Dimitri M. Drekonja, MD, MS; Mary Butler, PhD, MBA; Roderick MacDonald, MS; Donna Bliss, PhD, RN; Gregory A. Filice, MD; Thomas S. Rector, PhD; Timothy J. Wilt, MD, MPH
Clostridium difficile infection is increasing in incidence and severity. The optimal treatment is unknown.
To determine whether, among adults with C. difficile infection, treatment with certain antibiotics compared with others results in differences in initial cure, recurrence, and harms.
MEDLINE, AMED, ClinicalTrials.gov, and Cochrane databases (search dates: inception through August 2011, limited to English-language reports); bibliography review.
Randomized, controlled trials of adults with C. difficile infection, independent of outcomes, who were treated with medications available in the United States. Observational studies reporting strain were included.
Study design, inclusion and exclusion criteria, quality and strength of evidence as assessed by 2 reviewers, study definitions, and duration of treatment and follow-up. Outcomes included initial cure, recurrence, and treatment harms.
11 trials that included 1463 participants were identified. Three trials compared metronidazole with vancomycin; 8 compared metronidazole or vancomycin with another agent, combined agents, or placebo. Strain was analyzed in 1 trial and 2 cohort studies. No study comparing 2 antimicrobial agents demonstrated a statistically significant difference for initial cure; all comparisons were of low to moderate strength of evidence. Moderate-strength evidence from 1 study demonstrated that recurrence was decreased with fidaxomicin versus vancomycin (15% vs. 25%; difference, −10 percentage points [95% CI, −17 to −3 percentage points]; P = 0.005). Subgroup analysis of a single study comparing metronidazole with vancomycin for patients who have severe C. difficile infection showed no difference by intention-to-treat analysis; this was rated as insufficient-strength evidence. Harms, when reported, did not differ between treatments in any study.
Definitions of diarrhea, C. difficile infection, initial cure, and relapse varied. Some studies reported insufficient detail to allow assessment of all randomly assigned participants or of harms.
No antimicrobial agent is clearly superior for the initial cure of C. difficile infection. Recurrence is less frequent with fidaxomicin than with vancomycin.
U.S. Department of Health and Human Services.
Several antibiotics are available for treatment of Clostridium difficile infections.
This comparative effectiveness review of 11 randomized trials involving adults with C. difficile found that initial cure rates did not statistically significantly differ for fidaxomicin, vancomycin, and metronidazole. Recurrent disease was common with all agents but was less frequent with fidaxomicin (15%) than with vancomycin (25%).
There were few studies, and most had small sample sizes. Studies used heterogeneous definitions for cure. Potential harms were inconsistently reported.
Any of several agents could be used for initial treatment of C. difficile infection. Fidaxomicin may be a superior agent for recurrent infection.
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Appendix Table 3.
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Martin H., Floch, Clinical Professor of Medicine
Yale University School of Medicine
December 30, 2011
Probiotics and fecal microbial transplants are treatments for Clostridium difficile infection
To the Editor:
Probiotics and fecal microbial transplants are treatments for Clostridium difficile infection.
In the December 20, 2011 issue of the Annals, the article entitled "Comparative Effectiveness of Clostridium difficile Treatments. A Systemic Review" as published by Drekonja and colleagues reports on a systemic review of antibiotic therapy but makes no mention of other treatments for recurrent and severe Clostridia difficile diarrhea infection. It is surprising that their discussion does not mention these treatments. Although there is controversy, the literature and studies in many institutions revealed that Saccharomyces boulardii and Lactobacillus GG have been reported repeatedly to be helpful in recurrent Clostridia difficile infection (1-3). Furthermore, the use of fecal microbial transplant (FMT) is now demonstrating surprising cures in patients with severe and resistant C. difficile infection. The review article published in the Annals leaves the reader with the impression that only antibiotics are treatments for this severe infection. Certainly, these other modalities of treatment, probiotics and FMT, are important and at times have been shown to be life-saving (4,5). They certainly should be mentioned at least in the discussion, and I would hope that the authors will correct the erroneous impression from this systemic review of antibiotics that only antibiotics are helpful in the treatment of Clostridia difficile.
1. Floch MH, Madsen KK, Jenkins DJA, et al. Recommendations for probiotic use. J Clin Gastroenterol 2006;40:275-278
2. Floch MH, Walker WA, Guandalini S, et al. Recommendations for probiotic use-2008. J Clin Gastroenterol 2008;42:S104-S108
3. Floch MH, Walker WA, Madsen K, et al. Recommendations for probiotic use -2011 Update. J Clin Gastroenterol 2011;45:S168-S171
4. Brandt L, Reddy SS. Fecal microbiota transplantation for recurrent Clostridium difficile infection. J Clin Gastroenterol 2001:45:S159-S167
5. Persky SE, Brandt LJ. Treatment of recurrent Clostridium difficile- associated diarrhea by administration of donated stool directly through a colonscope. Am J Gastroenterol 2000;95:3283-3295
Drekonja DM, Butler M, MacDonald R, Bliss D, Filice GA, Rector TS, et al. Comparative Effectiveness of Clostridium difficile Treatments: A Systematic Review. Ann Intern Med. ;155:839–847. doi: 10.7326/0003-4819-155-12-201112200-00007
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Published: Ann Intern Med. 2011;155(12):839-847.
Diarrhea, Gastroenterology/Hepatology, Healthcare Delivery and Policy, High Value Care, Infectious Disease.
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