Vol.67 No.3 May 2019
A review of novel drug therapies for Clostridioides (Clostridium) difficile infection
Department of General Internal Medicine, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, Japan
Abstract
The rising incidence of Clostridioides difficile infection (CDI) in the last two decades and the associated high mortality rate have made this infection one of the most important healthcare challenges of the current era. Until now, only two antimicrobial agents, metronidazole (MNZ) and vancomycin (VCM), have been used clinically to treat CDI. Several new antibiotics and non-antimicrobial therapies, such as monoclonal antitoxin antibodies, fecal microbial transplantation (FMT) and vaccination, are being developed to combat CDI. In Japan, fidaxomicin (FDX) and bezlotoxumab received were approved for the treatment and prevention of CDI last year. FDX, which has already been used in the US and European countries, is a novel macrocyclic antibiotic that inhibits bacterial RNA synthesis by impairing bacterial RNA polymerase activity. FDX has been demonstrated to be non-inferior to VCM for the treatment of CDI and to be more effective than VCM for reducing the recurrence rate of CDI. Bezlotoxumab is a monoclonal antibody against C. difficile toxin B. It has been demonstrated to substantially reduce the rate of recurrent infections as compared to placebo. Furthermore, clinical trials of novel antimicrobials, such as cadazolid, surotomycin, ridinilazole, ramoplanin, LFF571 and CRS3123, have also been conducted recently. These antimicrobial agents are orally administered and accumulate at high concentrations in the intestinal tract as they are characterized by poor absorption from the intestine. As FMT has been shown to be effective in preventing CDI recurrence, development and clinical studies of live biotherapeutic drugs such as RBX2660 and SER109 have also been conducted. Practical application of these novel therapies is expected soon. However, the available epidemiological data on CDI in Japan are insufficient, and more data are needed. In this review, we discuss the different therapeutic agents, including the newly developed and currently available drugs, used to treat CDI.
Key word
Clostridioides（Clostridium）difficile, antimicrobial agent, fidaxomicin, bezlotoxumab
Received
September 18, 2018
Accepted
November 28, 2018
Jpn. J. Chemother. 67 (3): 324-330, 2019
