Dear Colleagues,

Clostridioides difficile was identified as the cause of pseudomembranous colitis, and much of antibiotic-associated diarrhea 40 years ago, and has become recognized as the leading single hospital-acquired infection in the United States, and probably worldwide.  In the last 15-20 years, there has been a surge in case-rates, complications and scientific inquiry of C. difficile.  These have translated into important changes in diagnostic and therapeutic paradigms which are discussed in this special issue.

The preferred diagnosis of C. difficile has evolved over time –from assays detecting the pathogenic C. difficile toxin proteins (e.g. cytotoxicity assays, immunoassays), to assays detecting the DNA of toxigenic strains by nucleic acid amplification (e.g. PCR), and now back to toxin detection.  While DNA assays are most sensitive, there is increasing recognition that toxin assays correlate best with severe disease and the need for treatment.  At the same time, newer more sensitive toxin assays approach the sensitivity of PCR; the clinical impact of these newer assays remains to be determined.  Finally, C.difficile culture has been considered impractical for clinical use, but remains invaluable for strain typing and epidemiologic studies.

The approach to treatment of C. difficile has also evolved in the past decade, with a new emphasis on 1. the goal of a sustained clinical response –i.e. clinical improvement without recurrence of diarrhea; and 2. the role of the “normal” intestinal microbiota (“good flora”) in preventing infection and relapse by C. difficile.  These considerations highlight the challenges of treating C difficile, whereby  relapse occurs typically in 20% of patients, with repeated recurrences in 5-10% of patients.  Thus, the most selective antimicrobials –active against C. difficile but sparing the normal flora, have demonstrated the greatest sustained clinical response.  Further, antibodies against C. difficile toxins facilitate clearance of the organism and decrease relapse.  Finally, restoring the “good microflora” by fecal microbiota transplant (FMT) has demonstrated unprecedented outcomes in the difficult population of frequent relapsers. While originally requiring colonoscopy to introduce “good” fecal microbiota, newer modalities such as fecal capsules are making this FMT methodology more acceptable, more available and increasingly considered in scenarios such as severe disease or even 1^st relapse.  Caveats to this methodology include the inconsistency and uncertainty of active components, potential for transmission of infectious agents and costs.

Two special scenarios present special therapeutic challenges. First, colonization by C. difficile without diarrheal disease may be protective against subsequent disease, or may be a precursor for clinical disease. The potential role of prophylactic treatment in this population is debated, while infection control measures seem to be effective.  At the other extreme, severe C. difficile disease is lacking in clear evidence-based interventions, though some antibiotic, FMT and surgical approaches seem to be effective.

Dr. Paul F. Riska
Guest Editor

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• Clostridioides difficile
• Diagnosis
• Treatment
• Antibiotic-associated diarrhea
• Fecal microbiota transplant