New antimicrobial agents for patients with Clostridium difficile infections

Current drug treatment of Clostridium difficile infection (CDI) focuses on metronidazole and vancomycin. Early studies showed equivalence, but more recent reports indicate that oral vancomycin is preferred for serious CDI. Recent work has demonstrated a need for new drugs due to challenges with the NAP-1 strain, which appears to cause more refractory disease that is more likely to relapse. These two distinctive facets of treatment are the most challenging. This review discusses new agents in development: antibiotics, probiotics, immune response products, and agents to bind C. difficile toxins. None are likely to be more effective than oral vancomycin for acute infection. However, several may be as effective, without causing relapse or promoting unnecessary antibiotic use for multiple conditions. The greatest promise is with agents used to interrupt relapses. In this category the leading new agents appear to be antibiotics (rifaximin, nitazoxanide, difimicin, ramoplanin), toxin-binding agents (tolevamer), probiotics (Saccharomyces -boulardii and Lactobacillus ramosus), and immune agents (toxoid vaccine and hyperimmune globulin). The drugs that appear most promising based on recent trials are rifaximin, tolevamer, and difimicin, which appear promising for reducing relapses.