Alternative therapies for Clostridium difficile infections

Clostridium difficile infection is a serious condition responsible for significant morbidity and mortality, especially in patients being treated with antimicrobials. Increasing frequency of the infection and hypervirulent C. difficile strains have resulted in more severe disease as well as therapeutic failures with traditional treatment (metronidazole and vancomycin). To review the studies assessing nontraditional therapies for the prevention and treatment of primary or recurrent C. difficile infection, we conducted a literature search of the PubMed-MEDLINE databases (1984-2010). Of the 98 studies identified, 21 met our inclusion criteria. Five clinical trials and one retrospective medical record review evaluated probiotic or prebiotic formulations for the prevention of C. difficile infection. Only one of these studies, which included Lactobacillus casei and L. bulgaricus in the probiotic formulation, showed efficacy. Ten clinical trials evaluated treatment of an initial episode of C. difficile infection (primary treatment) with the anti-microbials fidaxomicin, fusidic acid, rifampin, teicoplanin, and nitazoxanide, as well as the toxin-binding polymer, tolevamer. Only nitazoxanide and teicoplanin demonstrated noninferiority when compared with vancomycin or metronidazole. Four prospective studies and one retrospective study evaluated treatment of relapsing C. difficile infection. Prebiotic formulations for the prevention and treatment of recurrent C. difficile infection have not proved to be clinically warranted. Nitazoxanide, teicoplanin, and fidaxomicin may be considered as alternatives to traditional treatment; however, clinical experience is limited with these agents for this indication. Bacteriotherapy with fecal instillation has demonstrated high clinical cure rates in case studies and in a retrospective study; however, to our knowledge, randomized clinical trials are lacking for this therapeutic approach. As C. difficile infection rates continue to increase and hypervirulent strains continue to emerge, it is important for future clinical studies to assess alternative therapies.