Several recently published guidelines regarding the treatment of C. difficile infection recommend vancomycin as first-line antibiotic treatment. However, given the recent increase in severity and frequency of C. difficile infections, there is a critical need for novel C. difficile therapies. Cadazolid is a novel quinoxolidinone antibiotic that acts in the intestinal lumen by inhibiting bacterial protein synthesis, and was shown to have similar efficacy to vancomycin in the treatment of C. difficile in a phase 2 trial; a phase 3 trial has not yet been conducted. In two identically designed, phase 3, randomized, controlled non-inferiority studies (IMPACT 1 and IMPACT 2), a total of 1,263 patients with mild-to-moderate or severe C. difficile infection were assigned to receive cadazolid or vancomycin to study clinical cure, defined as the resolution of diarrhea for two days after the end of treatment with no additional treatment for C. difficile infection. In both trials, patients in the vancomycin group had a higher percentage of epidemic strains. Based on a modified intention-to-treat population, cadazolid was found to be noninferior to vancomycin in the incidence of clinical cure in IMPACT 1 (84% in the cadazolid group vs. 85% in the vancomycin group, treatment difference -1.4, 95% CI -7.2 to 4.3). However, cadazolid was not noninferior to vancomycin in the incidence of clinical cure in IMPACT 2 (81% in the cadazolid group vs. 86% in the vancomycin group, treatment difference -4.7, 95% CI -10.7 to 1.3). In both studies, cadazolid had a similar safety profile to vancomycin. Overall, non-inferiority of cadazolid compared with vancomycin for C. difficile infection was only shown in one of two studies. Further investigation of cadazolid for the treatment of C. difficile infections will likely not be pursued.
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