In vitro activity of pentamidine against Tropheryma whipplei

Abstract

Pentamidine is a group I intron splice inhibitor used as a chemotherapeutic agent to treat parasitic infections. It was recently found to be efficient intracellularly against Coxiella burnetii, the bacterial agent of Q fever. This in vitro activity was linked to the presence of self-splicing group I introns that disrupt the 23S rRNA of C. burnetii. However, there are several indications that pentamidine may have a wider range of antibacterial activity. The aim of this study was to determine the in vitro activity of pentamidine against Tropheryma whipplei, the agent of Whipple's disease, a chronic disease for which antibiotic treatment remains challenging. In vitro susceptibility testing of pentamidine and doxycycline was assessed both in axenic medium and in cell culture against three clinical isolates of T. whipplei using a quantitative real-time polymerase chain reaction (PCR) assay as previously described. Both doxycycline and pentamidine were found to be active against T. whipplei strains both in axenic medium and in cell culture, with minimum inhibitory concentration ranges of 0.5–1 mg/L and 0.125–0.25 mg/L for doxycycline and pentamidine, respectively. Pentamidine was effective in vitro against T. whipplei both intracellularly and in axenic medium. This is the first evidence of the direct efficacy of pentamidine against T. whipplei grown in axenic medium and in cells. Since pentamidine has been widely used in humans, we believe that it could be an alternative drug for the treatment of this chronic disease that should be further studied in clinical trials.