Increasing antimicrobial resistance among pathogens that cause complicated intra-abdominal infections (cIAI) supports the development of new antimicrobials. Eravacycline, a novel member of the fluorocycline family, is active against multidrug-resistant bacteria including extended-spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae (CRE).
IGNITE4 was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either eravacycline 1 mg/kg q12h or meropenem 1 g q8h intravenously for 4–14 days. The prospectively defined primary objective was to demonstrate statistical noninferiority in clinical cure rates at the test-of-cure visit (25–31 days from start of therapy) in the micro-ITT population using a noninferiority margin of –12.5%. Microbiological outcomes and safety were also evaluated.
Eravacycline was noninferior to meropenem in the primary endpoint (177/195 [90.8%] vs 187/205 [91.2%]; difference –0.5%; 95% confidence interval [CI] –6.3 to 5.3), exceeding the prespecified margin. Secondary endpoints included clinical cure rates in the modified intent-to-treat population (231/250 [92.4%] vs 228/249 [91.6%]; (difference 0.8; CI -4.1, 5.8) and the clinically evaluable population (218/225 [96.9%] vs 222/231 [96.1%]; (difference 0.8; CI -2.9, 4.5). In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 87.5% (14/16) and 84.6% (11/13) in the eravacycline and meropenem groups, respectively. Eravacycline in this and our previous trials saw relatively low rates of adverse events (AEs) for a drug of this class, with less than 5%, 4%, and 3% of patients experiencing nausea, vomiting, and diarrhea, respectively.
Treatment with eravacycline was noninferior to meropenem in adult patients with cIAI, including infections caused by resistant pathogens.