SULBACTAM-DURLOBACTAM, A PATHOGEN-TARGETED ANTIMICROBIAL
nephrotoxicity, infections, Injury, Failure, Loss, and End-Stage Kidney, RIFLE
COMPLICATED URINARY TRACT INFECTION, INFECTIONS, ACUTE PYELONEPHRITIS
The development of sulbactam-durlobactam (SUL-DUR) is a pathogen-targeted response to infections caused by A number of reports describe the in vitro antibacterial activity of SUL-DUR against contemporary clinical isolates of ABC [The tolerability and PK of SUL-DUR were also investigated in 6 phase 1 studies in healthy volunteers and in a phase 2 study of hospitalized patients with complicated urinary tract infection or acute pyelonephritis [SUL-DUR met the primary efficacy endpoint of noninferiority for 28-day all-cause mortality in the primary analysis population (part A) and CRAB microbiologically modified intention-to-treat population (n = 125). Mortality in the SUL-DUR group was 19.0% (12/63) versus 32.2% (20/62) in the colistin group (treatment difference: −13.2%; 95% confidence interval: −30.0%, 3.5%; noninferiority margin: 20%). In all study populations, similar trends favoring SUL-DUR were observed in 14-day and 28-day all-cause mortality. Clinical cure rates at Test of Cure were 61.9% for SUL-DUR and 40.3% for colistin. Furthermore, the 28-day all-cause mortality in part B was 17.9%, consistent with that observed in part A.The primary safety objective of the ATTACK trial was a comparison of the incidence of nephrotoxicity as measured by the Risk, Injury, Failure, Loss, and End-Stage Kidney (RIFLE) classification in part A [ATTACK was the first randomized controlled trial to evaluate an investigational antibiotic against a specific drug-resistant gram-negative pathogen. SUL-DUR is the first investigational drug to demonstrate efficacy in a 28-day all-cause mortality trial focused on CRAB. These positive results have facilitated the continued development of SUL-DUR towards the ultimate goal of global regulatory approval.