Clostridium difficile Infection: Prevention and Treatment

Authors and Disclosures

Tyler W. Barreto, MD, University of Texas Health San Antonio, San Antonio, Texas
Kenneth W. Lin, MD, MPH, Georgetown University, Washington, District of Columbia

Address correspondence to
Tyler W. Barreto, MD, at barreto@uthscsa.edu. Reprints are not available from the authors.

Author disclosure
No relevant financial affiliations.

Sidebar 1

Clinical Bottom Line

Summary of Key Findings and Strength of Evidence for Interventions to Prevent Clostridium difficile Infection

Intervention	Number of studies	Summary of key findings	Strength of evidence
Antibiotic stewardship	6	Appropriate prescribing practices were associated with decreased C. difficile infection.	⚫⚪⚪
Handwashing campaigns	1	Handwashing campaigns reduced C. difficile infection incidence (rates fell from 16.75 to 9.49 cases per 10,000 bed days).	⚫⚪⚪
Multicomponent prevention interventions*	4	Multicomponent interventions were sustainable over several years.	⚫⚪⚪

Strength of evidence scale
⚫⚫⚫ High: High confidence that the evidence reflects the true effect. Further research is very unlikely to change the confidence in the estimate of effect.
⚫⚫⚪ Moderate: Moderate confidence that the evidence reflects the true effect. Further research may change the confidence in the estimate of effect and may change the estimate.
⚫⚪⚪ Low: Low confidence that the evidence reflects the true effect. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
⚪⚪⚪ Insufficient: Evidence either is unavailable or does not permit a conclusion.
*—Multicomponent interventions consisted of using multiple prevention strategies to reduce C. difficile rates (e.g., the simultaneous use of education, isolation, handwashing, contact precautions, and environmental disinfection).

Sidebar 2

Clinical Bottom Line

Summary of Key Findings and Strength of Evidence for the Effectiveness of Fecal Microbiota Transplantation in Treating Recurrent and Relapsed Clostridium difficile Infection

Intervention studied	Outcome	Number of studies	Number of subjects	Summary of key findings	Strength of evidence
Fecal microbiota transplantation	Resolution of diarrhea and prevention of relapse	3 randomized controlled trials and 23 case series	751	Resolves diarrhea and prevents relapse in patients with recurrent C. difficile infection	⚫⚪⚪

Strength of evidence scale
⚫⚫⚫ High: High confidence that the evidence reflects the true effect. Further research is very unlikely to change the confidence in the estimate of effect.
⚫⚫⚪ Moderate: Moderate confidence that the evidence reflects the true effect. Further research may change the confidence in the estimate of effect and may change the estimate.
⚫⚪⚪ Low: Low confidence that the evidence reflects the true effect. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
⚪⚪⚪ Insufficient: Evidence either is unavailable or does not permit a conclusion.

Sidebar 3

Clinical Bottom Line

Summary of Key Findings and Strength of Evidence for the Effectiveness of Antimicrobials in Treating Initial Clostridium difficile Infections and Reducing Their Recurrence

Antimicrobial	Outcome	Number of studies	Number of subjects	Summary of key findings	Strength of evidence
Vancomycin vs. metronidazole	Initial cure of C. difficile infection	4	872	Favors vancomycin: 83.9% vs. 75.7% of patients achieved initial cure (RR = 1.08; 95% CI, 1.02 to 1.15)	⚫⚫⚫
Vancomycin vs. metronidazole	Prevention of C. difficile infection recurrence	4	705	No significant difference: 16.5% vs. 18.7% of patients had recurrent C. difficile infection (RR = 0.89; 95% CI, 0.65 to 1.23)	⚫⚫⚪
Fidaxomicin vs. vancomycin	Initial cure of C. difficile infection	2	1,111	No significant difference: 87.6% vs. 85.6% of patients achieved initial cure (RR = 1.02; 95% CI, 0.98 to 1.07)	⚫⚫⚪
Fidaxomicin vs. vancomycin	Prevention of C. difficile infection recurrence	2	962	Favors fidaxomicin: 14.1% vs. 26.1% of patients had recurrent C. difficile infection (RR = 0.55_; 95% CI, 0.42 to 0.71)*	⚫⚫⚫
Any antimicrobial	Treatment effect by disease severity	3	349 for initial cure; 91 for recurrence	Treatment results did not differ by disease severity	⚫⚪⚪

Strength of evidence scale
⚫⚫⚫ High: High confidence that the evidence reflects the true effect. Further research is very unlikely to change the confidence in the estimate of effect.
⚫⚫⚪ Moderate: Moderate confidence that the evidence reflects the true effect. Further research may change the confidence in the estimate of effect and may change the estimate.
⚫⚪⚪ Low: Low confidence that the evidence reflects the true effect. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
⚪⚪⚪ Insufficient: Evidence either is unavailable or does not permit a conclusion.
CI = confidence interval; RR = relative risk.
*—Limited evidence suggested that there was a lower rate of recurrence in patients receiving fidaxomicin when the infecting organism was a non-epidemic (non–nucleosome assembly protein 1) strain (˜¡¡).

Sidebar 4

Clinical Bottom Line

Summary of Key Findings and Strength of Evidence for the Effectiveness of Probiotics in Reducing Recurrence of Clostridium difficile Infection

Interventions compared (as an adjunct to standard antibiotic treatment)	Outcome	Number of studies	Number of subjects	Summary of key findings	Strength of evidence
Lactobacillus vs. placebo	Prevention of C. difficile infection recurrence	6	1,251	Favors Lactobacillus: RR = 0.27; 95% CI, 0.15 to 0.49	⚫⚪⚪
Saccharomyces boulardii vs. placebo	Prevention of C. difficile infection recurrence	6	1,244	No significant difference: RR = 0.77; 95% CI, 0.38 to 1.54	⚫⚪⚪
Multiorganism probiotics vs. placebo	Prevention of C. difficile infection recurrence	5	3,960	Favors multiorganism probiotics: RR = 0.50; 95% CI, 0.28 to 0.88	⚫⚪⚪

Strength of evidence scale
⚫⚫⚫ High: High confidence that the evidence reflects the true effect. Further research is very unlikely to change the confidence in the estimate of effect.
⚫⚫⚪ Moderate: Moderate confidence that the evidence reflects the true effect. Further research may change the confidence in the estimate of effect and may change the estimate.
⚫⚪⚪ Low: Low confidence that the evidence reflects the true effect. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
⚪⚪⚪ Insufficient: Evidence either is unavailable or does not permit a conclusion.
CI = confidence interval; RR = relative risk.