REVIEW QUESTION

What is the efficacy and safety of antibiotic treatment for Clostridium difficile infection (CDI) in adults?

TYPE OF REVIEW

This is a systematic review of 22 studies, including a total of 3,215 participants.

RELEVANCE FOR NURSING

While C. difficile is not normal bowel bacteria in adults, it can live in the human intestine without causing problems. However, in certain circumstances these bacteria can overgrow, destroying the normal gut flora and secreting toxins that cause diarrhea. CDI often results from the use of oral, parenteral, or topical antibiotics, and can be fatal. Treatment involves discontinuing the antibiotic and starting an antibiotic effective against C. difficile, allowing normal bowel flora to regenerate. CDI is the leading cause of gastrointestinal-related death in the United States, and CDI morbidity and mortality rates have been rising over the past decade. This rise correlates with the recent identification of a new, highly virulent, and multidrug-resistant variant of C. difficile: ribotype 027.

CHARACTERISTICS OF THE EVIDENCE

This review examined the efficacy and safety of antibiotic treatment for CDI. Twenty-two studies with a total of 3,215 participants were included. Participants were 18 years of age or older who had diarrhea, had a positive stool culture for CDI, and were using antibiotics for an infection other than C. difficile. The studies compared antibiotics, the timing or doses of the same antibiotic, or antibiotic therapy versus placebo for the treatment of CDI.

The primary outcomes were sustained symptomatic or bacterial cure with no recurrence of diarrhea due to CDI, death for any reason, drug-related adverse effects from the antibiotics, and cost of the antibiotics. Most studies compared vancomycin to other antibiotics, including metronidazole, teicoplanin, and fidaxomicin, among others. Only one study compared vancomycin to placebo.

In achieving a symptomatic cure (defined as resolution of diarrhea and no CDI recurrence), fidaxomicin was more effective (and teicoplanin possibly more effective) than vancomycin, which was more effective than metronidazole. A total of 140 deaths were reported across all studies, but all were attributed to preexisting conditions and not to CDI. It was not possible to analyze drug-related adverse events as they were reported differently in each study. They included pruritus, joint pain, nausea, vomiting, and elevation of liver enzymes. Metronidazole was the least expensive antibiotic and vancomycin cost less than fidaxomicin and teicoplanin.

BEST PRACTICE RECOMMENDATIONS

There is a lack of evidence to recommend the use of antibiotics in patients with mild CDI or when to stop the causative antibiotic and start the new therapy. Most studies in this review excluded participants with severe CDI. Moderate-quality evidence indicated that in mild CDI, fidaxomicin is more effective than vancomycin, which is more effective than metronidazole. However, the differences in efficacy between these three drugs were not great and metronidazole cost much less than the other two.

RESEARCH RECOMMENDATIONS

Adequately powered, randomized, placebo-controlled trials are needed to assess the cessation of the initial antibiotic and the timing and duration of CDI therapy. The quality of evidence regarding teicoplanin was very low and more research is needed to establish its efficacy. The increasing severity of C. difficile also highlights the need to investigate antibiotic treatment in severely ill patients with CDI. Other issues include the treatment of recurrent symptoms, the use of IV compared with oral antibiotics, and antibiotic resistance.

REFERENCE