Chronic Diarrhea After C difficile Eradication
Mona Morstein, ND
Clostridium difficile is the only anaerobe bacteria that causes a nosocomial risk. First identified in 1935, it was not until the 1970s that the C difficile toxins were discovered to cause diarrhea and pseudomembranous colitis.1 In the United States, there are approximately 500 000 new cases of C difficile infection a year, with 28 000 deaths.1 C difficile causes 20-30% of antibiotic-associated diarrhea cases and is the most commonly recognized etiology of infectious diarrhea in healthcare environments, such as long-term care facilities and hospitals. Patients are often elderly individuals who were dosed with antimicrobials. Other risk factors include underlying illnesses (which make patients more susceptible), immunosuppression, tube feeding, and gastric acid suppression, for example, via proton pump inhibitors.2 The health care costs of addressing C difficile through 2007 exceeded $3.8 billion, a substantial and growing amount. Over the last decade, the incidence of patients developing severe disease has drastically increased.
Clostridium difficile is a normal part of the intestinal flora in children younger than 2 years but is not commonly found in any substantial quantity in those 2 years or older.2 Incubation of C difficile is very short post-colonization, and infections generally occur within 2-3 days. There are many different subspecies of C difficile, but the pathogenic strains produce toxin A (enterotoxic) and toxic B (cytotoxic), which cause fluid secretion, mucosal damage, and interstitial inflammation of the intestinal tract. These toxins can affect patients variably, ranging from a mild condition with frequent foul-smelling stools to a colitis presentation with bloody diarrhea, cramps, urgency, and mucus, or the condition of the patient may worsen to develop pseudomembranous colitis, fulminant colitis, megacolon, peritonitis, or death. The latter most severe form of the infection occurs in 3% of patients.2 Extraintestinal symptoms, such as reactive arthritis, are very rare.
Clostridium difficile disease is associated mainly with diarrhea and a specific type of colitis. However, C difficile infection is now also considered an aggravating factor in children falling within the autistic spectrum disorder.1
Clostridium difficile is typically considered a probable infection (1) when a patient develops diarrhea 72 or more hours after admission to the hospital or within 1 month after a previous hospitalization or (2) if a new episode of diarrhea occurs more than 8 weeks after a previous bout of the infection. Antibiotic use that is particularly associated with increased risk of developing C difficile infection includes penicillin, ampicillin, clindamycin, and cephalosporins. It has been reported that 96% of patients with symptomatic C difficile infection had been dosed antibiotics within the last two weeks and that 100% of patients had been dosed antibiotics within the past three months. Other risk factors for patients are receipt of an enema, prolonged use of nasogastric tubes, or gastrointestinal surgery.
In a patient with sudden diarrhea, the physician should submit a sample for C difficile analysis if the following conditions are met: (1) if the patient received an antibiotic up to 2 months before the diarrhea began, (2) if the diarrhea is watery and profuse and the patient has at least 6 bowel movements within 36 hours, and (3) if other causes for the diarrhea have been ruled out.
Treatment for patients who develop C difficile infection includes stopping the antibiotics, if possible, that they are taking for their presenting condition. If those antibiotics cannot be stopped without significant consequences and need to be continued, the risk for patient morbidity and mortality rises drastically. Medications used to treat C difficile infection include metronidazole (500 mg 3 times daily for 10-14 days) and vancomycin (125 mg orally 4 times daily for 10-14 days).3 Rifaximim is starting to be used, as well as fidaxomicin.1 For recurrent infection, one can use the initial medication, but do not use metronidazole more than twice overall to prevent neurotoxicity. Other important treatment components include hand washing before and after eating and after using the bathroom, environmental disinfection (cleaning the bathroom after each use), and fingernail cutting (reinoculation is common).1-3 If the situation continues to deteriorate, a colectomy may be required.3
When treating patients with C difficile, one needs to focus on preventing the spread of infection. Guidelines in hospitals or medical facilities should require healthcare workers and visitors to use gloves and gowns when visiting a patient with C difficile, as soap and water do not wash off spores. However, hand hygiene is vital, and all people who contact a patient with C difficile should wash their hands immediately afterwards with stronger antibacterials. Patients with C difficile should ideally be kept in a single room. Healthcare workers should replace environmental sources of potential infection, such as electronic thermometers with disposable ones, and use effective cleaning agents, such as sodium hypochlorite, to address environmental contamination. Antimicrobials should be used judiciously with an idea of minimizing the frequency and duration.
Chronic Diarrhea After Cured C difficile Infection
Clostridium difficile infection is commonly eradicated by standard care; however, many patients in my experience are still left with lingering diarrhea afterward. I have treated numerous patients who presented to my clinic with continued diarrhea after acquiring C difficile infection during a hospitalization, although all stool samples now clearly show that they are free of C difficile. The ongoing problem with these patients is that all the antibiotic use—the ones that were given in the hospital that led to the C difficile infection and the ones used to treat the C difficile—has caused other bacterial infections aside from C difficile and dysbiosis in general in the gut. In some patients, the gut is harmed such that an acquired food-based diarrhea is produced.
Standard analysis of stool samples obtained by allopaths tends to rely mainly on investigating the stool for simple microorganism panels, primarily consisting of C difficile, Salmonella, and Shigella; the latter 2 are common food-borne pathogens that also cause diarrhea. As naturopaths, we are fortunate in our profession to have alternative laboratories that perform much more comprehensive analyses of stool. Although patients will initially perceive that a stool sample is an unnecessary repetitive test, it is not hard to convince them to send a sample to a laboratory that specializes in stool analyses and can investigate the presence of other microorganisms that standard medical laboratories will not detect. Using these laboratories and naturopathic care, all patients should be cured of their lingering diarrhea.
I have used this protocol for all the patients I have seen with post–C difficile chronic diarrhea. The outcome has been successful in every case.
Naturopathic Investigation of Post–C difficile Chronic Diarrhea
Report of a Case
My last patient with post–C difficile chronic diarrhea was a 78-year-old woman who had developed C difficile infection in a hospital 1 year previously. She had been continually treated with vancomycin for almost a year, with no probiotics suggested. She came to me still having 6 to 12 bowel movements a day and had lost 40 lb, making her very lean, which is especially dangerous in senior patients, exacerbating their frailty and dampening their vital force.
Comprehensive Stool Analysis
The best test to perform in patients with chronic diarrhea after C difficile infection is a comprehensive parasitology panel from any of our specialty laboratories that excel at those investigations. I used Doctor’s Data (comprehensive metabolic panel x3) and discovered that the patient had no toxin-producing C difficile but had the following 3 diarrhea-associated pathogens: 4+ Enterobacteria cloacae, 4+ Citrobacter farmeri, and 4+ Morgenella morganii. She was also low in her beneficial bacteria, having no growth for Bifidobacterium, Lactobacillus, or Bacteroides. I do not recommend performing the comprehensive digestive stool analysis because acquiring the extra information is not really helpful for these patients and simply obtaining the less expensive comprehensive stool analysis is extremely valuable. The sensitivity testing showed that the pathogenic bacteria were sensitive to citric seed extract, uva ursi, and tannins. I also had the patient keep a diet diary.
I suggest that patients keep a 7-day diet diary. Also recommended is any standard laboratory work that seems pertinent, such as nutrient deficiencies from diarrhea.
Small Intestine Bacterial Overgrowth Testing
With the recognition that small intestine bacterial overgrowth (SIBO) can cause diarrhea or constipation, that is now in my back pocket for testing, but I do not start with it. If I am unsuccessful in getting the postinfective diarrhea under control with my protocols and the diarrhea continues, I consider testing for SIBO. However, treatment for SIBO is expensive, complicated, and long-term, and it has not been my experience that patients with chronic diarrhea after cured C difficile infection require that for recovery. The protocol listed in the “Treatments” section has been 100% successful for me, without SIBO investigation and treatment.
We discussed how to address the patient’s basic diet to enhance gut healing via food and drink and to remove irritating, proinflammatory, unhealthy foods. I also recommended lifestyle treatments, such as getting good sleep and maintaining more peace of mind in stressful situations. In addition to multivitamins and fish oils, my specific treatment over the next 2 months included the following:
1. Antimicrobials. The following were positive in the stool sample sensitivity testing for eradicating the aforelisted diarrhea-associated microorganisms: grape seed extract, a capsule blend of caprylic acid, quebracho tannins, berberine sulfate, garlic, and uva ursi; allicin capsules, and freeze-dried uva ursi capsules.
2. Probiotics. Probiotics have been proven to be effective for prevention of antibiotic-associated diarrhea and to be useful with other antimicrobials for treatment of C difficile disease.4-7 Recommended is a mixture of Lactobacillus, Bifidobacillus, and Saccharomyces boulardii (200 billion live bacteria a day).
3. Small bowel healing. Clostridium difficile toxin A has been associated with significant intestinal damage and permeability in the enterocytes, including the development of reactive arthritis.8-13 Therefore, physicians should focus on strengthening the lining of the intestine for some months, continuing even after the stools are back to normal. This is a vital component to fully heal patients with post–C difficile diarrhea.
4. Removal of gluten. Although removal of gluten is not necessarily supported by medical studies, I realized that the patient described herein had developed an intolerance to gluten after all the antibiotics and pathogen infections.11 With the bowel movements markedly improved but not completely back to normal, and after analyzing the patient’s diet and seeing that she consumed gluten frequently, I recommended full avoidance of gluten as a lingering obstacle to cure. I have not had most patients need to do this, so I believe that we should judge each patient on an individual basis in this regard. With this senior patient, her diarrhea finally completely stopped on removing gluten,14 and her bowel movements returned to normal. Dairy is another common food that one has suspicions about in acute and chronic diarrhea, due to lack of lactase production with small intestine temporary atrophy. I seriously watch dairy with patients and consider eliminating it if the medications and basic healthy diet are not fully reversing their condition. Some doctors might consider using the Specific Carbohydrate Diet, but I have never had to recommend that protocol to heal any patient with post–C difficile infection.
5. Hygiene. Recommendations for necessary hygiene are the same as those listed at end of the introductory section herein. These include hand washing, environmental disinfection, and fingernail cutting.
After 2 months, the patient had 1 to 2 well-formed bowel movements a day. We were able to wean her off her antimicrobials, which I did one at a time, and then slowly removed the healing products. She stayed on the gluten-free diet and probiotics.
Mona Morstein, ND is full-time professor at Southwest College of Naturopathic Medicine & Health Sciences (Tempe, Arizona), chair of nutrition, gastroenterology teacher, and supervisor of students in the outpatient clinic. She has a private practice, where she specializes in endocrinology, gastroenterology and women’s healthcare. Dr Morstein is a frequent lecturer throughout North America at diverse conventions and has created her own 2-day comprehensive seminar teaching medical professionals how to use insulin with all types of patients having diabetes.