Clostridium difficile infection overview: Difference between revisions
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==Overview== | ==Overview== | ||
''Clostridium difficile'' | ==Historical Perspective== | ||
''Clostridium difficile'' was first isolated in 1935 during an experiment from [[fecal extract]]s of healthy [[neonate]]s. The association between ''C. difficile'' and antibiotic-associated pseudomembranous colitis was first made in 1978. In 2003, a resistant, [[hypervirulent strain]] of ''C. difficile'' (NAP/BI/027 strain) with increased synthesis of toxins A and B was first identified. | |||
==Pathophyusiology== | |||
Spores of ''C. difficile'' are transmitted via the fecal-oral route to the human host. Spore ingestion may be community-acquired (soil and food) or healthcare-associated (hospitals and clinics). Following ingestion, the acid-resistant spores of ''C. difficile'' are able to survive the human gastric acidity. ''C. difficile'' does not result in clinical manifestations in the majority of cases, whereby normal GI flora resists the growth of ''C. difficile'', and the host immune responses adequately clear the infection before the development of clinical manifestations. However, in susceptible patients, ''C. difficile'' releases 2 major virulence factors: Exotoxins A and B (TcdA and TcdB), which act synergically and mediate adhesion to the colonic mucosa, luminal fluid accumulation, and development of pseudomembranous colitis. These toxins are able to glycosylate Rho GTPase (involved in actin cytoskeleton) and cause the formation of abnormal G-actin (leading to characteristic rounding of cells). Additionally, they stimulate macrophage-induced cytokine production and subsequent neutrophilic infiltration to the site of inflammation, which in part contributes to the disruption of the intestinal barrier and the development of clinical manifestations associated with the infection. On gross examination, colonic pseudomembranes with yellow colored plaque formation are typical. On microscopic examination, erosions within colonic crypts or formation of mushroom-like exudates with hemorrhage and necrosis are characteristic features. | |||
==Causes== | |||
''C. difficile'' infection is caused by ''Clostridium difficile'', a spore-forming, toxin-producing, oligate anaerobic, gram-positive bacillus. | |||
==Classification== | |||
''C. difficile'' infection may be classified based on the clinical severity of the disease. The severity of the infection dictates the choice of [[Clostridium difficile infection medical therapy|antimicrobial therapy]] and the need for surgical consultation/management. Mild disease is defined as isolated [[diarrhea]], whereas severe/complicated disease is defined as either [[delirium]], [[shock]], [[organ failure]], [[high-grade fever]], or marked [[leukocytosis]]. | |||
==Differential Diagnosis== | |||
''Clostridium difficile'' infection must be differentiated from other diseases that cause acute inflammatory diarrhea, abdominal pain, fever, and ileus, including other causes of colitis (ischemic, collagenous, ulcerative), malabsorptive syndromes, diverticulitis, appendicitis, malignancies, drug-induced causes, and infections, such as salmonellosis, shigellosis, or gastrointestinal infections with ''Escherichia coli'' or ''Campylobacter jejuni''. | |||
==Epidemiology and Demographics== | |||
The incidence of ''C. difficile'' infection is estimated to be 20 per 100,000 person-years. In USA, the majority (65%) of cases are associated with healthcare settings, and 25% of cases are associated with previous hospitalizations. Although patients of all age groups may develop ''C. difficile'' infection, elderly patients > 65 years may have up to eight-fold increased risk of developing ''C. difficile'' infection compared with younger patients. Whites and female patients are more predisposed to develop ''C. difficile'' infections. Although ''C. difficile'' is abundantly reported in Europe and the United States, the infection is a global burden. | |||
==Risk Factors== | |||
The most important risk factor for the development of ''C. difficile'' infection is antibiotic use. Although ''C. difficile'' infection has been described with almost all antibiotics, ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones are most classically and most commonly associated with development of ''C. difficile'' infection. Other important risk factors include recent hospitalization (< 12 weeks), advanced age (>65 years), immunodeficiency (primary or secondary causes), inflammatory bowel disease, and exposure to colonized/infected individuals. The association between gastric acid suppression and ''C. difficile'' infection has not been well established. | |||
==Natural History, Complications & Prognosis== | |||
Following ingestion of ''C. difficile'' spores, patients are colonized with the organism. Typically, young healthy individuals with adequate immune responses are able to clear the organism without development of any clinical manifestations. But patients with risk factors, such as recent antibiotic use, recent hospitalization, advanced age, or immunodeficiency, are at an increased risk of developing persistent colonization and/or developing signs and symptoms of the infection. The onset of clinical manifestations may occur within 2 hours up to several months of antibiotic use. Patients typically develop mild/moderate watery diarrhea (possibly bloody) associated with colicky diffuse abdominal pain, nausea, malaise, and fever. If left untreated, patients may develop colitis (with or without pseudomembrane formation). Approximately 3% of patients develop complications, which might be colonic (fulminant colitis) or extracolonic (small intestine invovelemtn, bacteremia, skin infections, reactive arthritis, abscess formation, empyema, or death). The majority of patients with ''C. difficile'' infection recover without sequelae and are responsive to antimicrobial therapy. Nonetheless, ''C. difficile'' is associated with a high lifetime recurrence rate that ranges between 20% to 70%, most of which occur a few weeks following the successful completion of antimicrobial therapy. | |||
==Diagnosis== | ==Diagnosis== | ||
===Symptoms=== | ===History and Symptoms=== | ||
In adults, a [[clinical prediction rule]] found the best [[medical sign|signs]] are<ref name="pmid8644759">{{cite journal |author=Katz DA, Lynch ME, Littenberg B |title=Clinical prediction rules to optimize cytotoxin testing for Clostridium difficile in hospitalized patients with diarrhea |journal=Am. J. Med. |volume=100 |issue=5 |pages=487–95 |year=1996 |pmid=8644759 |doi=10.1016/S0002-9343(95)00016-X }}</ref> significant [[diarrhea]] ("new onset of > 3 partially formed or watery stools per 24 hour period"), exposure of antibiotics, [[abdominal pain]], foul stool odor. | In adults, a [[clinical prediction rule]] found the best [[medical sign|signs]] are<ref name="pmid8644759">{{cite journal |author=Katz DA, Lynch ME, Littenberg B |title=Clinical prediction rules to optimize cytotoxin testing for Clostridium difficile in hospitalized patients with diarrhea |journal=Am. J. Med. |volume=100 |issue=5 |pages=487–95 |year=1996 |pmid=8644759 |doi=10.1016/S0002-9343(95)00016-X }}</ref> significant [[diarrhea]] ("new onset of > 3 partially formed or watery stools per 24 hour period"), exposure of antibiotics, [[abdominal pain]], foul stool odor. | ||
Revision as of 17:18, 24 April 2015
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C. difficile Infection Microchapters |
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Differentiating Clostridium difficile infectionfrom other Diseases |
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Diagnosis |
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Treatment |
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Clostridium difficile infection overview On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.
Overview
Historical Perspective
Clostridium difficile was first isolated in 1935 during an experiment from fecal extracts of healthy neonates. The association between C. difficile and antibiotic-associated pseudomembranous colitis was first made in 1978. In 2003, a resistant, hypervirulent strain of C. difficile (NAP/BI/027 strain) with increased synthesis of toxins A and B was first identified.
Pathophyusiology
Spores of C. difficile are transmitted via the fecal-oral route to the human host. Spore ingestion may be community-acquired (soil and food) or healthcare-associated (hospitals and clinics). Following ingestion, the acid-resistant spores of C. difficile are able to survive the human gastric acidity. C. difficile does not result in clinical manifestations in the majority of cases, whereby normal GI flora resists the growth of C. difficile, and the host immune responses adequately clear the infection before the development of clinical manifestations. However, in susceptible patients, C. difficile releases 2 major virulence factors: Exotoxins A and B (TcdA and TcdB), which act synergically and mediate adhesion to the colonic mucosa, luminal fluid accumulation, and development of pseudomembranous colitis. These toxins are able to glycosylate Rho GTPase (involved in actin cytoskeleton) and cause the formation of abnormal G-actin (leading to characteristic rounding of cells). Additionally, they stimulate macrophage-induced cytokine production and subsequent neutrophilic infiltration to the site of inflammation, which in part contributes to the disruption of the intestinal barrier and the development of clinical manifestations associated with the infection. On gross examination, colonic pseudomembranes with yellow colored plaque formation are typical. On microscopic examination, erosions within colonic crypts or formation of mushroom-like exudates with hemorrhage and necrosis are characteristic features.
Causes
C. difficile infection is caused by Clostridium difficile, a spore-forming, toxin-producing, oligate anaerobic, gram-positive bacillus.
Classification
C. difficile infection may be classified based on the clinical severity of the disease. The severity of the infection dictates the choice of antimicrobial therapy and the need for surgical consultation/management. Mild disease is defined as isolated diarrhea, whereas severe/complicated disease is defined as either delirium, shock, organ failure, high-grade fever, or marked leukocytosis.
Differential Diagnosis
Clostridium difficile infection must be differentiated from other diseases that cause acute inflammatory diarrhea, abdominal pain, fever, and ileus, including other causes of colitis (ischemic, collagenous, ulcerative), malabsorptive syndromes, diverticulitis, appendicitis, malignancies, drug-induced causes, and infections, such as salmonellosis, shigellosis, or gastrointestinal infections with Escherichia coli or Campylobacter jejuni.
Epidemiology and Demographics
The incidence of C. difficile infection is estimated to be 20 per 100,000 person-years. In USA, the majority (65%) of cases are associated with healthcare settings, and 25% of cases are associated with previous hospitalizations. Although patients of all age groups may develop C. difficile infection, elderly patients > 65 years may have up to eight-fold increased risk of developing C. difficile infection compared with younger patients. Whites and female patients are more predisposed to develop C. difficile infections. Although C. difficile is abundantly reported in Europe and the United States, the infection is a global burden.
Risk Factors
The most important risk factor for the development of C. difficile infection is antibiotic use. Although C. difficile infection has been described with almost all antibiotics, ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones are most classically and most commonly associated with development of C. difficile infection. Other important risk factors include recent hospitalization (< 12 weeks), advanced age (>65 years), immunodeficiency (primary or secondary causes), inflammatory bowel disease, and exposure to colonized/infected individuals. The association between gastric acid suppression and C. difficile infection has not been well established.
Natural History, Complications & Prognosis
Following ingestion of C. difficile spores, patients are colonized with the organism. Typically, young healthy individuals with adequate immune responses are able to clear the organism without development of any clinical manifestations. But patients with risk factors, such as recent antibiotic use, recent hospitalization, advanced age, or immunodeficiency, are at an increased risk of developing persistent colonization and/or developing signs and symptoms of the infection. The onset of clinical manifestations may occur within 2 hours up to several months of antibiotic use. Patients typically develop mild/moderate watery diarrhea (possibly bloody) associated with colicky diffuse abdominal pain, nausea, malaise, and fever. If left untreated, patients may develop colitis (with or without pseudomembrane formation). Approximately 3% of patients develop complications, which might be colonic (fulminant colitis) or extracolonic (small intestine invovelemtn, bacteremia, skin infections, reactive arthritis, abscess formation, empyema, or death). The majority of patients with C. difficile infection recover without sequelae and are responsive to antimicrobial therapy. Nonetheless, C. difficile is associated with a high lifetime recurrence rate that ranges between 20% to 70%, most of which occur a few weeks following the successful completion of antimicrobial therapy.
Diagnosis
History and Symptoms
In adults, a clinical prediction rule found the best signs are[1] significant diarrhea ("new onset of > 3 partially formed or watery stools per 24 hour period"), exposure of antibiotics, abdominal pain, foul stool odor.
The presence of any one of these findings has a sensitivity of 86% and a specificity of 45%.[1] In a study on hospitalized patients with a prevalence of positive cytotoxin assays of 14%, the positive predictive value was 20% and the negative predictive value was 95%.
Treatment
Medical Therapy
Many persons will also be asymptomatic and colonized with Clostridium difficile. Treatment in asymptomatic patients is controversial, also leading into the debate of clinical surveillance and how it intersects with public health policy.
It is possible that mild cases do not need treatment.[2]
Patients should be treated as soon as possible when the diagnosis of Clostridium difficile colitis (CDC) is made to avoid frank sepsis or bowel perforation. Treatment is by stopping any antibiotics and commencing specific anticlostridial antibiotics, e.g. metronidazole.
References
- ↑ 1.0 1.1 Katz DA, Lynch ME, Littenberg B (1996). "Clinical prediction rules to optimize cytotoxin testing for Clostridium difficile in hospitalized patients with diarrhea". Am. J. Med. 100 (5): 487–95. doi:10.1016/S0002-9343(95)00016-X. PMID 8644759.
- ↑ Nelson R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004610. PMID 17636768