Clostridium Difficile, (C-Difficile)

Clostridium Difficile

(Antibiotic Diarrhea)

Antibiotics are medications that kill bacteria. Since their discovery over fifty years ago, antibiotics have certainly been a key factor in keeping us healthy. Their ability to fight infection has saved countless lives. But, there is a downside as well. As with all powerful medications, side effects may sometimes occur. Often, this will take the form of an allergic reaction such as a skin rash. Another side effect that is less well recognized is diarrhea. This is often called antibiotic-associated diarrhea. Other names for this condition are antibiotic-associated colitis, pseudomembranous colitis, or Clostridium difficile colitis.

Good Versus Evil

The problem is one of imbalance. The digestive tract is sterile at birth. Within a few hours, bacteria from the environment enter the intestines. Within a few weeks, these bacterial are well established and are present for life. The colon, or large intestine, normally contains trillions of bacteria that live and multiply happily within the colon. In fact, there are more intestinal bacteria in your colon at this moment than there are human beings who have ever lived. In fact, an average adults harbors more than 400 distinct species of bacteria. Most of these are considered "healthy bacteria." They do not bother you and you don't bother them. All is in balance. A small percentage of these bacteria are harmful - but they are kept in check by all of the healthy bacteria.

A good analogy would be your lawn. If your lawn is healthy, it has few weeds. The thick blades of grass suppress any weeds. But if there is a drought and your grass thins out, weeds will take over. In your colon, the normal healthy bacteria suppress any disease causing germs. However, sometimes when you take antibiotics, the number of healthy bacteria decreases, thus allowing harmful bacteria an opportunity to flourish.


Risk Factors

Certain situations can raise the
risk of Clostridium difficile colitis:
  • Recent antibiotic use
  • Elderly age
  • Kidney failure
  • Burn patients
  • Abdominal surgery
  • Chemotherapy
  • Immunocompromised
  • ICU patients

There happens to be a certain harmful bacteria called Clostridium difficile (abreviated as C. difficile) which may normally be present in some individuals in small numbers. It is estimated that about 20% of hospitalized patients and 1 - 3% of normal individuals harbor this bacteria within their colon as inactive spores. In this "carrier state" there are no symptoms. However, if antibiotics therapy sufficiently suppresses the healthy bacteria in the colon, the C. difficile spores may be allowed to gerninate and multiply. It then produces a toxic substance that causes diarrhea. In high concentrations, this toxin may actually damage the wall of the colon - sometimes severely. First described in 1935, C. difficile was not implicated as a disease bacteria until the 1970's. Now because of the widespread use of antibiotics, C. difficile associated diarrhea has become a common problem with pronounced medical and economic effects.

Which Antibiotics Cause This Problem?

Each antibiotic has a different chemical structure which affects the way it works in the body. Some are more powerful than others, but any antibiotic can suppress the healthy bacteria in your colon. Usually this problem surfaces when the newer, more powerful antibiotics are prescribed, or when multiple antibiotics are used for serious infections. Almost any antibiotic can be cause this infection, but these have been implicated in most cases.

Cleocin (clindamycin)
Lincocin (lincomycin)
Omnipen (ampicillin)

1st generation cephalosporins

Ancef (cefazolin)
Duricef (cefidroxil)
Keflex (cephalexin)
Keflin (cephalothin)
Keftab (cephalexin)
Velosef (cephradine)

2nd generation cephalosporins

Ceclor (cefaclor)
Cefotan (cefotetan)
Ceftin (cefuroxime)
Cefzil (cefprozil)
Kefurox (cefuroxime)
Lorabid (loracarbef)
Mefoxin (cefoxitin)
Mefoxin (cefoxitin)
Zefazone (cefmetazole)
Zinacef (cefuroxime)

3rd generation cephalosporins

Cedax (ceftibuten) Cefizox (ceftizoxime) Cefobid (cefoperazone) Claforan (cefotaxime)
Fortaz (ceftazidime)
Maxipime (cefepime)
Omnicef (cefdinir)
Rocephin (ceftriaxone)
Suprax (cefixime)
Tazicef (ceftazidime)
Vantin (cefpodoxime)

The aminoglycosides (Amikin, Garamycin, Tobramycin), erythromycin (E-mycin, E.E.S), trimethoprim-sulfamethoxazole (Septra DS), and the newer fluoroquinolones (Cipro, Floxin, Levaquin, Maxaquin, Tequin, Trovan) seem less likely to be the cause. The risk of antibiotic associated diarrhea also rises with how often and how long the antibiotics are taken. However, even the most gentle antibiotics, given for a short period of time, can occasionally lead to this problem.

How Soon Do Symptoms Occur?

Again there is much variation. Antibiotic associated diarrhea can occur within two days of completing a course of antibiotics or even up to six weeks later. Therefore, if you have new symptoms of diarrhea, it is important that you make your doctor aware of any antibiotics you may have taken in the last several months.

What Are The Symptoms?

Most patients with this problem notice an unexplained change in bowel habit. The stools become less formed, often loose and watery. There may be nausea, fever, and abdominal pain in severe cases. There is often much urgency with the bowel movement and an unusually foul odor.


    A mild case may be defined as having 5 to 10 watery bowel movements per day, no significant fever, and only mild abdominal cramps. Blood tests may show a mild rise in the white blood cell count (WBC) up to 15,000. (Normal up to 10,000)

    Severe cases may experience more than 10 watery stools per day, nausea, vomiting, high fever 102-104 F, rectal bleeding, severe abdominal pain with much tenderness, abdominal distention, and a high white blood count of 15-40,000.

How Is This Condition Diagnosed?

In general, C. difficile is non-invasive. That means that the organism does not go directly through the intestinal wall into the blood stream. Rather, it stays within the hollow of the intestinal space and causes damage by producing two toxins (Toxin A and Toxin B) that attack the intestinal wall. The presence of these two toxins in the stool is the hallmark of this disease. The diagnosis can usually be made by testing a fresh stool specimen for the presence of these toxins. The toxin assay can miss up to 25% of cases, however, so a normal test does not completetly rule out the diagnosis.

In severe cases, the lining of the colon may actually be damaged and a flexible sigmoidoscopy (short scope) or colonoscopy (full scope) test may be helpful in making the diagnosis and assessing the degree of damage. What the doctor is looking for are characteristic yellowish placques that form on the inner colon lining called "pseudomembranes, hence the term "pseudomembranous colitis." Here you can see four different stages of pseudomembranous colitis caused by C. difficile infection as seen at flexible sigmoidoscopy. Compare this to the normal colon appearance.

How Is This Condition Treated?

The most important aspect of treatment would be to limit the use of powerful antibiotics, particularly when the symptoms of diarrhea occur. By stopping the offending antibiotics under the supervision of your doctor, the normal healthy intestinal bacteria can again multiply and repopulate the colon. Of course, this is not always possible. In more severe cases, additional therapy might include the following:

  • Flagyl
    In more severe cases, one of two special antibiotics may be prescribed. These antibiotics have the opposite effect. They selectively kill the C. difficile organism allowing the normal bacteria to flourish. The most commonly prescribed antibiotic is Flagyl (metronidazole). This can be given orally or in severe cases, by vein. Flagyl is an inexpensive and effective treatment and is the first line of treatment. The oral dose is 250-500 mg four times a day for 7 to 10 days. It does have potential side effects (nausea, vomiting, upset stomach, metalic taste, numbness) and cannot be used in children or pregnant women.
  • Vancocin
    Vancocin (vancomycin) is also an effect treatment, but much more expensive (about $4 a pill). The recommeded dose is 125 mg every 6 hours for 7 to 14 days which achieves a success rate of over 90%. A higher dose of 250 mg to 500 mg every 6 hours is often used in severe cases. Because vancomycin is poorly absorbed by the intestines, high stool concentrations can be acheived without signigicant side effects. One problem besides the expense, however, is the use of this antibiotic can lead to emergence of Vancomycin-Resistant Enterococcus (VRE) within the hospital. Vancomycin-Resistant Enterococcus is a mutant strain of Enterococcus that originally developed in individuals who were exposed to the antibiotic. It was first identified in Europe in 1986, and in the U.S. in 1988 It is not dangerous in healthy people with strong immune systems, where the balance of healthy flora in their digestive tract helps keep VRE from getting out of control. VRE is dangerous because it cannot be controlled with antibiotics, and it causes life-threatening infections in people with compromised immune systems - the very young, the very old, and the very ill. For this reason, vanomycin use is somewhat restricted in most hospitals.
  • Cholestyramine
    Cholestyramine resin (Questran, LoCholest, Cholestid) is sometimes used as additional therapy. This medication is marketed to reduce high blood cholesterol, but also has the ability to absorb and neutralize the C. difficile toxins within the stool. This is best for mild disease or as an adjunt in reoccurence. Constipation is the main side effect. It also binds drugs and cannot be taken at the same time as other prescription medications (including vancomycin and flagyl).
  • Avoid antidiarrheals
    Of course, another important aspect of therapy would be to correct any dehydration which has occurred because of the diarrhea. It is important, however, to avoid antidiarrheal medications since diarrhea is basically nature's way of purging the toxin from the colon. If antidiarrheal medications are taken, this allows the toxin to remain in the colon for prolonged periods of time, thus worsening the situation.
  • Probiotics
    There may also be some benefit in using Lactobacillus bacteria which is found in acidophilus milk or any yogurt with active culture. Evidence suggests that such products may help repopulate the colon with normal, healthy bacteria and speed recovery. Other probiotics that may be of benefit are Culturelle (lactobacillus GG) and Florastor (Saccharomyces boulardii).
  • Good Hygiene
    In an institutionalized setting, such as a hospital, it is also important to prevent the spread of this C. difficile bacteria since it is present in the diarrheal stools. The bacteria can form a spore which may remain infectious despite the use of conventional disinfectants. The spore can survive extreme environmental conditions and persist for months or years outside the body.
  • Surgical Colectomy
    Surgery is rarely needed in C. difficile colitis - less than 5% of cases. Most individuals respond to medical therapy. But in severe life threatening situations that do not respond to the above treatment, surgical removal of the entire colon (total abdominal colectomy) may be lifesaving. Of course, this mandates a permanent ileostomy ("bag") for the colletion of stool, so this decision is not made lightly.

After treatment, patients may become carriers of the C. difficile spore, but most never have a relapse of symptoms. But, about 10% to 20% of patients will experience relapse - regardles of what treatment was given. They usually respond to retreatment, but then the risk of further relapses is high.

How Can I Prevent This Problem?

While there is no guaranteed way to prevent antibiotic associated diarrhea, some simple measures are helpful. The most obvious would be to avoid the unnecessary use of antibiotics for simple infections. Have you ever asked your doctor for antibiotics to treat a cold or the flu? These viral infections do not respond to antibiotics, yet antibiotics are often requested. They should not be utilized. You should tell your doctor if you have ever had C. difficile colitis since past episodes increase your risk of future attacks.

Another preventative measure, particularly within institutions such as hospitals and nursing homes, is the isolation of patients who harbor this infection and careful handwashing and other hygiene techniques.

Lastly, early diagnosis is best. If you have recently received antibiotics and have a significant change in bowel habit, you should see your doctor earlier rather than later since if untreated, late stages of this disease can be quite devastating and occasionally requires surgical removal of the colon.

What About The Future? As the use of antibiotics increases, the incidence of C. difficile infection escalates. The future hope is that a vaccine will become available to immunize high-risk patients. Much research is being done in this area since C. difficile infections are quite costly in today's health care system If you have any additional questions about this condition, you should discuss this with your physician.


  • Don't insist on a prescription for an antibiotic if you have a viral infection such as a cold or flu.
  • Follow your doctor's instructions carefully. Take doses on schedule for the number of days indicated.
  • Let you doctor know if you develop symptoms of persistent diarrhea during or within 6 weeks after a course of antibiotics.
  • Never share your antibiotics with anyone. If you have any left over, throw them away.
  • As with all medications, keep your antibiotics out of children's reach.
Pseudomembranous Colitis Stage 1
Pseudomembranous Colitis Stage 2
Pseudomembranous Colitis Stage 3
Pseudomembranous Colitis Stage 4

Text & Images Courtesy of Three Rivers Endoscopy Center
© Dr. Robert Fusco, Three Rivers Endoscopy Center, All Rights Reserved

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