Clostridium difficile infection (CDI) is a common and costly bacterial illness in hospitalized patients, involving 1% of U.S. hospital stays with an aggregate cost of $8.2 billion annually.1 The spore-forming, gram-positive bacillus is spread by the fecal-oral route; in health-care settings, it is often transmitted by hand carriage and contamination of environmental surfaces. C. diff produces toxins that can cause a spectrum of diseases, including asymptomatic carriage, mild to severe diarrhea, colitis, and pseudomembranous colitis, which in severe cases can lead to sepsis, colectomy, or death.
CDI is defined as the acute onset of diarrhea in a patient with documented toxigenic C. diff or C. diff toxin, without any other clear cause of diarrhea.2 In the past decade, CDI has increased in frequency and severity, with most experts thinking it is related to a particularly virulent strain known as BI/NAP1/027.3 Antibiotic exposure is the most significant and modifiable risk factor for CDI, with increasing age, gastric acid suppression, and immunocompromised states also placing patients at increased risk for developing infection.
In February, the American College of Gastroenterology (ACG) released guidelines for diagnostic testing and pharmacologic therapy for CDI, management of complicated and recurrent disease, and infection control and prevention.2 Previous recommendations for the prevention, diagnosis, and treatment of CDI have been provided by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and a collaboration of the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).4,5 Recommendations addressing CDI in infants and children are also available.6 The 2013 ACG guidelines are the first from this group to address CDI and are intended to supplement previously published guidelines.
Diagnostic testing. The ACG guidelines emphasize that only stools from patients with diarrhea be tested for C. diff and/or its toxin. Colonization with C. diff is common, and performing tests in asymptomatic patients may complicate clinical care. Rarely, patients with CDI will develop ileus, and in those cases, rectal swab may be performed, but in nearly all circumstances, only diarrheal stools warrant testing. The authors also strongly discourage repeat testing after a negative test and testing for cure following treatment and resolution of symptoms. All of these recommendations are consistent with the SHEA-IDSA guidelines and reflect moderate- to high-quality evidence.
Recognizing that diagnostic testing for C. diff continues to evolve, the ACG makes specific recommendations regarding the use of newer tests, such as nucleic acid amplification and glutamate dehydrogenase detection. These are favored over toxin A and B enzyme immunoassay testing due to higher sensitivity.
Management of mild, moderate, and severe CDI. As with prior guidelines, the 2013 ACG guidelines stratify treatment recommendations by disease severity. Mild to moderate disease, which includes diarrhea only (mild) or diarrhea with signs and symptoms not meeting criteria for severe or complicated CDI (moderate), should be treated with metronidazole 500 mg orally three times daily for 10 days. Oral vancomycin should only be used in patients with mild to moderate disease who fail to respond after five to seven days of metronidazole or in those who are intolerant to metronidazole, or pregnant or breastfeeding. Although fidaxomicin is FDA-approved to treat mild to moderate CDI, the ACG does not make a formal recommendation on its use, given its high cost and limited data to support its effectiveness.
The ACG defines severe disease as CDI in patients with albumin <3 g/dL, and either WBC ≥15,000 cells/mm3 or abdominal tenderness. Though this definition of severe disease differs from the ESCMID and SHEA-IDSA definitions, which include elevated creatinine (>50% greater than premorbid level) instead of low albumin, the treatment recommendation is the same: vancomycin 125 mg orally four times daily for 10 days. While vancomycin and metronidazole are equally effective in mild to moderate CDI, there is some evidence to suggest that vancomycin is more effective in severe disease.7