Could anyone imagine a medical condition that would warrant a patient receiving a stool specimen from a donor to help treat a disease? Such treatment would seemingly belie the “Above all, do no harm” axiom thought to be part

of medicine's Hippocratic oath.

It just so happens that such an event occurred more than 50 years ago, continues today, and much more often.

In 1958, doctors in Denver, Colorado, administered donor feces by enema to patients with colitis. The goal of infusing donor feces was to re-establish the balance of nature within the intestinal flora to correct the disruption caused by antibiotic treatment. The doctors reported immediate and dramatic responses and concluded that this simple yet rationale method should be given more extensive clinical evaluation.

It took 50 years or so to establish an association between Clostridium difficile infection (CDI) and pseudomembranous enterocolitis and to identify effective antimicrobial treatment methods. Despite these advances, C. difficile became the most commonly identified cause of hospital acquired infectious diarrhea in the United States. The success of fecal transplants in prevention supports the concept that there are microorganisms in feces that reestablish protection.  

Clostridium difficile, the agent that causes pseudo-membranous colitis associated with antibiotic therapy, has been identified in recent years as a common nosocomial (hospital acquired) pathogen. It was first described in 1935. This gram positive anaerobic bacillus was named “the difficult clostridium” because it resisted early attempts at isolation and grew very slowly in culture. Although the organism released potent toxins in broth culture, the fact that it was found in stool specimens from healthy neonates led to its classification as a commensal. (A commensal is an organism that benefits from a symbiotic (associated biologically) relationship with another organism without harming it.) The pathogenicity of C. difficile is rooted in the fact that it is a spore forming toxigenic organism. The spore form is resistant to gastric acid and can therefore readily pass through the stomach to the intestine, where it changes to a vegetative life cycle.

Pseudomembranous colitis was first described in 1893; while the role of C. difficile as the cause of diarrhea was first reported in 1978. Today, the organism is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis.

During the past decade, there has been an alarming increase in the incidence and severity of this disorder, with associated increases in mortality and economic cost. The most common symptoms include watery or bloody diarrhea, fever, loss of appetite, nausea, stomach pain, cramping and tenderness.

The disease strikes 500,00 Americans each year and kills 30,000. It has been reported that 96% of patients with symptomatic infection had received antimicrobials within 14 days before the onset of diarrhea and that all had received an antimicrobial within the previous three months.



The Treatment

There are a number of alternative treatment methods. Metronidazole is the drug of choice for mild to moderate CDI, while vancomycin is used for a severe episode.

Both drugs have a long clinical history. Various regimens have been used and the drugs may be used from two to eight weeks. The purpose of the therapy is to keep C. difficile vegetative forms in check while allowing restoration of a normal flora.

Methods to control infection in the hospital (gloves, gowns, hand hygiene) and environmental cleaning and disinfection are equally important. Cleaning and disinfection are critical as the bacteria is sticky similar to anthrax. Clostridium difficile spores have an exosporium that confers a particulate adherence — chains of protein-containing substances that adhere to hands.



Final Thoughts

Fecal implants are certainly medical oddities but preliminary results have confirmed their effectiveness and are warranted in light of the dire consequences of CDI. According to a recent editorial in the New England Journal of Medicine, a recent report of successful results should encourage and facilitate the design of similar trials for other indications, such as inflammatory bowel disease, irritable bowel syndrome, prevention of colorectal carcinoma and other disorders. As such, fecal implants herald a broad and exciting new branch of human therapeutics.

Before such efforts begin in earnest, the FDA must decide how fecal implants are regulated. According to the New York Times, the heart of the controversy is a question of classification: Are fecal microbiota that cure C. difficile a drug, or are they more like organs, tissues and blood products that are transferred from the healthy to the sick?

The answer will determine how the Food and Drug Administration regulates the procedure, how much it costs and who gets the profit.

Max Sherman is a medical writer and pharmacist retired from the medical device industry. He has taught college courses on regulatory and compliance issues at Ivy Tech, Grace College and Butler University. Sherman has an unquenchable thirst for knowledge on all levels. Eclectic Science, the title of his column, touches on famed doctors and scientists, human senses, aging, various diseases, and little-known facts about many species, including their contributions to scientific research. He can be reached by email at maxsherman339@gmail.com.