The Monthly Steward: Clostridium Difficile

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Each month, the Pharmacy team communicates a new focus. Last month focused on the Enterobacteriaceae family: Enterobacter, Proteus and Serratia. The February communication focuses on clostridium difficile.

Clostridium difficile (C. difficile) is a spore-forming, Gram-positive anaerobic bacillus. Clostridium Difficile Infection (CDI) makes up 15 to 25 percent of hospital-acquired antibiotic-associated diarrhea. CDI is the most severe form of antibiotic associated diarrhea and, untreated, can be fatal.

Risk factors for acquiring CDI include: advanced age, prolonged hospitalization, antibiotic exposure, chemotherapy, gastrointestinal surgery and acid suppressive therapy, with proton pump inhibitors.

Complications of severe C. difficile colitis include: dehydration, electrolyte disturbances, hypoalbuminemia, toxic megacolon, bowel perforation, hypotension, renal failure, systemic inflammatory response syndrome (SIRS), sepsis, and even death.

A diagnosis of CDI is based on a combination of clinical and laboratory findings. Most patients have both fever and leukocytosis. Diarrhea is almost universally present. Diarrhea is defined as at least three unformed stools per 24 hours. A diarrheal stool conforms to the shape of the container that holds it.  In addition, a stool laboratory test should return a positive result for the presence of  C. difficile  toxin.   There are four main types of stool tests that can be performed each with its pros and cons: Enzyme Immunoassay test (EIA); Polymerase Chain Reaction (PCR); Glutamate dehydrogenase combined with EIA test; and cell cytotoxicity assay. PCR is the most sensitive of all the tests. It will remain positive after resolution of C. difficile diarrhea. Therefore, a test of cure should not be performed.

The only time a form stool should be tested for the presence of C. difficile is if toxic megacolon is suspected as these patients will have an ileus. (Cohen et al., Infect Control Hosp Epidemiol 2010;31(5):431-455).

Once CDI is diagnosed, the first step is to stop the offending antibiotic if it all possible..  Antiperistaltic agents such Lomotil® should not be used as they tend to cause an ileus which causes retention of C. difficile toxins. Treatment is based on the severity of the infection and whether the patient is CDI naïve or not.  Intravenous or oral metronidazole is the antimicrobial of choice for an initial occurrence or mild to moderate infection. Oral vancomycin is used for severe cases and recurrent episodes.  Fecal levels of vancomycin administered at a dose of 125 mg by mouth every six hours exceed 100 times the amount required to kill the organism. Fidaxomicin is an agent that is mostly reserved for patients with more than one recurrent episode of CDI. Fidaxomicin is no more effective than vancomycin. Recurrence rates are lower with this drug but only in the non-epidemic strain of C. difficile. Fecal transplantation restores colonic flora and treats recurrent CDI as well. Fecal transplantation is the most effective therapy in patients who fail prolonged vancomycin papers.

C. difficile spores are ubiquitous in the environment. 3 to 5 percent of healthy people and up to 30 percent of hospitalized patients without diarrhea will test positive for the presence of C. difficile toxin. C. difficile colonization without diarrhea is not an indication for treatment and is not a disease. Patients with C. difficile diarrhea have extremely low levels of secretory IGA antibodies against the toxin. In essence, C. difficile diarrhea is a failure of the host to protect itself against the toxin

C. difficile is shed in feces and when surfaces are contaminated with fecal matter then they become reservoirs for C. difficile spores. Transmission is via the fecal-oral route.

Since transmission occurs so often in many healthcare settings, prevention efforts are necessary to aid in decreasing CDI occurrences.  Judicious antimicrobial usage (antibiotic stewardship) is of the utmost importance. Contact precautions and hand hygiene using soap and water are also necessary. Alcohol sanitizers do not effectively kill C. difficile spores. Adequate environmental cleaning and disinfecting procedures using bleach (sporicidal agent) to decontaminate C. difficile contaminated surfaces.

Thank you to Perpetuah Sherman, a pharmacist from our San Antonio facility, for her contributions to this month’s feature. If you are interested in contributing or have a specific topic you’d like to hear more about, contact VP of Ancillary Services Steven Harris or Director of Pharmacy Dru McLaughlin.

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