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Infection: A Clinical Review

    Clostridium Difficile 
Infection: A Clinical Review

    Clostridium Difficile Clinical Pearls

    Clostridium difficile is a gram positive, spore and toxin producing, anaerobic bacillus that is a very common and clinically important; it is a cause of acute diarrhea in long term care facilities such as nursing homes, hospitals, and personal care homes.

    Due to the possibility of fulminant colitis, leading to perforation and death, as well as the transmissibility of the disease, early detection and prevention is crucial.

    The disease is on a spectrum, as patients can be asymptomatic carriers or develop a rapidly progressive colitis, that can be life threatening.

    Transmission of Clostridium Difficile

    Infection control has limited the spread of C. diff in hospitals, but it remains very transmissible. Along with MRSA, C. Diff infection is one of the most common hospital acquired infections and causes up to 25% of antibiotic associated diarrhea (Brown and Rodi, 2016).

    C. diff exists in vegetative spores that unfortunately are able to lay dormant on surfaces for months.

    The disease itself is spread through the fecal oral route. In a susceptible host, there must be contamination, via the above route accompanied by an alteration in the normal fecal microbiota. (usually due to recent antibiotic use).

    C-Diff Risk Factors

    When the toxins produced by C. diff are released, it causes an alteration in the colonic mucosa which results in inflammation of the colon.

    The most common risk factor for an episode of C. diff infection is recent antibiotic use. Many antibiotics are implicated, but clindamycin is notorious. This is also frequently tested.

    Other considerations include fluoroquinolones, penicillin, and cephalosporins, respectively.

    Additional risk factors include age greater than 65, recent hospitalization or exposure to health care facilities, and long term use of proton pump inhibitors.

    Specifically, with antibiotic therapy, the infection may begin during antibiotic use or after cessation. According to some sources, up to 10 weeks after cessation, symptoms can still be manifested. This is important to recall, as patients may need reminders regarding antibiotics prescribed greater than two months prior.

    Patient History

    Patient history is important to characterize risk factors for infection. The classic patient may present with a history of hospitalization, antibiotic use, old age, and chronic PPI use, but the disease can be subtle as well.

    Classically, patients will have greater than 3 watery, poorly formed stools in greater than 24 hours. Diarrhea may be entirely watery, or may contain blood.

    Patients may complain of abdominal pain or abdominal cramping. Pain may be mild or severe. Patients may complain of nausea, vomiting, fever, chills, and anorexia.

    The Physical Exam

    The exam in a patient with C. Diff is variable. Patients with mild disease may have a fairly normal exam. Patients may have significant abdominal tenderness. Fever, tachycardia, unstable vital signs, rebound tenderness or guarding should raise concern for bowel perforation.

    Diagnosing Clostridium Difficile

    Once the diagnosis is suspected, lab work is a good first step. A CBC can be supportive of the diagnosis. A white blood cell count less than 15,000 is suggestive of mild disease, while more severe disease can have a white blood cell count greater than 30,000.

    A rise in serum creatinine can be seen as well as elevated inflammatory markers.

    The mainstay of diagnosis however, is testing for Clostridium difficile toxins. A stool sample is necessary for evaluation. It is important to note that the stool sample must be almost entirely liquid for analysis.

    Additionally, the sample must be frozen immediately once given or be analyzed within 1-2 hours of defecation. During transport to the lab for analysis the sample should be kept at 4 degrees Centigrade.

    Depending on laboratory preference, the enzyme linked immunoassay or polymerase chain reaction may be used. The ELISA is commonly available, fairly inexpensive and rapidly available.

    The most sensitive test is a stool culture. A positive toxin result in the setting of diarrhea is considered positive.

    Patients without diarrhea should not be tested for Clostridium difficile.

    In the emergent setting, patients may need imaging or procedural diagnosis. A CT scan may indicate colitis or demonstrate thickening of the colon wall.

    Patients undergoing colonoscopy may show the classic “pseudomembranous colitis” which is pathognomonic for the disease.

    An x-ray can be ordered quickly in the emergent setting to rule out intestinal obstruction, perforation, or ileus.

    Treating Clostridium Difficile

    Once the diagnosis is confirmed, treatment should not be delayed. Many patients can be managed in the outpatient setting as long as they are stable. Patients with signs of shock, hemodynamic instability or surgical abdomens should certainly be referred to the emergency department for evaluation.

    The first line outpatient treatment is metronidazole 500 MG PO QID for 10 to 14 days. Patients intolerant to metronidazole can be treated with vancomycin 125 mg PO QID for 10 to 14 days.

    Patients with hypovolemia, hematochezia, inability to tolerate PO intake should be referred for admission. Patients with signs of instability may need IV antibiotics.

    Fidaxomicin is another option, but may not be readily available.

    C-Diff Recurrence

    Unfortunately, recurrence is common with this disease. Up to 25% of patients may have recurrent disease within the first 30 days after treatment. Guidelines suggest that at the onset of the first recurrence, the same antibiotic can be used.

    For a second recurrence, a pulse dose of vancomycin may be useful.

    The absolute last resort, related to treatment, is a fecal transplant which has a very high overall cure rate. Once a donor is identified, a fecal transplant via  colonoscopy can be performed.

    The hallmark of management of Clostridium difficile is also prevention of spread. About 20% of patients in long term care facilities are asymptomatic carriers which can unknowingly cause spread. As discussed previously, spores can lay dormant for long periods of time on surfaces.

    Judicious use of antibiotics is extremely important. Being that most cases are caused by antibiotic use, avoiding unnecessary use is paramount.

    Clostridium Difficile Clinical Pearls

    Another important pearl is that C. diff spores can be resistant to alcohol based gels, so using hand sanitizer is not sufficient.

    Patients, health care professionals, and others should be encouraged to use soap and water to prevent spread.

    Chronic proton pump inhibitor use should be discouraged when applicable.

    Patients with documented infection, should be counseled on proper hand washing techniques. Patient rooms should be outfitted with gowns, gloves and providers should be encouraged to thoroughly wash their hands between each patient.

    Patients should be educated that they may shed spores up to 6 weeks after being successfully treated for the disease.

    Clostridium difficile infection is a clinically relevant, commonly tested medical condition. Clinicians should consider the diagnosis in any patient with recent antibiotic use or diarrhea.

    Prompt recognition and treatment of the disease along with education about prevention measures can greatly reduce the morbidity and mortality associated with the disease.

    Brown, S.L. and Rodi, S.W. (2016). Clostridium Difficile Infection. The Five Minute Clinical Consult.


    McDonald, C and Kutty, P (2017). Clostridium Difficile Infection: Prevention and Control. UpToDate. Date of Access: 26 December 2017.

    This blog or podcast should not be used in any legal capacity whatsoever, including but not limited to establishing standard of care in a legal sense or as a basis for expert witness testimony. No guarantee is given regarding the accuracy of any statements or opinions made on the podcast or blog.

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    Daniel Champigny, PA-C is a 2016 graduate of The Pennsylvania State University. Prior to attending PA school, Dan worked in pre-hospital medicine as an EMT. Currently, he's in primary care/family medicine in rural Pennsylvania and also works in urgent care. He is a certified impact consultant and is passionate about the management and treatment of concussions. Dan additionally has interests in preventive care, evidence based medicine, and teaching. In his spare time, Dan enjoys running and hiking.