Update of treatment algorithms for Clostridium difficile infection

Clostridium difficile is the leading cause of antibiotic-associated diarrhea, both in healthcare facilities and the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the ESCMID guidance document on CDI treatment in 2014, new therapeutic approaches have been developed and tested to achieve higher sustained clinical cure in CDI. To review novel treatments and approaches for CDI, except probiotics and vaccines. We focused on new antibiotics, antibiotic inactivators, monoclonal antibodies (mAbs), and gut microbiota modulating therapies. A literature review was performed for clinical trials published in Pubmed, Embase, or Cochrane library between January 2013 and November 2017. We analyzed 28 clinical trials and identified 14 novel agents. Completed phase II studies were found for cadazolid, LFF571, ridinilazole, and non-toxigenic C. difficile strains. Four phase III active comparator studies comparing vancomycin with bezlotoxumab, surotomycin (n=2), and rifaximin have been published. Seven clinical trials for treatment of multiple recurrent CDI with fecal microbiota transplantation (FMT) were analyzed, describing FMT by upper or lower gastrointestinal route (n=5) or by capsules (n=2). Metronidazole is mentioned in the ESCMID guideline as first line therapy, but we propose that vancomycin orally will become the first choice when antibiotic treatment for CDI is necessary and the severity of the disease difficult to assess. Fidaxomicin is an good alternative, especially in patients at risk to develop a relapse. Vancomycin combined with FMT remains the primary therapy for multiple recurrent CDI . We anticipate that new medication that protects the gut microbiota will be further developed and tested to prevent CDI during antibiotic therapy