compared with 32% (20 of 62 patients) receiving colistin; this demonstrated that Xacduro was non-inferior to colistin.
The most common adverse reaction with Xacduro was abnormalities in liver function tests. Xacduro comes with certain warnings and precautions, such as hypersensitivity reactions and Clostridioides, C. difficile-associated diarrhea.
Patients should not receive Xacduro if they have a history of known severe hypersensitivity to the components of Xacduro, sulbactam, or other beta-lactam antibacterial drugs.
The FDA granted Xacduro Fast Track, Infectious Disease Qualified Product and Priority Review designations for this application. The FDA granted approval of Xacduro to Entasis Therapeutics.
