Pseudomembranous colitis
Encyclopedia
Pseudomembranous colitis, a cause of antibiotic-associated diarrhea (AAD), is an infection of the colon
. It is often, but not always, caused by the bacterium Clostridium difficile
. Because of this, the informal name C. difficile colitis is also commonly used. The illness is characterized by offensive-smelling diarrhea
, fever
, and abdominal pain
. In severe cases, life-threatening complications can develop, such as toxic megacolon
.
, broad-spectrum antibiotics such as cephalosporin
s, or any penicillin-based antibiotic such as amoxicillin
causes the normal bacterial flora of the bowel to be altered. In particular, when the antibiotic
kills off other competing bacteria in the intestine, any bacteria remaining will have less competition for space and nutrients there. The net effect is to permit much more extensive growth than normal of certain bacteria. Clostridium difficile is one such type of bacterium. In addition to proliferating in the bowel, C. difficile also produces toxins. Without either Toxin A or Toxin B, C. difficile may colonize the gut but is unlikely to cause pseudomembranous colitis.
s. Antibiotics disturb the normal bowel bacterial flora
. Clindamycin
is the antibiotic classically associated with this disorder, but any antibiotic can cause the condition. Even though they are not particularly likely to cause pseudomembranous colitis, due to their very frequent use, cephalosporin
antibiotics (such as cefazolin
and cephalexin) account for a large percentage of cases. Diabetics and the elderly are also at increased risk, although half of cases are not associated with risk factors.
Other risk factors include increasing age and recent major surgery. There is some evidence that proton pump inhibitor
s are a risk factor for C. difficile infection and pseudomembranous colitis, but others question whether this is a false association or statistical artifact (increased PPI use is itself a marker of increased age and co-morbid illness).; indeed, one large case-control study showed that PPIs are not a risk factor.
) may be present. "Constitutional" signs such as fever, fatigue, and loss of appetite are prominent. In fact, one of the main ways of distinguishing pseudomembranous colitis from other antibiotic-associated diarrheal states is that patients with the former are sick. That is, they are often prostrate, lethargic, and in general look unwell. Their "sick" appearance tends to be paralleled by the results of their blood tests, which often show anemia
, an elevated white blood cell count, and low serum albumin
.
Prior to the advent of tests to detect Clostridium difficile toxins, the diagnosis was most often made by colonoscopy
or sigmoidoscopy
. The appearance of "pseudomembranes" on the mucosa of the colon
or rectum
is diagnostic of the condition. The pseudomembranes are composed of an exudate made of inflammatory debris, white blood cells, etc.
Although colonoscopy and sigmoidoscopy are still employed, stool testing for the presence of Clostridium difficile toxins is now often the first-line diagnostic approach. Usually, only two toxins are tested for - Toxin A and Toxin B - but the organism produces several others. This test is not 100% accurate, and there is a considerable false negative rate even with repeat testing.
Another, more recent two-step approach involves testing for the presence of C. Diff in the stool and then testing for toxin production. The first step is performed by testing for the presence of the C. Diff GDH antigen. If the first step is positive, a second test, a PCR assay targeting the toxin genes, is performed.
Cholestyramine and other bile acid resins should not be used as adjunctive therapy because, though they may bind the C. difficile toxin, they can also inhibit the effects of the primary antibiotic.
Several probiotic therapies have been used as adjunct therapies for pseudomembranous colitis. Saccharomyces boulardii
(baker's yeast) has been shown in one small study of 124 patients to reduce the recurrence rate of pseudomembranous colitis. A number of mechanisms have been proposed to explain this effect. Fecal bacteriotherapy
is a medical treatment, which involves restoration of colon homeostasis by reintroducing normal bacterial flora from stool obtained from a healthy donor, has been successfully used to treat acute pseudomembranous colitis.
If antibiotics do not control the infection, the patient may require a colectomy
(removal of the colon) for treatment of the colitis.
using a probiotic
drink containing Lactobacillus casei
, L bulgaricus
, and Streptococcus thermophilus was reported to have some efficacy. This study was, however, sponsored by the company that produces the drink. Although intriguing, several other studies have been unable to demonstrate any benefit of oral supplements of similar bacteria at preventing C. difficile-associated diarrhea (CDAD).
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
. It is often, but not always, caused by the bacterium Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...
. Because of this, the informal name C. difficile colitis is also commonly used. The illness is characterized by offensive-smelling diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, and abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
. In severe cases, life-threatening complications can develop, such as toxic megacolon
Toxic megacolon
Toxic megacolon is an acute form of colonic distension. It is characterized by a very dilated colon , accompanied by abdominal distension , and sometimes fever, abdominal pain, or shock....
.
Mechanism of disease
The use of clindamycinClindamycin
Clindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...
, broad-spectrum antibiotics such as cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
s, or any penicillin-based antibiotic such as amoxicillin
Amoxicillin
Amoxicillin , formerly amoxycillin , and abbreviated amox, is a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral...
causes the normal bacterial flora of the bowel to be altered. In particular, when the antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
kills off other competing bacteria in the intestine, any bacteria remaining will have less competition for space and nutrients there. The net effect is to permit much more extensive growth than normal of certain bacteria. Clostridium difficile is one such type of bacterium. In addition to proliferating in the bowel, C. difficile also produces toxins. Without either Toxin A or Toxin B, C. difficile may colonize the gut but is unlikely to cause pseudomembranous colitis.
Risk factors and epidemiology
In most cases, a patient presenting with pseudomembranous colitis has recently been on antibioticAntibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s. Antibiotics disturb the normal bowel bacterial flora
Flora (microbiology)
In microbiology, flora refers to the collective bacteria and other microorganisms in an ecosystem . While the term microflora is widely used, it is technically a misnomer since the word root flora pertains to the kingdom plantae...
. Clindamycin
Clindamycin
Clindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...
is the antibiotic classically associated with this disorder, but any antibiotic can cause the condition. Even though they are not particularly likely to cause pseudomembranous colitis, due to their very frequent use, cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
antibiotics (such as cefazolin
Cefazolin
Cefazolin , also known as cefazoline or cephazolin, is a first-generation cephalosporin antibiotic.The drug is usually administrated by either intramuscular injection or intravenous infusion .-Indications:Cefazolin is mainly used to treat bacterial infections of the skin...
and cephalexin) account for a large percentage of cases. Diabetics and the elderly are also at increased risk, although half of cases are not associated with risk factors.
Other risk factors include increasing age and recent major surgery. There is some evidence that proton pump inhibitor
Proton pump inhibitor
Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
s are a risk factor for C. difficile infection and pseudomembranous colitis, but others question whether this is a false association or statistical artifact (increased PPI use is itself a marker of increased age and co-morbid illness).; indeed, one large case-control study showed that PPIs are not a risk factor.
Clinical features
As noted above, pseudomembranous colitis is characterized by diarrhea, abdominal pain, and fever. Usually, the diarrhea is non-bloody, although blood may be present if the affected individual is taking blood thinners or has an underlying lower bowel condition such as hemorrhoids. Abdominal pain is almost always present and may be severe. So-called "peritoneal" signs (e.g., rebound tendernessRebound tenderness
Rebound tenderness is a clinical sign that a doctor or other health care provider may detect in physical examination of a patient's abdomen. It refers to pain upon removal of pressure rather than application of pressure to the abdomen...
) may be present. "Constitutional" signs such as fever, fatigue, and loss of appetite are prominent. In fact, one of the main ways of distinguishing pseudomembranous colitis from other antibiotic-associated diarrheal states is that patients with the former are sick. That is, they are often prostrate, lethargic, and in general look unwell. Their "sick" appearance tends to be paralleled by the results of their blood tests, which often show anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, an elevated white blood cell count, and low serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
.
Diagnosis
In order to make the diagnosis, it is, of course, essential that the treating physician be aware of any recent antibiotic usage. The disease may occur as late as six months after antibiotic use. Although there is some relationship between dose/duration of antibiotic and the likelihood of developing pseudomembranous colitis, it may occur even after a single dose of antibiotic. In fact, the use of a single-dose prophylactic antibiotic is a common practice in surgical and dental patients to prevent infections associated with a procedure. Hence, even though unlikely to cause pseudomembranous colitis on a per-case basis, single-dose antibiotic treatment, by virtue of the large number of patients receiving such, is an important cause of pseudomembranous colitis. Use of 'proton pump inhibitor' drugs such as omeprazole for gastric reflux, or some forms of asthma inhaler, in fact, all drugs with anticholinergic effects that slow the digestive transit time lead to retention of toxins and exacerbate the effects of broad-spectrum antibiotics.Prior to the advent of tests to detect Clostridium difficile toxins, the diagnosis was most often made by colonoscopy
Colonoscopy
Colonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
or sigmoidoscopy
Sigmoidoscopy
Sigmoidoscopy From Greek Sigma - eidos - scopy, to look inside an s-like object, is the minimally invasive medical examination of the large intestine from the rectum through the last part of the colon. There are two types of sigmoidoscopy, flexible sigmoidoscopy, which uses a flexible endoscope,...
. The appearance of "pseudomembranes" on the mucosa of the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
or rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
is diagnostic of the condition. The pseudomembranes are composed of an exudate made of inflammatory debris, white blood cells, etc.
Although colonoscopy and sigmoidoscopy are still employed, stool testing for the presence of Clostridium difficile toxins is now often the first-line diagnostic approach. Usually, only two toxins are tested for - Toxin A and Toxin B - but the organism produces several others. This test is not 100% accurate, and there is a considerable false negative rate even with repeat testing.
Another, more recent two-step approach involves testing for the presence of C. Diff in the stool and then testing for toxin production. The first step is performed by testing for the presence of the C. Diff GDH antigen. If the first step is positive, a second test, a PCR assay targeting the toxin genes, is performed.
Treatment
The disease is treated either with oral Vancomycin or with intravenous Metronidazole. Choice of drug depends on severity of disease and the ability to tolerate and absorb oral medications. Vancomycin treatment does present the risk of the development of vancomycin-resistant enterococcus, though it is only minimally absorbed into the blood stream from the gastrointestinal tract. Metronidazole has on occasion been associated with the development of pseudomembranous colitis. In these cases, metronidazole is still an effective treatment, since the cause of the colitis is not the antibiotic, but rather the change in bacterial flora from a previous round of antibiotics. Clostridium Difficile infections that do not respond to Vancomycin or Metronidazole are sometimes treated with Rifaximin orally. Fidaxomycin is a new alternative that has been approved for treatment in mid-2011.Cholestyramine and other bile acid resins should not be used as adjunctive therapy because, though they may bind the C. difficile toxin, they can also inhibit the effects of the primary antibiotic.
Several probiotic therapies have been used as adjunct therapies for pseudomembranous colitis. Saccharomyces boulardii
Saccharomyces boulardii
Saccharomyces boulardii is a tropical strain of yeast first isolated from lychee and mangosteen fruit in 1923 by French scientist Henri Boulard. It is related to, but distinct from, Saccharomyces cerevisiae in several taxonomic, metabolic, and genetic properties. S...
(baker's yeast) has been shown in one small study of 124 patients to reduce the recurrence rate of pseudomembranous colitis. A number of mechanisms have been proposed to explain this effect. Fecal bacteriotherapy
Fecal bacteriotherapy
Fecal bacteriotherapy, also known as fecal transfusion, fecal transplant, stool transplant, or human probiotic infusion , is a medical treatment for patients with pseudomembranous colitis , or ulcerative colitis that involves restoration of colon homeostasis by reintroducing normal bacterial flora...
is a medical treatment, which involves restoration of colon homeostasis by reintroducing normal bacterial flora from stool obtained from a healthy donor, has been successfully used to treat acute pseudomembranous colitis.
If antibiotics do not control the infection, the patient may require a colectomy
Colectomy
Colectomy consists of the surgical resection of any extent of the large intestine .-History:Sir William Arbuthnot-Lane was one of the early proponents of the usefulness of total colectomies, although his overuse of the procedure called the wisdom of the surgery into question.-Indications:Some of...
(removal of the colon) for treatment of the colitis.
Prevention
A randomized controlled trialRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
using a probiotic
Probiotic
Probiotics are live microorganisms thought to be beneficial to the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host"...
drink containing Lactobacillus casei
Lactobacillus casei
Lactobacillus casei is a species of genus Lactobacillus found in the human intestine and mouth. As a lactic acid producer, it has been found to assist in the propagation of desirable bacteria. This particular species of Lactobacillus is documented to have a wide pH and temperature range, and...
, L bulgaricus
Lactobacillus bulgaricus
Lactobacillus delbrueckii subspecies bulgaricus is one of several bacteria used for the production of yogurt. It is also found in other naturally fermented products...
, and Streptococcus thermophilus was reported to have some efficacy. This study was, however, sponsored by the company that produces the drink. Although intriguing, several other studies have been unable to demonstrate any benefit of oral supplements of similar bacteria at preventing C. difficile-associated diarrhea (CDAD).