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

Objectives 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. diffici...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2009-05, Vol.63 (5), p.972-976
Main Authors: Citron, Diane M., Warren, Yumi A., Tyrrell, Kerin L., Merriam, Vreni, Goldstein, Ellie J. C.
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacteria
Bacteria, Anaerobic - drug effects
Bacteria, Anaerobic - isolation & purification
Benzopyrans - pharmacology
Biological and medical sciences
Brucella
C. difficile infection
Clostridium difficile
Clostridium ramosum
colonization resistance
Comparative studies
Enzyme Inhibitors - pharmacology
Gastroenterology
Gastrointestinal Tract - microbiology
Gram-Positive Bacteria - drug effects
Gram-Positive Bacteria - isolation & purification
Humans
Inhibitor drugs
Lactobacillus
Medical sciences
Microbial Sensitivity Tests
normal gut flora
Pharmacology. Drug treatments
Ribonucleic acid
RNA
Thiophenes - pharmacology
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Summary:Objectives 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.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkp037