Comparative in vitro activity of REP3123 against Clostridium difficile and other anaerobic intestinal bacteria

The aim of this study was to determine the anaerobic spectrum of activity of REP3123, a novel diaryldiamine that inhibits bacterial methionyl-tRNA synthetases in Gram-positive bacteria. Fifty recent clinical isolates of Clostridium difficile from patients diagnosed with C. difficile infection and 223 other intestinal normal flora anaerobes were tested for their susceptibility to REP3123 and four or five comparator agents by the agar dilution method using supplemented Brucella agar with 5% laked sheep blood. All strains of C. difficile were inhibited by 0.5-1 mg/L REP3123, including those resistant to moxifloxacin and clindamycin. REP3123 lacked activity against many normal flora anaerobes in the gut, including Clostridium ramosum, bifidobacteria, lactobacilli of the Lactobacillus casei-rhamnosus-plantarum group and Gram-negative anaerobes. REP3123 demonstrated good potency against C. difficile, but limited activity against many other intestinal anaerobic species, thus, in theory, maintaining the colonization resistance barrier.