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


METHODS
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.


RESULTS
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.


CONCLUSIONS
REP3123 demonstrated good potency against C. difficile, but limited activity against many other intestinal anaerobic species, thus, in theory, maintaining the colonization resistance barrier.
Citron
Diane M
DM
R. M. Alden Research Laboratory, Culver City, CA 90230, USA. d.m.citron@att.net
Warren
Yumi A
YA
Tyrrell
Kerin L
KL
Merriam
Vreni
V
Goldstein
Ellie J C
EJ
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001421:Bacteria, Anaerobic / Q000187:drug effects* / Q000302:isolation & purification; D001578:Benzopyrans / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000382:microbiology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D013876:Thiophenes / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001578:Benzopyrans; D004791:Enzyme Inhibitors; C541771:REP 3123; D013876:Thiophenes