Dx, Prevention, and Rx of C. difficile – Help and Resources From AHRQ

All the resources in this post are from the Agency For Health Care Research and Quality.

What follows are excerpts from Resource (1):

Focus of This Summary

This is a summary of a systematic review that evaluated the recent evidence regarding the accuracy of diagnostic tests and the effectiveness of interventions for preventing and treating Clostridium difficile (C. difficile) infection. The systematic review included 93 articles published between 2010 and April 2015. This summary is provided to assist in informed clinical decisionmaking. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.


C. difficile is a Gram-positive, anaerobic, spore-forming bacterium generally acquired through ingestion. Symptoms of C. difficile infection (CDI) can range from mild diarrhea to severe conditions such as pseudomembranous colitis and toxic megacolon that can result in death. The estimated mortality rate for health care-associated CDI ranged from 2.4 to 8.9 deaths per 100,000 in 2011. For people ≥65 years of age, the mortality rate was 55.1 deaths per 100,000.

Effective containment and treatment of CDI depends on accurate and swift diagnosis. CDI is diagnosed using clinical findings and tests such as: (1) nucleic acid amplification using loop-mediated isothermal amplification (LAMP) and the polymerase chain reaction (PCR), (2) tests for disease- generating C. difficile toxins (including immunoassays), and (3) test algorithms (these are two-step procedures: the first step is a fast screen for the presence of the organism using a test such as the glutamate dehydrogenase [GDH] assay; if the first test is positive, a second test for toxins is performed).

Efforts to prevent CDI include antimicrobial stewardship, the use of infection-control strategies such as handwashing, and immune-boosting strategies. Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials to reduce microbial resistance and decrease the spread of infections. Handwashing with soap and water is helpful for removing C. difficile spores, which are resistant to alcohol rubs or hand sanitizer. Measures that improve a patient’s immune defenses include the use of probiotics to promote healthy gut flora and the maintenance of balanced nutrition.

Initial treatment of CDI commonly involves the use of oral antimicrobials such as metronidazole and vancomycin. Mild to moderate initial CDI is often treated with metronidazole, while severe initial CDI is often treated with vancomycin. Treatment with metronidazole and vancomycin can be problematic, however, as they have been implicated in the development of vancomycin-resistant enterococci in immunocompromised patients.

CDI recurs in 15 to 35 percent of patients who have had one previous episode and in 33 to 65 percent of patients who have had more than two previous episodes. Diagnosis and treatment of relapsed or recurrent CDI are challenging. Diagnosis of recurrent CDI is based on the recurrence of clinical symptoms, and repeat testing may not be required. Currently, clinicians choose from a variety of antimicrobials, dosing protocols, and adjunctive treatments (such as probiotics and fecal microbiota transplantation [FMT]) to manage relapsed or recurrent CDI.

The current review aimed to update a 2011 review regarding the accuracy of CDI diagnostic tests and the effects of interventions to prevent and treat CDI in adults.


Diagnosis of CDI: Nucleic acid amplification tests have high sensitivity and specificity for diagnosing CDI (high strength of evidence [SOE]). (See Table 1.)

Prevention of CDI: Strategies such as antibiotic stewardship and handwashing campaigns may help prevent CDI (low SOE). Further evidence is needed to confirm that prevention strategies impact patient outcomes such as CDI incidence. (See Table 2.)

Treatment of CDI: Vancomycin is more effective than metronidazole for the initial treatment of CDI (high SOE), while fidaxomicin is more effective than vancomycin for the prevention of recurrent CDI (high SOE). Physicians may take into consideration disease and patient characteristics, effectiveness, potential adverse effects, patient preferences, and costs when choosing an antibiotic to treat CDI. Lactobacillus probiotics, when used as an adjunct to antibiotic therapy, may prevent the recurrence of CDI (low SOE); additionally, probiotics are generally safe in otherwise healthy patients. There is low SOE that FMT may be effective for treating recurrent and relapsed CDI; however, there is consistent positive evidence for its effectiveness in patients with recurrent and relapsed CDI. (See Tables 3, 4, and 5.)


(1) Diagnosis, Prevention, and Treatment of C. difficile: Current State of the Evidence – Clinician Summary – May 30, 2017 from Effective Health Care Program of the Agency For Health Care Research and Quality
(2) Treating and Preventing C. difficile Infections: A Review of the Research for Adults – Consumer Summary – May 30, 2017 from Effective Health Care Program of the Agency For Health Care Research and Quality.

(3) Early Diagnosis, Prevention, and Treatment of Clostridium difficile: Update – Comparative Effectiveness Review Number 172. AHRQ Publication No. 16-EHC012-EF March 2016 [Full Text PDF] 136 pages.

(4) Treating and Preventing C. difficile Infections: A Review of the Research for Adults [PDF]

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