Sulbactam-Durlobactam Effective Against Hospital-Acquired ABC Infections

Treatment with the combination antibiotic sulbactam-durlobactam (SUL-DUR; Xacduro; Entasis Therapeutics) resulted in lower mortality and higher clinical cure and microbiological eradication compared with colistin in individuals with hospital-acquired Acinetobacter baumannii-calcoaceticus complex (ABC) infections.

Data from the phase 3 ATTACK clinical trial (NCT03894046) were presented at IDWeek 2023, October 11-14 in Boston, Massachusetts. SUL-DUR, which is an intravenous drug combining sulbactam, a beta-lactam antibacterial, and durlobactam, a beta-lactamase inhibitor, was recently approved by the FDA for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by Acinetobacter baumannii.

The phase 3, randomized, controlled, noninferiority trial compared SUL-DUR versus colistin in individuals with monomicrobial and polymicrobial ABC infections, randomly assigned to receive either 1.0 g sulbactam/1.0 g durlobactam IV infused over 3 hours every 6 hours plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour every 6 hours, or 2.5 mg/kg colistin IV infused over 30 minutes every 12 hours (after an initial loading dose of colistin 2.5 to 5 mg/kg) plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour every 6 hours, with a treatment duration of 7 to 14 days.

Overall, treatment with SUL-DUR reduced 28-day all cause mortality, the primary end point, by 13.2% compared with colistin (19%, 12/63 vs 32.3%, 20/62, respectively). Outcomes for individuals in the treatment arm were similar regardless of monomicrobial or polymicrobial ABC infections; however, individuals in the control arm with monomicrobial infections had higher mortality rates and worse clinical and microbiological outcomes than those with polymicrobial infections.

Among the 12 participants in the SUL-DUR arm who died, 4 were attributed to the index infection (33.3% each for mono- vs polymicrobial infection) compared with 10 in the control arm (46.7% monomicrobial vs 60% polymicrobial infection). Notably, 35% of patients treated with colistin who had monomicrobial ABC infection died compared with 17% in the SUL-DUR group.

A greater portion of those in the SUL-DUR arm reached clinical cure and favorable microbiological outcome at time of cure (7+2 days) compared with the colistin group (SUL-DUR: 64% clinical cure [mono] vs 59% [poly]; Colistin: 35% [mono] vs 53% [poly]; SUL-DUR: 67% favorable microbiological outcome [mono] vs 70% [poly]; Colistin: 33% [mono] vs 63% [poly]).

Further, 57% of co-infecting Gram-negative pathogens in the SUL-DUR arm at baseline were non-susceptible to imipenem; however, the addition of durlobactam restored susceptibility to 85% of those pathogens, including those with multi-drug resistance.

"These results suggest that SUL-DUR plus a carbapenem could be an effective treatment for polymicrobial infections that include ABC," the authors concluded, noting that "additional clinical data are needed to demonstrate efficacy."

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REFERENCE

McLeod S, Miller A, Shapiro AB, Rana K, Altarac D. Efficacy of Sulbactam-Durlobactam (SUL-DUR) Compared to Colistin (COL) against Acinetobacter baumannii-calcoaceticus Complex (ABC) Monomicrobial and Polymicrobial Infections in a Phase 3 Trial. Presented at: IDWeek 2023. October 11-14, 2023; Boston, MA. Abstract 85.