February 03, 2015
Diagnosis and Treatment of Clostridium difficile in Adults
JAMA : The Journal of the American Medical Association
TAKE-HOME MESSAGE
- In this systematic review, 116 articles were analyzed to determine the best practices for Clostridium difficile (CDI) diagnosis and treatment in adults.
- Although C. difficile diagnostic testing is sometimes complex, several treatment options are available, including antibiotics and fecal microbiota transplantation.
Written by David Rakel MD, FAAFP
C. Difficile Update: Diagnosis and Treatment
The incidence of C. difficile (difficult to treat) has doubled from 2001 to 2010. This is likely related to an aging population and the overuse of antibiotics and proton pump inhibitors. Other risk factors include chemotherapy, hospitalization, use of feeding tubes, and chronic kidney disease.
This summary of 116 articles gives us a nice update in treating this growing pathogen. One of the key pearls from this paper is don’t test asymptomatic people. About 10% to 52% are asymptomatic carriers (the percentage is higher in kids), and testing may result in overtreatment. Testing is only indicated for those who are symptomatic with three or more watery stools in 24 hours.
The second most important pearl related to the first is that the disease is related to the c. diff toxin, not the bug. There are many strains of C. difficile that don’t produce the toxin. It is the toxin that harms the enteral lining, which results in inflammation that creates a pseudo-membrane of inflammatory neutrophils.
Lab testing cannot tell the difference between colonization and infection. After treatment, spores can shed for 6 weeks so don’t test for a cure as testing can continue to be positive. This can result in unnecessary treatment. Don’t retest unless the patient continues to have three or more watery stools per day.
To prevent a recurrence, stop antibiotics and proton pump inhibitors when able. The antibiotics with the greatest risk of associated c. diff colitis include penicillin, cephalosporin, and clindamycin. Using probiotics and fermented foods such as kefir have also shown benefit in preventing a recurrence by improving the balance of the microbiome, which is negatively influenced by disease, age, drugs, and poor nutrition.
Abstract
IMPORTANCE
Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased.
OBJECTIVE
To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥18 years).
EVIDENCE REVIEW
Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process.
FINDINGS
Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases ofCDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI).
CONCLUSIONS AND RELEVANCE
Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient’s risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.