Clostridium difficile infection (CDI) is a global public health problem. In the United States alone, C difficile causes approximately 500,000 infections and 29,000 deaths annually.1 The rise in CDI-related morbidity and mortality over the past 2 decades is multifactorial but partly associated with emergence and global dissemination of potentially hypervirulent, antibiotic-resistant strains of C difficile.2 This rise in severe and fulminant CDI has led to an increase in the number of patients requiring an intensive care unit (ICU) admission for severe colitis. In addition, patients in the ICU for other conditions are also at risk of developing non-severe CDI related to underlying comorbidities (eg, elderly, prolonged length of stay, enteral feeds, immunosuppression) and medication exposures (eg, antibiotics and proton pump inhibitors). It is estimated that approximately 1% to 2% of adults in the ICU develop CDI.3
If CDI is diagnosed in the ICU, it is extremely important to determine whether CDI is the cause of critical illness because this impacts management decisions. Various infectious diseases and gastroenterology societies have proposed criteria for distinguishing nonsevere (also referred to as mild/moderate), severe, and fulminant (also referred to as severe, complicated) CDI,3 although these definitions have not been clinically validated. Of note, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) have recently published updated CDI management guidelines. In general, severe CDI is associated with leukocytosis, acute kidney injury, and/or possibly hypoalbuminemia.3,4 Fulminant CDI is associated with hypotension, shock, ileus, and/or toxic megacolon.3,4 This condition can potentially lead to colectomy and/or death. Of note, the above CDI severity criteria function particularly poorly in pediatric patients.
CDI diagnosis continues to be a challenge and was a major focus of the recently published IDSA/SHEA CDI guideline.4 This is because unlike tests that detect free toxin in stool (eg, toxin enzyme immunoassay), nucleic acid amplification tests (NAATs), the most commonly used test for CDI in the United States, do not differentiate between colonization and infection. Because approximately 20% of hospitalized patients are colonized with C difficile, differentiating diarrhea caused by C difficile from an alternate etiology in a patient with C difficile colonization can be difficult. This is especially true in the ICU where 15% to 40% of patients develop diarrhea.3 Thus, it is extremely important to practice good diagnostic stewardship and limit C difficile testing to patients with high pretest probability of CDI: new-onset, unexplained, and clinically significant (ie, at least 3 unformed stools in a 24-hour period) diarrhea. Furthermore, testing should be avoided in patients with other probable causes of diarrhea, such as diarrhea concomitant with initiation of enteral feeds or laxatives. In the pediatric ICU, occasionally a positive NAAT for C difficile may delay the recognition of other serious diagnoses that present with gastrointestinal symptoms, such as toxic shock syndrome or neutropenic enterocolitis (ie, typhlitis). Thus, it is important to maintain a broad differential diagnosis in critically ill patients with gastrointestinal symptoms irrespective of their C difficile test result because patients may require empiric treatment for both conditions.
Treatment of patients with CDI in the ICU varies depending on the severity of their gastrointestinal illness. The recent updated IDSA/SHEA guideline4 now recommends vancomycin (125 mg QID) or fidaxomicin (200 mg BID) alone for nonsevere or severe CDI in adults. Thus, metronidazole is no longer recommended for treatment of nonsevere or severe CDI in adults. In patients with fulminant CDI, high dose vancomycin (500 mg QID) given orally or per rectum (if ileus is present) is recommended. In this case, intravenous metronidazole can be used adjunctively. In severely ill patients, urgent surgical consultation should be obtained. Surgical options to be considered include subtotal colectomy (with preservation of rectum) or diverting loop ileostomy.
While the efficacy of fecal microbiota transplantation (FMT) for recurrent CDI has been well described, the use of FMT for severe CDI is controversial and not currently recommended.4 However, a recent retrospective study of FMT given early in the course of severe CDI showed promising results. In this study of 111 patients in France, early FMT significantly improved survival in patients with severe CDI (odds ratio 0.08, P =.001) but not patients with nonsevere CDI (odds ratio 1.07, P =.97).5 As experience with FMT for severe CDI expands, FMT may ultimately emerge as a recommended treatment modality.
Prevention of CDI remains a vitally important strategy for improving the care of patients in the ICU.4 To prevent transmission in the ICU, patients with CDI should be placed in contact isolation, and healthcare workers should don gloves and gowns and perform hand hygiene when caring for those patients. Disposable and/or dedicated medical equipment should be used in the care of patients with CDI when feasible. In all patients, avoiding unnecessary antibiotics and proton pump inhibitors may reduce the risk for CDI. While some studies have suggested that probiotics may be effective for primary CDI prevention, these data are relatively weak and probiotics are not currently universally recommended in primary CDI prevention.
In summary, CDI is a relatively common ailment in patients in the ICU setting. It is important to understand the relative severity of CDI in patients in the ICU because it effects treatment decisions. However, primary prevention remains a vitally important strategy to limit morbidity and mortality related to CDI in this vulnerable patient population.
- Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372:825-834.
- Kelly CP, Lamont JT. Clostridium difficile—more difficult than ever. N Engl J Med. 2008;359(18):1932-1940.
- Prechter F, Katzer K, Bauer M, Stallmach A. Sleeping with the enemy: Clostridium difficile infection in the intensive care unit. Crit Care. 2017;21:260.
- McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66:987-994.
- Hocquart M, Lagier JC, Cassir N, et al. 2018. Early fecal microbiota transplantation improves survival in severe Clostridium difficile infections. Clin Infect Dis. 2018;66:645-650.