Current and future treatment modalities for Clostridium difficile-associated disease

Current and future treatment modalities for Clostridium difficile-associated disease (CDAD) are reviewed. C. difficile, an anaerobic, spore-forming, gram-positive [corrected] rod, is the enteric pathogen most frequently identified in patients with antibiotic-associated, nosocomially acquired diarrhea. Infection can lead to severe gastrointestinal illness which can develop into pseudomembranous colitis. Recent outbreaks in North America involved more virulent C. difficile strains, more severe infections, and more complicated treatment courses. Because of the potential for increased toxin-associated damage due to increased toxin exposure time, CDAD treatment often involves cessation of the inciting antibiotic, C. difficile-targeted antibiotic therapy, electrolyte normalization, fluid replacement, and antimotility agent avoidance. First-line therapy for CDAD is treatment with the antibiotic metronidazole. Vancomycin is often used in more severe cases and for treatment-resistant organisms. Treatment regimens may also include probiotics, bile-acid sequestrants, and, in limited cases, intravenous immunoglobulin (IVIG). Alternative treatments for refractory and persistent CDAD include intracolonic vancomycin, nitazoxanide, rifaximin, IVIG, and probiotics. Several target proteins have been proposed for C. difficile vaccine production, including the flagellar cap protein FliD, flagellin FLiC, a cell wall protein (Cwp) (comprising amino- and carboxyl-terminal domains), a protease Cwp 84, and toxins A and B. Rarely, pseudomembranous colitis, a severe complication of CDAD, must be treated through surgical intervention. CDAD is a major concern for health care systems and clinicians. New diagnostic tests with increased sensitivity for detecting CDAD with a short turnaround time are necessary for early treatment and prevention. Continued research for more effective treatments and vaccine development for CDAD is also needed.