Probiotics for <i>Clostridium difficile</i>-associated disease

DOI
  • OKA Kentaro
    Tokyo R&D Center, Miyarisan Pharmaceutical Co., Ltd.
  • TAKAHASHI Motomichi
    Tokyo R&D Center, Miyarisan Pharmaceutical Co., Ltd. Department of Infectious Diseases, Kyorin University School of Medicine
  • KAMIYA Shigeru
    Department of Infectious Diseases, Kyorin University School of Medicine

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  • <i>Clostridium difficile</i>腸炎とプロバイオティクス

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Abstract

Clostridium difficile is a Gram-positive, obligately anaerobic, spore-forming bacillus which is the causative pathogen for pseudomembranous colitis (PMC), and it is associated with a large proportion of inpatient cases of antibiotic-associated diarrhea (AAD). Although C. difficile is known to be present in the normal intestinal microbiota, its growth is inhibited by other intestinal bacteria under normal conditions, and it is the disruption of intestinal microbiota by administration of antibiotics that allows C. difficile to overgrow and produce toxins (e.g., toxin A and toxin B) leading to C. difficile-associated diarrhea (CDAD). Withdrawal of antibiotics and/or administration of oral vancomycin or metronidazole are effective treatments for CDAD. However, recurrent cases are observed in 10 to 35% of CDAD and have become a difficult clinical problem. The main reservoirs of C. difficile are asymptomatic colonized persons and CDAD patients. C. difficile is transmitted through the fecal-oral route and can survive in a hospital environment for a long time in a spore form. It has been reported that the prevalence of C. difficile colonization is correlated to the duration of hospitalization. Some recurrent cases of CDAD are due to the same strain of C. difficile that caused the first episode persisting in the intestine after antibiotic treatment. Therefore, in the treatment and prevention of CDAD and/or recurrent CDAD, the prevention of a disruption of intestinal microbiota by the restriction of antibiotic use and the maintenance or restoration of normal microbiota colonizaiton are important, in addition to treatment with oral vancomycin/metronidazole and prevention through general contact precautions and environmental cleaning. Probiotics are used in the treatment and prevention of CDAD mainly as an adjunct to the antibiotic therapy for the purpose of maintaining or restoring the normal intestinal microbiota, and its efficacy has been reported by many researchers. From the viewpoint that probiotics have an inhibitory effect on the growth of pathogens and can restore the intestinal microbiota, they are seen as one of most theoretically suitable agents for the prevention of CDAD. However, their efficiencies are different across species or strains of probiotics and scientific evidence and proof based on large-scale clinical trials using each species or strain are desired.<br>

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