Patient information: Antibiotic-associated diarrhea (Clostridium difficile)

OVERVIEW

Antibiotic-associated diarrhea refers to diarrhea that develops in a person who is taking or recently took antibiotics. One of the most common causes of antibiotic-associated diarrhea is infection with a bacterium, Clostridium difficile (C. difficile). C. difficile infections are most common in people who are hospitalized, affecting more than 60 hospitalized patients per 100,000 (0.06 percent) 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" and "Patient information: Chronic diarrhea in adults".)

WHAT IS C. DIFFICILE?

C. difficile is a bacterium that is normally found, along with hundreds of thousands of other bacteria, in the intestines of healthy people. Many of these bacteria 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 and other symptoms (see 'C. Difficile symptoms' below.

C. difficile is also found on the surface of objects (eg, door knobs, counters). In the hospital, the bacterium 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. 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. Exposure to people who carry the bacteria 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.
• Past infection with C. difficile — People who have been infected with C. difficile previously have an increased risk of becoming infected again.

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 for two or more days) and mild abdominal cramping.
• In more severe cases, the colon can become inflamed (colitis) or develop patches of raw tissue that can bleed or 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, a low-grade 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 bodywide 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 24 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 "Clinical manifestations and diagnosis of Clostridium difficile infection".)

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 underlying 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 such as metronidazole (Flagyl®) or vancomycin (Vancocin®) 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 up to 10 to 14 days).

Both medications can cause side effects.

• Metronidazole can cause nausea and a metallic taste in the mouth. It is important not to drink alcohol during treatment with metronidazole due to the risk of a serious interaction, which can cause flushing, nausea, thirst, palpitations, chest pain, vertigo, and low blood pressure. Metronidazole also interacts with warfarin (Coumadin®), potentially increasing the risk of bleeding.
• Vancomycin may cause nausea, a bitter taste in the mouth, and vomiting. It is not necessary to avoid alcohol while taking vancomycin, and vancomycin does not interact with warfarin (Coumadin®).

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".)

Some studies have found that probiotics modestly shortened the duration of diarrhea related to antibiotics, but not all patients in these studies had C. difficile [1]. Studies that specifically evaluated whether probiotics can prevent or help treat C. difficile infection have been inconclusive [2]. 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 usually treated in the hospital with an intravenous antibiotic and intravenous fluids. The person is monitored closely for signs of worsening disease. (See "Treatment of antibiotic-associated diarrhea caused by Clostridium difficile".)

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".)

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.

A temporary type of lactose intolerance is common following diarrheal illness; this may last for several weeks to months. Thus, temporary avoidance of lactose-containing foods (eg, ice cream, milk and milk products) may be helpful.

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 RELAPSE

Relapse is defined as a 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).

Relapse occurs in 10 to 25 percent of people who are treated with metronidazole or vancomycin. It is not clear why relapse occurs in some people and not in others. Relapse is distinct from reinfection, which occurs when a person becomes infected a second time. Up to one-half of people who develop recurrent symptoms probably have reinfection rather than relapsing infection. It is not always possible to determine if a person has a relapse or reinfection.

Most relapses occur within one to two weeks after discontinuing antibiotic therapy, although relapses can rarely occur as late as 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:

• The antibiotic may be recommended intermittently (eg, once every two days) as the dose is gradually decreased.
• Treatment may be extended beyond the traditional 10 to 14 days.
• Antibiotics may be used in conjunction with probiotics (see 'Probiotics' above.
• 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 bacteriotherapy 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. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Acute diarrhea in adults
Patient information: Chronic diarrhea in adults
Patient information: Acute diarrhea in children

Professional Level Information:
Clinical manifestations and diagnosis of Clostridium difficile infection
Epidemiology, microbiology, and pathophysiology of Clostridium difficile infection
Fecal bacteriotherapy in the treatment of recurrent Clostridium difficile infection
Prevention and control of Clostridium difficile in hospital and institutional settings
Treatment of antibiotic-associated diarrhea caused by Clostridium difficile
Clostridium difficile and probiotics

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/)

• Centers for Disease Control and Prevention (CDC)

      (www.cdc.gov/ncidod/dhqp/id_Cdiff.html)

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