Sub-lethal doses of surotomycin and vancomycin have similar effects on Clostridium difficile virulence factor...

Clostridium difficile is an anaerobic spore-forming bacterial pathogen that causes a spectrum of illness severity ranging from mild diarrhoea to severe life-threatening pseudomembranous colitis. C. difficile infection (CDI) is antibiotic-associated and primarily mediated by two exotoxins, Toxins A and B. We and others have shown that some antibiotics stimulate Toxin A and B production by C. difficile in a strain-specific manner. Still, the effects of newer anti-C. difficile antibiotics on this process and spore formation remain to be investigated.

Surotomycin (formally CB-183,315) is a novel, minimally absorbed, narrow-spectrum antibiotic. We determined the effects of surotomycin on C. difficile growth, toxin production and sporulation in historical and BI/NAP1/027 epidemic strains of C. difficile.Results/Key findings. While antibiotic free controls showed toxin production during the stationary phase growth, all strains exposed to sub-inhibitory concentrations of surotomycin and vancomycin demonstrated increased TcdA and TcdB production during early (log phase) growth by all strains. However, this effect was not observed at 24 or 48 h post-treatment by any of the C. difficile strains exposed to either antibiotic. Additionally, all doses of surotomycin and vancomycin suppressed spore formation in all tested strains.

In summary, these findings demonstrate that surotomycin and vancomycin have similar effects on exotoxin production and sporulation by C. difficile in vitro. Furthermore, since spores contribute to recurrent infection, the ability of surotomycin to suppress spore formation may explain its ability to disrupt the reinfection cycle in the clinical setting.