Oct 23, 2020
This podcast presents, Dr. Elliot Francke, an infectious disease specialist with Midwest Infectious Disease Consultants, who provides an update on clostridioides difficile (C.Diff).
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In 1983, a pseudomembranous colitis was identified. In 1935, the organism was isolated. In 1978, Clostridium Difficile was identified as an organism that produces toxins causing diarrhea. In the last year, the genius has been renamed and the organism is now known as Clostridioides Difficile.
The organism produces two toxins A and B. A is an immunogenic toxin that causes an influx of immune cells and some cell necrosis. Toxin S can be eliminated with a monoclonal antibody but does not stop the disease. Toxin B is of greater concern and causes cell death and pseudomembrane buildup in the large bowel lining. Bezlotoxumab is discussed again later, but is a commercial antibody that does not eliminate the disease but decreases the severity of it.
Prevalence in the adult population is around 3-5%. For those over 60, prevalence is 50%. There are a large percentage of individuals who are colonized but not producing the toxin, otherwise known as non-toxigenic C. DIff.
C. Diff organisms are difficult to combat for several reasons. The organism is a gram positive rod, that does not have the attachment points for some standard antibiotics. It also has that ability to efflux antibiotics out of the cell. When attacked, it can produce spores that are impenetrable by both the immune system and many antibiotics, and can live for long periods of time on surfaces waiting for the right opportunity. Creepy microbes. Growth in the bowel can be inhibited by 14-16 natural flora identified in two Canadian studies.
Those at greater risk for C. Diff infections are over the age 65, in long-term hospitals or institutions, immunosuppressed, or chronic PPIs, or have had recent use of certain systemic antibiotics. The correlation to antibiotics was discovered in 1978, and originally linked to clindamycin. Currently use of 3rd or 4th generation cephalosporins and quinolones are risk factors; though that does not mean another antibiotic may also be the cause of infection.
Post-antibiotic treatment, the normal flora of the bowel reconstitute in 204 weeks. This occurs through food and bacteria introduced orally and also via the appendix which serves as a reservoir for bacterial flora. Probiotics are not necessary for every patient, but have proven benefits. Here are some numbers regarding probiotic success in reducing the disease; Lactobacillus, 60-65%, Bifidobacterium 80% and Kefir 65% reduction in C. Diff relapses. Dr. Francke recommends Keefer to his patients because it contains 11 of the 14-16 organisms identified to be beneficial in the aforementioned Canadian studies. Dr. Francke noted a decrease in relapse rates from 50-60% to 5-10%, through notes that this is an anecdotal observation.
Positive risk factors, combined with patient complaints of severe watery diarrhea, with or without blood, fever and an elevated white count, raises high suspicion for C. Diff. When suspected a PCR test should be ordered, rather than a stool culture or multiplex test. These would be used when another disease process is suspected. The C. Diff PCR looks for the DNA coding for the production of the toxins, both A and B, but again B is more concerning.
Two instances where PCR testing would not be required is the patient has already tested positive for C. Diff. or the patient has less than 3 stools a day - meaning they are not experiencing significant pathology of the disease.
Not every case of diarrhea is C. Diff, and differential diagnosis would include obtaining imaging - such as CT or X-ray. Colonic distention with edema on the wall of the colon could be seen in a case of C. Diff. If a patient were symptomatic, but the C. Diff PCR was negative, it is not recommended to treat them for C. Diff, as the toxin test has a 98% predictive value.
First line treatment for an initial infection is 125mg of oral vancomycin, 4 times a day for a 10-14 day course. After the first relapse, repeat oral vancomycin, but with longer taper over several weeks. A probiotic can be added at this stage. If a second relapse occurs, consider adding rifaximin or fidaxomicin, and for the severely ill, Bezlotoxumab can be given, which helps decrease the relapse rates. Metronidazole is no longer used as first line treatment due to a high relapse rate.
Oral vancomycin is 72-75% effective for treatment of an initial infection. After the first relapse, vancomycin treatment is again 72-75% effective. After the 2nd relapse, effectiveness is 50-65%. Use of fidaxomicin at any stage is 80-85% effective. Adding rifaximin to oral vancomycin increases effectiveness by 10-15%.
FMT: Fecal Microbiota
Fecal microbiota transplant is a treatment option for C. Diff. Fecal matter is collected from donors carefully screened for infectious disease. Administration to the patient is achieved in one of three ways: One time administration via nasogastric tube or enema or administered via 6-8 oral capsules over several days. Research has shown pre-treatment with Bezlotoxumab increases the effectiveness of FMT by 65-85%. Literature has also shown that a vancomycin taper can increase the success rate of FMT.
Community colonization of C. Diff has increased by 3-5%, but nosocomial infections have decreased. Prevention includes: handwashing with soap, isolation of infected patients, terminals cleans after discharge, and use of UVC light machines.
Antibiotic stewardship is also important and it takes a combined effort to ensure the most efficient and appropriate antimicrobial agents are being used.
For those being treated as outpatients it is most likely that other family members and even pets are already colonized. To prevent reinfection or spread, outpatient education includes, washing linens, wiping down commonly used surfaces with bleach, and hand washing.
Thanks for listening.