New guidelines offer help in diagnoses, treatment of C. difficile infection
Clostridium difficile infection is an increasingly common and severe infectious disease, with current health care costs of $3.2 billion annually. The diagnosis, treatment and management of patients with CDI also are complex, with variable disease severity and variable efficacy to therapy. The recently published guidelines from the American College of Gastroenterology provide evidence-based guidance for the diagnosis and treatment of CDI.
The diagnosis of CDI relies on detecting C. difficile toxin in stool. Although enzyme immunoassay (EIA) tests for toxin were widely used in the past, newer nucleic acid amplification tests (NAAT) such as PCR for toxin B are superior. Diarrheal stool from patients can be quickly and easily tested without the need for repeat testing; an early, simple, prompt diagnosis of CDI can lead to early, accurate treatment. Currently, following a patient’s clinical improvement is the most reliable way to assess resolution of CDI. Stool testing for cure should not be performed unless symptoms recur.
The severity of CDI has been difficult to standardize and to stratify. Previously, CDI was classified as mild, severe, or severe and complicated based on the presence or absence of a leukocytosis, a serum creatinine more than 1.5 times the premorbid level, hypotension, shock, ileus and megacolon. This classification was occasionally difficult to apply.
The recently published American College of Gastroenterology (ACG) guidelines help to simplify and standardize the recognition of CDI and its varying severities. Mild-to-moderate disease consists of diarrhea without any additional signs or symptoms of severe or complicated disease. Criteria for severe CDI consist of a serum albumin less than 3 g/dL and either a white blood cell (WBC) count of at least 15,000 cells/mm3 or abdominal tenderness, or both. Patients with complicated disease have any two of the following attributable to CDI: admission to the ICU, hypotension, vasopressors, fever of at least 38.5oC, ileus or significant abdominal distention, mental status changes, WBC count of at least 35,000 cells/mm3 or less than 2,000 cells/mm3, serum lactate levels of more than 2.2 mmol/L, and end organ failure. Recurrent CDI is return of diarrhea and documented C. difficile in the stools and can occur regardless of disease severity and despite appropriate initial therapy.
Guideline treatment recommendations have been tailored to the above disease classifications. For mild-to-moderate disease, metronidazole 500 mg orally three times a day for 10 days remains the initial recommended therapy. If metronidazole is contraindicated or cannot be tolerated, vancomycin 125 mg orally four times a day for 10 days can be used. Additionally, if no improvement is noted after 5 to 7 days of therapy with metronidazole, the recommendation is to change to the above vancomycin regimen.
For severe disease, vancomycin 125 mg orally four times a day for 10 days is recommended therapy. For complicated disease, vancomycin 500 mg orally four times a day and metronidazole 500 mg IV every 8 hours is recommended therapy and the addition of vancomycin per rectum (500 mg of vancomycin in 500 mL of saline as an enema) can be considered, especially if the patient’s course is complicated by an ileus.
Image: CDC/Jones G
Recurrent disease can be treated by repeat metronidazole or a vancomycin pulse regimen. Fecal microbiota transplant can be considered after three recurrences of CDI.
Besides these treatments, careful assessment of all patients is necessary to ensure appropriate therapy. Abdominal CT scanning should be utilized in patients with complicated disease. Surgical consultation is recommended for all patients with hypotension who require vasopressor therapy, sepsis and organ dysfunction, mental status changes, failure to improve, a WBC count of at least 35,000 cells/mm3, a serum lactate at least 5 mmol/L, or failure to improve on appropriate antibiotic therapy.
Prevention remains the best ultimate treatment for all patients. Antibiotic use and pathogen exposure remain the two greatest risks factors for acquiring CDI. All practitioners caring for patients with or at risk for CDI should focus on careful antibiotic stewardship and hand hygiene. Hospitals should consider infection control programs focused on decreasing the incidence of CDI. Patients with known or suspected CDI should be placed under contact precautions until, at a minimum, their diarrhea has resolved.
CDI has become increasingly common in the past decade. Newer diagnostic tests such as PCR for toxin B have improved diagnostic accuracy and can lead to early therapy and isolation measures to prevent nosocomial spread. Disease classification into mild, moderate, severe or recurrent disease is important for tailoring and starting appropriate therapy. Prevention remains the best — and safest — treatment available to patients. Practitioners should focus on careful antibiotic stewardship and hand hygiene.
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Christina M. Surawicz, MD, is Chief of Gastroenterology, Harborview Medical Center and Professor of Medicine, University of Washington School of Medicine, Seattle, as well as Assistant Dean for Faculty Development.
Disclosure: Owens and Surawicz report no relevant financial disclosures.