Antibiotic-associated diarrhea refers to diarrhea that develops in a person who is taking or recently took antibiotics. One of the most serious causes of antibiotic-associated diarrhea is infection with a bacterium, Clostridium difficile. C. difficile infections are most common in people who are hospitalized, producing disease in more than 8 hospitalized patients per 1000 (0.9 percent) in 2008 in the United States .
This topic review discusses the causes, symptoms, diagnosis, and treatment of C. difficile-associated diarrhea (CDAD). Other types of diarrhea are discussed separately. (See "Patient information: Acute diarrhea in adults (Beyond the Basics)" and "Patient information: Chronic diarrhea in adults (Beyond the Basics)".)
WHAT IS C. DIFFICILE?
C. difficile is a disease-causing bacterium that can infect the large bowel and cause colitis. The intestinal tract of normal people contains millions of bacteria, referred to as the “normal flora,” that have a role in protecting the body from infection. Taking antibiotics can kill these "good" bacteria, allowing C. difficile to multiply and release toxins that damage the cells lining the intestinal wall, causing diarrhea, abdominal pain, and fever, as well as other symptoms (see 'C. Difficile symptoms' below).
C. difficile can be found on the surface of bedside tables, door knobs, counters, lavatories, and sinks in the hospital. The organism can be spread between patients via contact with contaminated objects and/or the hands of healthcare workers. Handwashing is important for preventing the spread of C. difficile infection (see 'Hand washing' below).
C. difficile infections have become more frequent, more severe, more difficult to treat, and more likely to recur after initial treatment. Although most people become infected with C. difficile in the hospital, the infection has also become more common in the community.
C. DIFFICILE RISK FACTORS
A number of factors can increase a person's risk of becoming infected with C. difficile.
- Current or recent hospitalization — Up to 20 percent of people who are hospitalized and up to 50 percent of people in long-term care facilities (eg, nursing homes) carry C. difficile in their feces but many do not have diarrhea or other symptoms. Exposure to these carriers significantly increases a person's risk of becoming infected.
- Current or recent use of antibiotics — Certain antibiotics increase the risk of becoming infected with C. difficile more than others (table 1).
- Older age —The risk of becoming infected with C. difficile is 10 times greater in people who are 65 years or older.
- Severe illness — People who have a weakened immune system as a result of an underlying medical condition or a treatment (eg, chemotherapy) are at increased risk of becoming infected with C. difficile, especially during a hospital stay.
- Recent infection with C. difficile — People who have been recently infected with C. difficile and treated have an increased risk of becoming infected again soon after stopping the treatment.
C. DIFFICILE SYMPTOMS
Symptoms of C. difficile may begin during antibiotic therapy or five to 10 days after the antibiotic is stopped; less commonly, symptoms do not develop until as late as 10 weeks later.
The symptoms of C. difficile can vary in severity:
- Some people (called carriers) carry the bacteria in their feces but have no signs or symptoms of the infection. Carriers can spread the infection to others.
- The most common symptoms include watery diarrhea (three or more times per day, or diarrhea associated with abdominal cramping).
- In more severe cases, the colon can become inflamed (colitis) or develop patches of raw tissue that produce pus (pseudomembranous colitis). Symptoms of these complications can include profuse watery diarrhea (up to 10 to 15 times per day), blood or pus in the stool, dehydration, abdominal tenderness and cramping, fever, nausea, loss of appetite, and weight loss. Anyone who develops one or more of these symptoms should seek medical care as soon as possible.
- Life-threatening complications of C. difficile infection develop in a small number of people. Signs and symptoms of severe infection may include abdominal distension, severe lower abdominal pain, fever (often greater than 101ºF or 38.3ºC), and profuse diarrhea. In rare cases, the bowels can rupture, potentially leading to a body wide infection (sepsis), organ failure, or even death.
C. DIFFICILE DIAGNOSIS
The diagnosis of C. difficile is based upon laboratory analysis of a stool sample. However, the results of laboratory testing are not usually available for several hours. If there is a high suspicion that C. difficile is the cause of a person's symptoms, treatment may be started before the results of the tests are available. (See "Clostridium difficile in adults: Clinical manifestations and diagnosis".)
C. DIFFICILE TREATMENT
The most important step in treatment of C. difficile is to stop the antibiotic that allowed the infection to develop. If an antibiotic is necessary to treat an ongoing infection, the healthcare provider may choose an antibiotic that is less likely to allow further growth of C. difficile, when possible.
Antibiotic treatment — An oral antibiotic is usually recommended to treat people who are infected with C. difficile. It is important to take each dose of the antibiotic on time and to finish the entire course of treatment (usually 10 to 14 days).
Probiotics — Probiotics are "healthy" microorganisms (bacteria, yeast) that can be taken by mouth. Benefits of probiotics have been suggested for several digestive diseases. However, these benefits have been proven only for some types of probiotics in selected situations. (See "Clostridium difficile and probiotics".)
Several studies have found that probiotics reduce the risk for antibiotic-associated diarrhea in general, but their ability to prevent C. difficile infection is unclear. As a result, probiotics are not recommended routinely for diarrhea related to C. difficile, except in selected situations.
While probiotics are generally safe, case reports have described serious illness and deaths related to their use in people who were critically ill or who had a weakened immune system.
Treatment of severe disease — People who become severely ill as a result of C. difficile are treated in the hospital with both oral and intravenous antibiotic and intravenous fluids. The person is monitored closely for signs of worsening disease. (See "Clostridium difficile in adults: Treatment".)
Surgery — If a person fails to improve with antibiotics and supportive care and the infection worsens, surgery may be necessary to remove the infected colon. This procedure is generally limited to people with life-threatening illness.
Supportive treatments for diarrhea — Diarrhea can cause a person to become dehydrated quickly, especially if it is severe. To avoid becoming dehydrated, several strategies are recommended.
Drink adequate fluids — It is important to drink an adequate amount of fluids to counteract the loss of fluids from diarrhea. The fluids should contain water, salt, and sugar. The fluids used for sweat replacement (eg, Gatorade) are not optimal, although they may be sufficient for an adult with diarrhea who is not dehydrated and is otherwise healthy. Diluted fruit juices and flavored soft drinks along with saltine crackers and broths or soups may also be acceptable. Fluid replacement in children should be handled differently. (See "Patient information: Acute diarrhea in children (Beyond the Basics)".)
One way to judge hydration is by observing the color of the urine and how frequently the person urinates. Normally, urine should be light yellow to nearly colorless. A person who is well hydrated normally passes urine every three to five hours. A person who urinates infrequently or has urine that is dark yellow should drink more fluids.
If a person becomes dehydrated and is unable to take fluids by mouth, a rehydration solution can be given into a vein (intravenous fluids) in a healthcare provider's office or in the emergency department.
Diet — There is no particular food or group of foods that is best for a person with diarrhea. However, adequate nutrition is important during an episode of acute diarrhea. For patients without an appetite, it is acceptable to consume only liquids for a short period of time. Boiled starches and cereals (eg, potatoes, noodles, rice, wheat, and oats) with salt are recommended for people with watery diarrhea; crackers, bananas, soup, and boiled vegetables may also be eaten.
C. DIFFICILE PREVENTION
It is uncommon for people who are not taking antibiotics to become infected with C. difficile. However, it is still important to avoid spreading the bacteria. A person can spread the bacteria for as long as the diarrhea continues.
Hand washing — Hand washing is an effective way to prevent the spread of C. difficile. Hands should be washed after using the bathroom and before eating. Hands should ideally be wet with water and plain or antibacterial soap and rubbed together for 15 to 30 seconds. Special attention should be paid to the fingernails, between the fingers, and the wrists. Hands should be rinsed thoroughly and dried with a single use towel. Patients and family members are encouraged to remind healthcare providers to wash their hands, as well.
Alcohol-based hand rubs are less effective against C. difficile and are not recommended alone to prevent the spread of this infection.
Fingernails that are artificial (eg, acrylic) are impossible to clean adequately, even after vigorous scrubbing or use of an antimicrobial soap. For this reason, healthcare workers are not allowed to wear artificial nails.
Contact precautions — People who are hospitalized with C. difficile are placed on contact precautions, which means that anyone who enters the patient's room must wash their hands before entering and after leaving. The person must also wear a clean gown (over their clothes) and clean gloves. These measures can help to prevent the spread of infection to other people in the hospital.
C. DIFFICILE RECURRENCE
Recurrence is defined as resolution of symptoms during treatment followed by a reappearance of diarrhea and other symptoms after treatment is completed. If symptoms return, it is important for a healthcare provider to confirm that C. difficile is the cause of the symptoms (rather than another condition).
Recurrence occurs in 25 percent of people who are treated with metronidazole or vancomycin: in some patients, the recurrence is caused by the original infecting strain, and in others by new infection with a different strain of C. difficile. About one-half of people who develop recurrent symptoms probably have reinfection rather than recurrence. It is not always possible to determine if a person has a recurrence or reinfection.
Most recurrences occur within one to two weeks after discontinuing antibiotic therapy, although rarely recurrence can occur up to two to three months later. People who have at least one episode of recurrent C. difficile have a 50 to 65 percent chance of additional episodes.
Treatment of relapse — A first episode of relapse is treated in the same manner as initial infection (see 'C. Difficile treatment' above). People who develop subsequent relapses of C. difficile (eg, a third or fourth episode) may be treated with one or more of the following strategies:
- Longer treatment with vancomycin that is slowly tapered over a 6 to 12 week period.
- Other antibiotics, such as fidaxomicin or rifaximin, may be used.
- A treatment known as fecal bacteriotherapy may be considered in certain situations. Fecal bacteriotherapy involves giving feces from a healthy person (by enema) to a person who is infected with recurrent C. difficile. This treatment is discussed in detail in a separate article. (See "Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection".)
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient information: Antibiotic-associated diarrhea (C. difficile infection) (The Basics)
Patient information: Probiotics (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient information: Acute diarrhea in adults (Beyond the Basics)
Patient information: Chronic diarrhea in adults (Beyond the Basics)
Patient information: Acute diarrhea in children (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Clostridium difficile in adults: Clinical manifestations and diagnosis
Clostridium difficile in adults: Epidemiology, microbiology, and pathophysiology
Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection
Prevention and control of Clostridium difficile in hospital and institutional settings
Clostridium difficile in adults: Treatment
Clostridium difficile and probiotics
The following organizations also provide reliable health information.
- National Library of Medicine
- Centers for Disease Control and Prevention (CDC)