Clostridium difficile by Gage Anderson
On September 6th, 2019 a middle-aged male was admitted to the inpatient orthopedic center as he recovered from a spinal fusion. While recovering the patient began to experience loose stool or diarrhea. An Enzyme Immunoassay and Glutamate dehydrogenase test were immediately administered as UC Health tests all patients that exhibit, or mention loose stool at least three times a day for clostridium difficile or C-diff to prevent the spread of the infection. Upon examination of test results, the patient was diagnosed with a C-diff infection or CDI and contact precautions were taken. This paper will discuss the epidemiology, symptoms, transmission, causes, diagnosis, and treatment of a clostridium difficile infection.
Clostridium difficile is classified as an anaerobic, gram-positive, spore-forming rod that has the ability to produce exotoxins which puts it in the same family as other deadly bacteria like Clostridium tetani, Clostridium botulinum. This bacterium and its spores are ubiquitous or relatively abundant and can be found on many surfaces, animal feces, human feces, soil, and is even a part of the natural gut microflora for 3% of humans (2). CDI is caused by a dysbiosis in gut bacteria usually as a result of long-term exposure to broadband antibiotics (4). CDI is considered to be one of the more severe forms of antibiotic-associated diarrhea (AAD) and is responsible for 20-30% of AAD cases (1). While diarrhea at least 3 times daily is considered the most common symptom of CDI the infection can cause a variety of symptoms depending on the severity of the infection. These other symptoms include abdominal pain, fever, elevated heart rate, dehydration, and colitis (3). Additionally, CDI can have complications like kidney failure, toxic megacolon and bowel perforation that can lead to death in some cases (3). The CDC estimates that C-diff infects nearly 500,000 patients a year and is responsible for nearly 15,000 deaths annually with an estimated annual cost of 4-4.8 billion (4). The key patients at risk for contracting CDI are patients age 65 and over in nursing Homes or extended care facilities as they account for 2 out of every 3 healthcare-associated CDI’s (2).
C-diff is spread through a fecal orals route and while C-diff is ubiquitous the majority of CDI cases are acquired during a hospital stay rather than outside of a hospital (2). While much of this is due to the antibiotic usage in hospitals, C-diff has specific features that allow it to be transmitted extremely easily in settings like hospitals. Generally, most bacteria that are obligatory anaerobes would die in the presence of oxygen but C diff being a gram-positive bacterium has acquired an ability that allows it to protect itself from environments generally not suitable for growth. C-diff has the ability to sporulate, which means any time the bacteria senses a lack of nourishment, unsuitable temperatures or oxygen content the bacteria can essentially compact and dehydrate all of its DNA into a shell that’s reinforced by minerals like calcium. This compact capsule is known as a spore and makes the bacteria resistant to heat humidity, acidity, alcohol, and many other factors. additionally, this spore has the ability to be transmitted through the air making the containment of this organism extremely difficult. Knowing this many hospitals like UC Health have devolved measures to lessen the spread of C-diff. These measures are called contact precautions and although these measures lessen the spread of C-diff in hospitals, the bacterium often survives on surfaces and hands even after proper sanitization.
Although C-diff is an extremely resistant bacterium that has the ability to easily be transmitted the ingestion of this bacteria rarely results in and infection. That because C-diff relies on a dysbiosis in order to cause an infection. A dysbiosis is an alteration of the proportions of bacteria in the microbiome and is not necessarily the presence or absence of any particular microbe (5). While this definition may seem somewhat vague altering the homeostasis of the intestinal microbiome has massive effects on the body and is linked to many disorders including inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease, asthma, as well as many others (6). For many CDI cases this original dysbiosis is created by broadband antibiotics, which not only wipe out harmful bacteria in the body that could cause infections but also the good bacteria that help with functions like nutrient extraction. Once antibiotics clear out the niches in intestinal epithelial cells that were once held by helpful bacteria C-diff enters the vegetative cycle begins to colonize the large intestine (7). As C diff begins to colonize large intestine the bacteria begins to produce its exotoxins, toxin A, and toxin B, Not all strains produce both, but they do work synergistically. Toxin A binds to the apical side of the epithelial cell and causes a disruption of the tight junction which not only allows both toxins to bind to the basolateral cell membrane but also allows diffusion between the apical and basolateral domains which can cause some of the diarrhea associated with CDI (8,9). Beings both toxins are harmful to living cells they cause a release of cytokines when they attach to the basolateral cell membrane, which leads to increased vascular permeability along with the recruitment of neutrophils and monocytes all of which lead to inflammation, causing the colitis associated with the infection (8).
Diagnosis of CDI can be accomplished through a number of tests, but the most popular would be An Enzyme Immunoassay test for Glutamate dehydrogenase antigen or GDH as it is relatively inexpensive, pretty accurate, and fast (3). This test utilizes antibodies to test for GDH antigens and generally only takes about an hour, however, this test is unable to distinguish toxic from non-toxic strains of C diff (3).
Once diagnosed with CDI the general plan of treatment is to immediately stop any antibiotic treatment that may have led to the CDI and then begin a ten-day cycle of the antibiotic’s vancomycin or fidaxomicin (3). While vancomycin or fidaxomicin are the first line of treatment in CDI cases they may not be the most effective treatment with up <20% of patients experiencing recurrence within the first 30 days (10). Additionally, many patients experiencing recurrence may need long term antibiotic treatment in order to minimize symptoms (10). For patients experiencing recurrence a new controversial treatment has been proposed and has shown great results. That treatment would be Fecal microbiota transplantation or FMT. the process of FMT is basically taking a stool sample from a healthy donor, processing into a liquidized bacterial suspension and planting it into the gut of an infected patient (10). While there have not been many studies conducted on the efficiency of FMT’s in treating CDI, one study was shut down on ethical grounds because over 81% of patients receiving FMT fully recovered versus the 31% of patients receiving vancomycin (10). More severe cases with complications like organ failure may require surgical removal of the infected portion of the large intestine (3).
While CDI seems to effect mostly patients 65 and up, this infection can be extremely serious and should be in the back of anyone’s mind whose taking antibiotics. Anyone whose taking antibiotic and is experiencing diarrhea at least 3 times a day should contact their doctor and start immediate treatment if necessary, to hopefully negate possible complications.
- Mullish B., Williams H. “Clostridium difficile infection and antibiotic-associated diarrhea”., Cline Med (Lond). 2018 Jun; 18(3): 237–241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334067/
- Mada K., Alam M. “Clostridium Difficile.” StatPearls [Internet]., U.S. National Library of Medicine, 4 June 2019, www.ncbi.nlm.nih.gov/books/NBK431054/.
- Mayo Clinic Staff., “C. Difficile Infection.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 26 June 2019, www.mayoclinic.org/diseases-conditions/c-difficile/symptoms-causes/syc-20351691.
- “Nearly Half a Million Americans Suffered from Clostridium Difficile Infections in a Single Year.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 22 Mar. 2017, www.cdc.gov/media/releases/2015/p0225-clostridium-difficile.html.
- Salyers A., Whitt D. Bacterial Pathogenesis: A Molecular Approach . ASM Press. 2002.
- Carding, Simon, et al. “Dysbiosis of the Gut Microbiota in Disease.” Microbial Ecology in Health and Disease, Co-Action Publishing, 2 Feb. 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC4315779/.
- Bien, Justyna, et al. “The Intestinal Microbiota Dysbiosis and Clostridium Difficile Infection: Is There a Relationship with Inflammatory Bowel Disease?” Therapeutic Advances in Gastroenterology, SAGE Publications, Jan. 2013, www.ncbi.nlm.nih.gov/pmc/articles/PMC3539291/.
- Hodges, Kim, and Ravinder Gill. “Infectious Diarrhea: Cellular and Molecular Mechanisms.” Gut Microbes, Landes Bioscience, Jan. 2010, www.ncbi.nlm.nih.gov/pmc/articles/PMC3035144/.
- Takizawa P., “Epithelial Structure”. Leacture slides. Yale School of Medicine. http://medcell.med.yale.edu/lectures/files/epithelial_structure.pdf
- Mullish, Benjamin H, and Horace Rt Williams. “Clostridium Difficile Infection and Antibiotic-Associated Diarrhoea.” Clinical Medicine (London, England), U.S. National Library of Medicine, June 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC6334067/.