At least 70% of individuals who ingest the Clostridium difficile spores remain asymptomatic but about 1/3rd of patients do become ill. Symptoms may develop as early as the first day after antibiotic exposure to more than 6 to 8 weeks after completion of antibiotic therapy.

The symptoms of include the following:

• Non-bloody watery diarrhea that may occur 6 to 15 times a day
• Signs of dehydration
• Orthostasis
• Lower abdominal cramps
• Abdominal pain
• Fever
• Leukocytosis
• Abdominal rebound or guarding in severe cases
• Decreased bowel sounds
• Anasarca

• Fever

  He was discharged 4 days after finishing eradication therapy, but fever up and diarrhea appeared on the following day. [ncbi.nlm.nih.gov]

  In some people, a toxin produced by C. difficile causes diarrhea, abdominal pain, severe inflammation of the colon (colitis), fever, an elevated white blood cell count, vomiting, and dehydration. [emedicinehealth.com]

• Fatigue

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 12, 2019 [patientslikeme.com]

  TARGET POPULATION: Ulcerative Colitis Men & Women EQUALLY affected; 1st Occurrance = AGE 20-40 -&- 2nd Occurrance = AGE 60+ SYMPTOMS: Ulcerative Colitis Diarrhea; Rectal bleeding; Abdominal cramps; Malabsorption of H20 & electrolytes; Fatigue; Weight [quizlet.com]

  Stool studies and CT scan aid in diagnosis) Bloody stool Signs of sepsis Sepsis is hard to identify, but some signs and symptoms of it are: Malaise (ill feeling) Fatigue Fever Rapid heart rate Low blood pressure Shock I'm assuming your doctor already [pulsemed.org]

• Malaise

  […] are almost always administered orally and may include any antibiotic, but especially Ampicillin Cephalosporins Clindamycin Lincomycin Clinical Findings Begins within a few days to 6 weeks after antibiotic treatment Diarrhea Abdominal pain Anorexia and malaise [learningradiology.com]

  Other symptoms Fever Nausea Vomiting (rare) Loss of appetite Fatigue Malaise Constipation (rare) The signs and symptoms of dehydration may also be present. [healthhype.com]

  These complaints were accompanied by loss of appetite, weight loss and malaise. [scielo.isciii.es]

  Stool studies and CT scan aid in diagnosis) Bloody stool Signs of sepsis Sepsis is hard to identify, but some signs and symptoms of it are: Malaise (ill feeling) Fatigue Fever Rapid heart rate Low blood pressure Shock I'm assuming your doctor already [pulsemed.org]

• Diarrhea

  Your physician should be notified in order to properly evaluate the diarrhea. [emedicinehealth.com]

  PURPOSE: Pseudomembranous colitis is a severe form of antibiotic-associated diarrhea. However, there have been no reports about the factors that make patients with presumed antibiotic-associated diarrhea susceptible to pseudomembranous colitis. [ncbi.nlm.nih.gov]

  Pseudomembranous colitis is also known as antibiotic-associated colitis or antibiotic-associated diarrhea because the predominant symptom is diarrhea and tends to arise after the use of antibiotics. [healthhype.com]

  Incidence Incidence of antibiotic-associated diarrhea varies from 5-39% depending on the antibiotic type. Pseudomembranous colitis complicates 10% of the cases of antibiotic-associated diarrhea. [slideshare.net]

• Abdominal Pain

  The patient had no further recurrence of diarrhea and abdominal pain. We report here on a case of pseudomembranous colitis associated with rifampin. [ncbi.nlm.nih.gov]

  In some people, a toxin produced by C. difficile causes diarrhea, abdominal pain, severe inflammation of the colon (colitis), fever, an elevated white blood cell count, vomiting, and dehydration. [emedicinehealth.com]

  Nine days after discharge, the patient returned to the emergency department with abdominal pain, vomiting, diarrhea, and hypotension. [nejm.org]

• Abdominal Cramps

  A 73-year-old woman presented with chronic watery diarrhea and abdominal cramping of six weeks' duration. [ncbi.nlm.nih.gov]

  History Profuse watery or mucoid diarrhea +/- bloody, tenesmus, fever, abdominal cramps, tenderness, usually within 1 week of antibiotic therapy. Examination Signs of perforation, peritonitis, sepsis and shock or toxic megacolon. [aci.health.nsw.gov.au]

  The majority of persons experience abdominal cramps and tenderness. Fortunately, the disease can be relatively mild, and resolve after the person stops antibiotic therapy. [disabled-world.com]

  Also, see your doctor anytime you have severe diarrhea, with a fever, painful abdominal cramps, or blood or pus in your stool. [mayoclinic.org]

• Chronic Diarrhea

  Usual symptoms include chronic diarrhea, sometimes with traces of blood and mucus, spastic abdominal pain, increased body temperature, lack of appetite and loss of body weight. [oxy.hr]

  […] debilitating illness without antibiotics Clinical disease is due to toxins ( Clin Microbiol Rev 2005;18:247, Indian J Med Res 2010;131:487 ) Clinical features Symptoms: acute or chronic diarrhea; may cause toxic megacolon and perforation 25% caused by [pathologyoutlines.com]

  Case report An 83 year-old female patient was admitted for several occasions in our institution during the year of 2008 for chronic diarrhea. At first presentation she reported five to seven bowel movements per day, sometimes with bloody stools. [scielo.isciii.es]

  Dear V, This is a similar topic to our chronic diarrhea article (one of the most popular for some time). But it's different. We're dealing with a specific cause of stubborn diarrhea and also the vaginosis. [pulsemed.org]

• Tenesmus

  The clinical picture is characterized by frequent, watery (occasionally bloody) diarrhea, abdominal pain, tenesmus, fever, weakness. Fulminant colitis develops in 3-5% of cases. [hungary.pure.elsevier.com]

  A 52-year-old male presented with rectal bleeding and tenesmus. He had been treated for amebiasis with metronidazole, and had improved. Two weeks later, symptoms recurred, and he was referred to our hospital. [ncbi.nlm.nih.gov]

  History Profuse watery or mucoid diarrhea +/- bloody, tenesmus, fever, abdominal cramps, tenderness, usually within 1 week of antibiotic therapy. Examination Signs of perforation, peritonitis, sepsis and shock or toxic megacolon. [aci.health.nsw.gov.au]

  Gastrointestinal manifestations can be nonspecific and range from abdominal discomfort to diarrhea to tenesmus. [mdedge.com]

  It generally has the symptoms of: Increased frequency of bowel movements Tenesmus (straining to free the stool) Abdominal Pain Stool mixed with mucus, pus, and blood However, the 6 types of Li Ji vary in their symptoms and signs. [pulsemed.org]

• Headache

  Infusion specific adverse reactions reported in ≥0.5% of patients receiving ZINPLAVA and at a frequency greater than placebo were nausea (3%), fatigue (1%), pyrexia (1%), dizziness (1%), headache (2%), dyspnea (1%) and hypertension (1%). [web.archive.org]

  Here's a table for ya: Temp Type of Li Ji Unique Symptoms Herbal Formula Hot Damp-heat Burning sensation in anus, dark scanty urine, fever, irritability, thirst Shao Yao Tang Epidemic toxin Sudden onset, high fever, headache, thirst, irritability Bai [pulsemed.org]

  In the Phase IA study, five mild adverse effects were reported (headache, rhinorrhea, open wound in the left upper leg, elevated serum lipase concentration [value not reported], and elevated serum amylase concentration [value not reported]). [doi.org]

Blood work may show leukocytosis and worsening of kidney function. These two parameters indicate a severe infection and these patients should be treated with oral vancomycin rather than metronidazole. Severe cases may also present with hypokalemia and hypoalbuminemia, elevated BUN and creatinine. Tests for Clostridium difficile and toxin on stool should be done in symptomatic patients only. Asymptomatic patients do not need stool testing. The stools may be positive for blood and leukocytes. Stool culture is most sensitive test but the results are not available immediately. Tests for toxins can be done via ELISA and PCR and repeated testing may be required.

Endoscopy is not routinely done in presence of CDI. It may show the pseudomembranes in patients with severe disease. However, there is a high risk of bowel perforation in acute cases. Computed tomography scanning of the abdomen is performed when the cause of colitis is unknown or another cause is suspected. It may show thickening of colonic wall, ascites, irregular bowel wall and stranding of fat. Plain X-ray is ideal to look for toxic megacolon.

• Gram-Positive Bacteria

  positive bacteria, especially clostridia. [en.wikipedia.org]

  SQ641 is an analogue of capuramycin, a nucleoside-based compound produced by the bacterium Streptomyces griseus. 6 Its primary mechanism of action is the inhibition of translocase (TL1), a key regulator of cell wall synthesis in Gram-positive bacteria [doi.org]

  Cody, a global regulator of stationary phase and virulence in Gram-positive bacteria. Curr. Opin. Microbiol. 2005; 8 :203–207. doi: 10.1016/j.mib.2005.01.001. [ PubMed ] [ CrossRef ] [ Google Scholar ] 53. Brekasis D., Paget M.S. [ncbi.nlm.nih.gov]

• Clostridium Difficile Toxin in Stool

  difficile, a normal gut commensal, may produce toxin A, which causes intestinal secretion and acute inflammation Clostridium difficile toxin in stool does not correlate with presence of Clostridia and may not contribute to pathology in intestinal tissues [pathologyoutlines.com]

  Yield of stool culture with isolate toxin testing versus a two-step algorithm including stool toxin testing for detection of toxigenic Clostridium difficile. J Clin Microbiol. 2007;45:3601–5. doi: 10.1128/JCM.01305-07. [doi.org]

• Colitis

  Pseudomembranous colitis is a very severe form of antibiotic associated colitis or diarrhoea. It is usually the result of the toxin of Clostridium difficile. Most cases are hospital-acquired. [gpnotebook.co.uk]

  The histopathological examination was consistent with pseudomembranous colitis. [jmedicalcasereports.com]

• Colonic Ulcer

  Ulcerous colitis is a chronic inflammatory disease that exclusively affects colon. [oxy.hr]

  The colonic epithelium is then more susceptible to ulceration and mucosal necrosis with pseudomembrane development. [mdedge.com]

  Colonic ulcer with exudate and mucus retention. Video Endoscopic Sequence 16 of 30. Digital print pattern of the colonic glands with mucus and exudate. Video Endoscopic Sequence 17 of 30. Colonic ulcer with purulent exudate. [gastrointestinalatlas.com]

While mild cases may be managed by the primary physician severe cases may need to be treated in conjunction with a gastroenterologist and a surgeon. Asymptomatic carriers require no treatment.

Basic treatment includes the following:

• Hydrate orally or intravenously
• Replace electrolytes
• Review the need for PPI
• Treatment must include discontinuation of the precipitating antibiotic as soon as possible. 
• Antidiarrheal agents like lomotil or loperamide should be avoided as they can increase severity and duration of symptoms
• For mild to moderate cases without fever or abdominal pain, discontinuation of the antibiotics may be effective. This type of approach reduces risk of relapse and allows the colonic bacteria to replenish.

Pharmacological treatment

Medical treatment then depends on the severity of the colitis. For mild to moderate colitis, metronidazole is the treatment of choice and administered orally for 10 to 14 days. Severe colitis may require vancomycin four times a day for 10 to 14 days. Fidaxomicin is a newer drug which is as effective as vancomycin with lower rates of recurrence. The cost of fidaxomicin is the limiting factor. A ten day course is close to $3,000.

Fecal transplants are also recommended for chronic relapsing cases. These transplants are about 90% effective. Fecal transplant is performed by transferring stools of a healthy donor into a patient with recurrent CDI to replenish the normal bacterial flora. Fecal transplants are done in three ways, retention enema, colonoscopy and nasogastric tube. Long term data following fecal transplantation reveal that relapse rates are low. There are some studies which show that fecal transplants may be more effective than antibiotics in recurrent cases of CDI. However it should be noted that fecal transplants can transmit infections like HIV, hepatitis and other retroviruses. So the donor must be carefully selected and screened for infectious diseases [11].

The use of probiotics is heavily promoted for treatment of Clostridium difficile colitis. Probiotics contain live nonpathogenic organisms. Unfortunately there is no consensus on the efficiency of probiotics. Even when they do work, less than 60% of patients benefit from probiotics. Some evidence suggests that certain probiotic strains, such as certain Lactobacillus species, and Saccharomyces boulardii, are effective in preventing CDI, but the evidence is inconclusive. It appears that finding the right combination of probiotics instead of a single organism will be necessary to prevent and treat CDI. Probiotics may be used as a preventive measure but there is no evidence that they are effective in acute cases of CDI.

Surgical treatment

Patient with fulminant colitis and toxic megacolon may require emergent surgery. The colon may have to be resected and a colostomy is performed. The decision to operate requires experience as these individuals are critically ill and have a high mortality rate. In general, these patients have elevated levels of lactate, leukocytosis and acute renal failure.

Relapse

Relapse rates of 15 to 30% have been reported after treatment for CDI. The relapse may occur anywhere from 3 days to 3 weeks after treatment is stopped. Reasons for relapse include continued antibiotic exposure, reinfection from the environment and failure to eradicate the organism from the gastrointestinal tract. Management of the first relapse is the same as the initial episode, but the severity of the relapse needs to be clarified. For mild cases of relapse, metronidazole can be used but for severe and subsequent recurrence long term therapy with metronidazole may result in adverse drug effects. Vancomycin is recommended for later recurrences using a pulse or a tapered regimen.

The majority of patients with pseudomembranous colitis do recover without adverse sequalae. Most patients require hydration for a few days. Patients with severe colitis may have adverse outcomes depending on their response to treatment. For those who fail medical therapy and require surgery, the prognosis is guarded. Some of these patients may require a permanent colostomy and may develop multiple organ failure.

The majority of pseudomembranous colitis cases are associated with some type of prior healthcare related exposure. Antibiotic use is the most important risk factor. Antibiotics disrupt the normal protective bacterial flora in the gastrointestinal tract. Even a short term exposure to antibiotics can increase the patients risk which increases with the duration of antibiotic usage. The risk remains high after two months of usage even after discontinuation. 

Outpatient visits to healthcare workers have been linked to the disorder. Since outpatient clinics may not always be regularly disinfected, the environment is easily contaminated with Clostridium difficile spores. Many patients who are infected or colonized, followup up with their primary physicians after discharge and some of these patients continue to shed spores even after completing treatment of Clostridium difficile. The heaviest spore contamination is often found in bathrooms, surfaces, tables and chairs touched by the patient. More important healthcare workers can also transport the spores on their hands and clothes to hospitals and into their homes.

Contact with colonized patients is also a risk factor for community acquired CDI, it is estimated that anywhere from 20 - 50% of asymptomatic patients in hospitals and long term healthcare facilities are colonized with Clostridium difficile. In addition, toddlers and infants can also be asymptomatic carriers. Thus coming into contact with feces or other objects can lead to transmission of spores.

Long term use of proton pump inhibitors (PPIs) is also associated with a high risk of CDI. Almost all PPIs studies have been shown to have a high risk for acquiring CDI. The increase availability of PP over the counter is of public concern [6].

Risk factors with questionable evidence

Even though Clostridium difficile has been found in meat and some vegetable there role of food in transmission of spores is questionable. It should be noted that the spores of Clostridium difficile can survive temperature used to cook and store frozen foods.

Even though Clostridium difficile is found in healthy dogs and cats, there is no solid evidence that direct transmission of this pathogen can occur from animals to humans.

Antidepressant medications like mirtazapine (Remeron) and fluoxetine (Prozac) have been linked to a high risk of CDI. However, the relationship is not direct and it is not known if there are other factors linked.

One study found that obese individuals were more prone to CDI than the general population. It may be that in obese individuals the gut bacteria are altered.

Use of alcohol-based hand sanitizers is widespread in hospitals and it is believed that Clostridium difficile spores have built up resistance to this disinfectant. In addition, there is a belief that spores may be more likely to be transferred in healthcare workers who use this sanitizers. Unfortunately no study has shown that this occurs.

Risk factors

Hospital-acquired

• Advanced age (older than 65)
• Antimicrobial use
• Prior hospitalization
• Nasogastric tubes
• Gastrointestinal surgery
• Immunosuppression and inflammatory bowel disease

Community-acquired [7]

• Antimicrobial exposure
• Outpatient visits to the physician
• Close contact with an infected or colonized individual
• Proton pump inhibitor use
• Foodborne or zoonotic transmission 
• Antidepressant medications
• Obesity [8]

Clostridium difficile infection has changed over the past decade in terms of its epidemiology. There are more reported cases of the infection, the severity of the illness has increased and there are more treatment failures than in the past. Deaths and hospitalizations related to CDI have increased significantly over the past 2 decades. The majority of CDI outbreaks have their onset outside hospitals and most start in nursing home patients or in outpatient settings.

Unlike the past, populations that traditionally have been considered to be at low risk, like young healthy adults and children are also developing CDI and many affected individuals lack the predisposing factors such as advanced age, antibiotic exposure or a recent hospital stay. Healthcare workers must be aware of the change in demographics of the patient population now at risk for CDI.

In the USA there are about 3 million cases of CDI every year. Of these at least 14,000 people die from the infection. Over the past 2 decades, the rates of CDI have dramatically increased. This is a common observation not only in the USA but globally. Overall CDI is more common in elderly people [9] [10].

Regardless of whether the infection develops in the community or hospital, CDI is transmitted by via oral fecal contact from an infected individual to non-infected sources through ingestion of spores. The Clostridium difficile spores are durable outside the human body and persist for months. People who come into contact with them can easily ingest them. Initially the spores are not infectious until they are ingested and germinate. The ingested spore may remain dormant in the gastrointestinal tract until prolonged use of antibiotics may decrease the normal bacterial flora and this allows for the Clostridium difficile to overgrow rapidly.

The symptoms of the condition are produced by two major toxins – toxin A and toxin B. These protein molecules cause inflammation and damage to the mucosal lining of the colon. Toxin B is chiefly responsible for the colon injury and the virulence. Recently a third toxin (BI/NAP1/027) was discovered and it is associated with the most severe colitis, highest rate of recurrence and mortality. The NAP1 strain is known to produce many spores which are much more toxic than the other strains. In addition, the extra spores also result in a higher risk of transmission. The proliferation of the NAP1 strain has been associated with widespread use of the 4th generation fluoroquinolone antibiotics like moxifloxacin and gatifloxacin, but virtually all antibiotics have been shown to provoke Clostridium difficile overgrowth in the colon.

Preventing CDI is not easy. Isolating infected patients is not always possible in nursing homes. However, once a patient has been diagnosed with CDI, the following recommendations apply:

• Use contact precautions for individuals with suspected or confirmed CDI until diarrhea resolves. Wear gloves before entering the patient’s room and take them off before exiting the room. Since the room environment of a patient can become contaminated with spores for many months, the surface should be cleaned daily with a chlorine-based or sporicidal cleaning agent.
• Hand hygiene to be maintained with regular use of soap and water. Alcohol-based hand sanitizers cannot remove spores completely from hands.
• Infected patients should not be allowed to share toilets and personal care products with other patients. A bedside commode with a plastic liner can reduce exposure to the healthcare workers. Use of disposable bedpans is recommended.
• Avoid use of of rectal thermometers and other medical devices or equipment, such as stethoscopes and blood pressure cuffs, between infected and noninfected residents. Equipment should be dedicated to the infected patients with CDI or disinfected before use with other residents.
• Patients should only be allowed out of their room if the diarrhea is contained. They should be taught and educated about washing hands. Patient should wear a clean gown over their clothes and ambulatory devices. 
• All rooms should be disinfected when the patient is discharged.
• Antibiotic use by healthcare workers should be minimized.
• Reduce the need for PPIs.
• Once an outbreak has occurred, all bathrooms should be cleaned with a chlorine disinfectant, tables, door knobs and table should be wiped.
• All healthcare workers should pay attention to infection control measures and practice regular hand washing.
• Communication and education of fellow healthcare workers is vital to prevent outbreaks.

Clostridium difficile is a gram positive spore-forming anaerobic organism that is known to cause antibiotic-associated diarrhea and colitis. Clostridium difficile infection (CDI) can present with mild to severe non-bloody diarrhea with abdominal cramps. While once Clostridium difficile colitis was strictly a nosocomial infection, this is no longer true. An increasing number of cases have now been recognized in the community and it appears that several strains of Clostridium difficile exist with varying degrees of potency. In the past CDI was once only a hospital acquired infection but recent studies indicate that today anywhere from 20-45 percent of cases are community acquired. In fact at least 5% of patients with CDI have no history of recent health setting exposure.

The symptoms of the disorder may occur anywhere from 2-21 days after the antibiotic was discontinued. On sigmoidoscopy one may visualize pseudomembranes attached to the intestinal mucosa. In rare cases, CDI can present with abdominal distention, pain and life threatening colitis (toxic colitis) [1] [2] [3] [4].

Currently CDI cases are categorized as follows:

• Healthcare facility-onset (HCF-CDI): Symptom onset occurs more than 48 hours after admission to a healthcare facility and before dismissal from a healthcare facility.
• Community-onset CDI (CO-CDI): Onset of disease symptoms occurs more than 12 weeks (90 days) after the last discharge from a hospital or within 48 hours of admission to a hospital. 
• Community-onset, healthcare facility-associated CDI (CO-HCFA): Onset of disease symptoms occurs in CDI patients who have had exposure to healthcare facilities in the previous four weeks [5].

Pseudomembranous colitis is a medical disorder of antibiotic-associated diarrhea, usually caused by Clostridium difficile. The use of antibiotics is the number one risk factor for the development of the condition. One may develop profuse watery diarrhea and abdominal cramps. In some cases, discontinuation of the antibiotics helps resolve the condition. In other cases, the patient may need to take specific antibiotics for 10 to 14 days to kill the harmful bacteria. In rare cases, some patients may require surgery to remove the diseased colon. People who develop the disorder can easily transmit the infection to others and thus, hand washing regularly is recommended. At home, it is important to wipe all inanimate objects with a sanitizer and offer the individual a personal commode. The majority of patients who are treated promptly do recover within 2 to 4 days. Unfortunately, relapses can occur and require more specific antibiotic treatment.

1. Guide to preventing Clostridium difficile infections. Association for Professionals in Infection Control and Epidemiology Website. Published 2013. 
2. Lee L, Cohen SH. Community-acquired Clostridium difficile infections: an emerging problem. Curr Emerg Hosp Med Rep. 2013;1:149-153
3. Cole SA, Stahl TJ. Persistent and Recurrent Clostridium difficile Colitis.Clin Colon Rectal Surg. 2015 Jun;28(2):65-9
4. Hasty R, Barbato V, Valdes P, Sitler C. Clostridium difficile colitis, treatment and management. Curr Emerg Hosp Med Rep. 2013;1:141-144
5. Jury LA, Sitzlar B, Kundrapu S, et al. Outpatient healthcare settings and transmission of Clostridium difficile, 2013. PLoS One. 2013;8(7):e70175.
6. McDonald EG, Milligan J, Frenette C, Lee TC. Continuous Proton Pump Inhibitor Therapy and the Associated Risk of Recurrent Clostridium difficile Infection. JAMA Intern Med. 2015 May 1;175(5):784-9
7. Freedberg DE, Abrams JA. Clostridium difficile infection in the community: are proton pump inhibitors to blame? World J Gastroenterol. 2013;19(40):6710-6713.
8. Punni E, Pula JL, Asslo F, Baddoura W, DeBari VA. Is obesity a risk factor for Clostridium difficile infection? Obes Res Clin Pract. 2015 Jan-Feb;9(1):50-4.
9. Kim JH, Toy D, Muder RR. Clostridium difficile infection in a long-term care facility: hospital-associated illness compared with long-term care-associated illness. Infect Control Hosp Epidemiol. 2011;32(7):656-660.
10. Mylotte JM, Russell S, Sackett B, et al. Surveillance for Clostridium difficile infection in nursing homes. J Am Geriatric Soc. 2013;61:122-125.
11. Bakken JS.Feces transplantation for recurrent Clostridium difficile infection: US experience and recommendations.Microb Ecol Health Dis. 2015 May 29;26:27657