Therapeutic Approaches for Clostridium difficile Infections

Abstract

Metronidazole and vancomycin remain the front‐line therapies for most Clostridium difficile infections (CDI). However, recurrent CDI occurs in ∼25% of patients, causing significant morbidity and mortality and healthcare costs. For this population, traditional antibiotic therapies fail and new treatment options are greatly needed. The US Food and Drug Administration recently approved fidaxomicin for CDI treatment. This narrow‐spectrum antibiotic preserves the normal gut microbiota and shows promise as a treatment for severe and recurrent CDI. Monoclonal antibodies and vaccines directed against toxin are currently in clinical trials and represent alternative, non‐antibiotic therapies. Less traditional therapeutic interventions include bacteriotherapy with non‐toxigenic C. difficile and fecal transplant. This commentary will provide an overview of current and forthcoming CDI therapies. Curr. Protoc. Microbiol. 30:9A.3.1‐9A.3.9. © 2013 by John Wiley & Sons, Inc.

Recurrent Clostridium difficile infection: From colonization to cure

“…For over 30 years vancomycin and metronidazole have been the cornerstones of CDI treatment. Vancomycin is a poorly-absorbed oral glycopeptide antibiotic that attains high concentrations in the large intestine and that works by interfering with gram-positive bacteria cell wall synthesis 106 . Metronidazole is a bactericidal nitroimidazole antibiotic with selective anaerobic activity that prevents DNA replication 107 .…”

“…A potential explanation of these observations is that vancomycin is significantly more effective than metronidazole at inducing bacteriologic cure among RCDI patients 22 . Even so, the apparent clinical benefit of vancomycin may be offset by its high cost and deleterious effects on commensal gram-positive gut microflora (which may, notably, contribute to further recurrence) 106 and concerns about VRE resistance 115 . The significance of such concerns will remain ambiguous without further randomized controlled trials.…”

Dietary flaxseed intake exacerbates acute colonic mucosal injury and inflammation induced by dextran sodium sulfate

“…IL-6, IL-1β and TNF-α) (72, 99) and various extra-intestinal manifestations, including hepatic disorders (94). While some of the most common non-surgical treatments for colitis-associated diseases include anti-inflammatory agents, immunosuppressants, and antibiotics, patients often suffer from severe side effects, fail to respond, or become resistant to such therapies (23,38,60). Therefore, alternative or complementary therapies, including prebiotics, probiotics, and butyrate (29,33,65,96,98), phenolic compounds (e.g.…”

Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT

“…The standard therapy for C. difficile infection is treatment with metronidazole, vancomycin, or fidaxomicin. 90% of all treated patients respond to this therapy, but of these patients 15–30% suffer from relapsing infection 3 6 47 . Therefore, there is a need for the development of alternative therapeutic options to treat C. difficile infections 48 .…”