|
|
| (43 intermediate revisions by 14 users not shown) |
| Line 1: |
Line 1: |
| __NOTOC__ | | __NOTOC__ |
| {{Taxobox | | {{Siren|Clostridium difficile infection}} |
| | color = lightgrey | | {{Clostridium difficile infection}} |
| | name = ''Clostridium difficile''
| | {{About1|Clostridium difficile}} |
| | image = Clostridium_difficile_01.jpg | | '''''For patient information, click [[Pseudomembranous colitis (patient information)|here]].'''''<br> |
| | image_caption = ''C. difficile'' colonies on a blood [[agar plate]].
| | {{CMG}}; {{AE}} {{YD}}; Abhishek Deshpande, M.D., Ph.D. |
| | regnum = [[Bacterium|Bacteria]]
| |
| | divisio = [[Firmicutes]]
| |
| | classis = [[Clostridia]]
| |
| | ordo = [[Clostridiales]]
| |
| | familia = [[Clostridiaceae]]
| |
| | genus = ''[[Clostridium]]''
| |
| | species = '''''C. difficile'''''
| |
| | binomial = ''Clostridium difficile''
| |
| | binomial_authority = Hall & O'Toole, 1935
| |
| }} | |
| {{Clostridium difficile}} | |
| {{CMG}}; '''Associate Editor(s)-in-Chief:''' [[User:Abhishek Deshpande|Abhishek Deshpande, M.D., PhD]] | |
|
| |
|
| {{SK}} C. Diff | | {{SK}} CDI; C. difficile; C. diff; C. diff infection; BI/NAP/027; CDAD; Hypervirulent ''Clostridium difficile'' |
|
| |
|
| ==Overview== | | ==[[Clostridium difficile infection overview|Overview]]== |
| '''''Clostridium difficile''''' or CDF/cdf' is a species of [[bacteria]] of the genus ''[[Clostridium]]'' which are [[Gram-positive]], [[Anaerobic organism|anaerobic]], [[endospore|spore]]-forming rods (bacillus).<ref name=Sherris>{{cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | pages = pp. 322-4 | publisher = McGraw Hill | year = 2004 | id = ISBN 0-8385-8529-9 }}</ref> ''Clostridium difficile'' (C. diff) is one of the most common hospital-acquired infections, particularly in elderly hospitalized patients, and also one of the most common complications of antibiotics in hospitalized patients. Patients are rarely infected unless the normal flora of the intestinal tract has been altered by antibiotics. Up to 10% of patients hospitalized >2 days are affected.Of note, most antibiotic-associated diarrhea is not due to ''C. diff'', but is due to an osmotic type diarrhea. The antibiotics wipe out the gastrointestinal (GI) tract’s normal flora, which usually break down unabsorbed carbohydrates. These unabsorbed carbohydrates remain in the lumen and carry with them water, resulting in diarrhea.''C. difficile'' is the most significant cause of [[pseudomembranous colitis]],<ref name=eMed1942>{{ cite web | url= http://www.emedicine.com/med/topic1942.htm#section~introduction
| |
| | title=Pseudomembranous Colitis
| |
| | work=eMedicine
| |
| | date=1 July 2005
| |
| | publisher=WebMD
| |
| | accessdate=2007-01-11}} </ref> a severe infection of the [[colon (anatomy)|colon]], often after normal [[gut flora]] is eradicated by the use of [[antibiotic]]s. Treatment is by stopping any antibiotics and commencing specific anticlostridial antibiotics, e.g. [[metronidazole]].
| |
|
| |
|
| == Pathophysiology & Etiology== | | ==[[Clostridium difficile infection historical perspective|Historical Perspective]]== |
|
| |
|
| ===Bacteriology=== | | ==[[Clostridium difficile infection pathophysiology|Pathophysiology]]== |
| Clostridia are motile [[bacterium|bacteria]] that are ubiquitous in nature and are especially prevalent in soil. Under the microscope after [[Gram stain]]ing, they appear as long drumsticks with a bulge located at their terminal ends. ''Clostridium difficile'' cells are [[Gram positive]]. ''Clostridium'' shows optimum growth when plated on [[blood agar]] at human body temperatures. When the environment becomes stressed, however, the bacteria produce spores that tolerate the extreme conditions that the active bacteria cannot. First described by Hall and O'Toole in 1935, "the difficult clostridium" was resistant to early attempts at isolation and grew very slowly in culture.<ref name=Hall_1935>{{cite journal | author = Hall I, O'Toole E | title = Intestinal flora in newborn infants with a description of a new pathogenic anaerobe, ''Bacillus difficilis'' | journal = Am J Dis Child | year = 1935 | volume = 49 | issue = | pages = 390 | url= }}</ref>
| |
| ''C. difficile'' is a commensal bacterium of the human [[intestine]] in a minority of the population. . In small numbers it does not result in disease of any significance. Antibiotics, especially those with a broad spectrum of activity, cause disruption of normal [[intestinal flora]], leading to an overgrowth of ''C. difficile''. This leads to [[pseudomembranous colitis]].
| |
|
| |
|
| ''C. difficile'' is resistant to most [[antibiotic]]s. It flourishes under these conditions. It is transmitted from person to person by the [[fecal-oral route]]. Because the organism forms heat-resistant spores, it can remain in the [[hospital]] or [[nursing home]] environment for long periods of time. It can be cultured from almost any surface in the hospital. Once spores are ingested, they pass through the stomach unscathed because of their acid-resistance. They change to their active form in the colon and multiply. It has been observed that several [[disinfectant]]s commonly used in hospitals may fail to kill the bacteria, and may actually promote spore formation. However, disinfectants containing [[bleach]] are effective in killing the organisms<ref>{{cite news | url= http://news.bbc.co.uk/1/hi/health/4871840.stm
| | ==[[Clostridium difficile infection causes|Causes]]== |
| | title=Cleaning agents 'make bug strong'
| |
| | work=BBC News Online
| |
| | date=3 April 2006
| |
| | accessdate=2007-01-11}}</ref>.
| |
|
| |
|
| Patients are rarely infected unless the normal flora of the intestinal tract has been altered by [[antibiotic]]s. Following colonization ''C. diff'' releases two [[cytotoxin]]s, A and B:
| | ==[[Clostridium difficile infection classification|Classification]] == |
| * The cytotoxins bind to receptors on intestinal [[epithelial cell]]s.
| |
| * The cytotoxins usually result in acute inflammatory infiltrate, leading to cell [[necrosis]] and shedding.
| |
| * A shallow [[ulcer]] results, from which serum proteins, mucus, and inflammatory cells emanate, leading to the appearance of a pseudomembrane.
| |
| * Some strains do not produce toxin.
| |
|
| |
|
| === Toxins === | | ==[[Clostridium difficile infection differential diagnosis|Differentiating Clostridium difficile from other Diseases]]== |
|
| |
|
| Pathogenic ''C. difficile'' strains produce various [[toxin]]s. The most well-characterized are [[enterotoxin]] (''toxin A'') and [[cytotoxin]] (''toxin B'').<ref name=Sherris /> These two toxins are both responsible for the [[diarrhea]] and [[inflammation]] seen in infected patients, although their relative contributions have been debated by researchers. Another toxin, ''binary toxin'', has also been described, but its role in disease is not yet fully understood.<ref>{{cite journal |author=Barth H, Aktories K, Popoff M, Stiles B |title=Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins |journal=Microbiol Mol Biol Rev |volume=68 |issue=3 |pages=373-402, table of contents |year=2004 |pmid=15353562}}</ref>
| | ==[[Clostridium difficile infection epidemiology and demographics|Epidemiology and Demographics]]== |
| ===Role in disease ===
| |
|
| |
|
| With the introduction of [[broad-spectrum antibiotics]] in the latter half of the twentieth century, antibiotic-associated diarrhea became more common. [[Pseudomembranous colitis]] was first described as a complication of ''C. difficile'' [[infection]] in 1978,<ref name=Larson_1978>{{cite journal |author=Larson H, Price A, Honour P, Borriello S |title=''Clostridium difficile'' and the aetiology of pseudomembranous colitis |journal=Lancet |volume=1 |issue=8073 |pages=1063-6 |year=1978 |pmid=77366}}</ref> when a toxin was isolated from patients suffering from pseudomembranous colitis and [[Koch's postulates]] were met.
| | ==[[Clostridium difficile infection risk factors|Risk Factors]]== |
|
| |
|
| ''Clostridium Difficile Infection'' (CDI), can range in severity from asymptomatic to severe and life threatening, and many deaths have been reported, especially amongst the aged. People are most often infected in [[hospital]]s, [[nursing home]]s, or institutions, although ''C. difficile'' infection in the community, outpatient setting is increasing. ''Clostridium difficile'' associated diarrhea (aka CDAD) has been linked to use of broad-spectrum antibiotics such as [[cephalosporin]]s and [[clindamycin]], though the use of quinolones is now probably the most likely culprit, which are frequently used in hospital settings. Frequency and severity of ''C. difficile'' colitis remains high and seems to be associated with increased death rates. Immunocompromised status and delayed diagnosis appear to result in elevated risk of death. Early intervention and aggressive management are key factors to recovery.
| | ==[[Clostridium difficile infection natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
|
| |
|
| The rate of ''Clostridium difficile'' acquisition is estimated to be 13 percent in patients with hospital stays of up to two weeks and 50 percent in those with hospital stays longer than four weeks.
| | ==Diagnosis== |
|
| |
|
| Increasing rates of community-acquired ''Clostridium difficile''-associated infection/disease (CDAD) has also been linked to the use of medication to suppress [[gastric acid]] production: [[H2-receptor antagonist]]s increased the risk twofold, and [[proton pump inhibitor]]s threefold, mainly in the elderly. It is presumed that increased gastric [[pH]], (alkalinity), leads to decreased destruction of spores.<ref name=Dial_2005>{{cite journal |author=Dial S, Delaney J, Barkun A, Suissa S |title=Use of gastric acid-suppressive agents and the risk of community-acquired ''Clostridium difficile''-associated disease |journal=[[Journal of the American Medical Association|JAMA]] |volume=294 |issue=23 |pages=2989-95 |year=2005 |pmid=16414946}}</ref>
| | [[Clostridium difficile infection history and symptoms|History and Symptoms]] | [[Clostridium difficile infection physical examination|Physical Examination]] | [[Clostridium difficile infection laboratory findings|Laboratory Findings]] | [[Clostridium difficile infection abdominal x ray|Abdominal X Ray]] | [[Clostridium difficile infection abdominal CT scan|Abdominal CT Scan]] | [[Clostridium difficile infection other imaging findings|Other Imaging Findings]] | [[Clostridium difficile infection biopsy|Biopsy]] |
| | |
| == Genetics ==
| |
| On December 14, 2005, researchers at McGill University in Montreal, Quebec, led by Dr. Ken Dewar and Dr. Andre Dascal and in collaboration with province-organized NPO Genome Quebec's research facility, announced they had cracked the genetic code of the highly virulent Quebec strain of ''C. difficile''. This was accomplished by using ultra high-throughput sequencing technology. The tests involved doing 400,000 DNA parallel sequencing reactions which took the bacterium's genome apart and reassembled it so it could be studied.<ref name=Loo_2005 /><ref>[http://www.iapm.ca/newsmanager/anmviewer.asp?a=144&z=14 Scientists map C. difficile strain] - Institute of Public Affairs, Montreal</ref>
| |
| | |
| It is expected this will allow quicker detection of the disease and better treatment.
| |
| | |
| ==Risk Factors==
| |
| * Most antibiotics, including metronidazole, can be associated with ''C. diff'' infection, though the most commonly implicated are ampicillin, clindamycin, and the cephalosporins. Antibiotics only rarely associated with infection include parenteral antibiotics, tetracyclines, chloramphenicol, metronidazole and vancomycin. Onset is usually during or shortly after a course of antibiotics.
| |
| * Patients who have been staying long-term in a hospital or a nursing home have a higher likelihood of being [[Colony (biology)|colonized]] by this bacterium. Hospitalized patients are more likely to infected if their roommates are infected. ''C. diff'' can be cultured from many surfaces in the hospital room, and spores have been identified everywhere, including toilets, floors, mops, scales, furniture, etc. Health care workers commonly carry the organism on their hands, clothing and stethoscopes, though they are not usually fecal carriers.
| |
| * Hospital outbreaks are common.
| |
| * Newborns are often infected, but are asymptomatic. By 24 months of age, over half of toddlers have immunoglobulins to toxins A and B.
| |
| | |
| == Diagnosis ==
| |
| Often clinicians begin treatment before results have come back based on clinical presentation to prevent complications. Knowledge of the local epidemiology of intestinal flora of a particular institution can guide therapy.
| |
| | |
| 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
| |
| | |
| The presence of any one of these findings has a [[sensitivity (tests)|sensitivity]] of 86% and a [[specificity (tests)|specificity]] of 45%.<ref name="pmid8644759"/> In this study of hospitalized patients with a prevalence of positive cytotoxin assays of 14%, the [[positive predictive value]] was 20% and the [[negative predictive value]] was 95%.
| |
| | |
| ===History and Symptoms===
| |
| Clinical manifestations can be quite variable. Some patients are asymptomatic, and others can present critically ill with [[toxic megacolon]].
| |
| * Up to 2/3 of infected hospitalized patients are asymptomatic, but shed organisms and contaminate their environment. These patients are called ''C. Diff'' fecal excretors. These patients can be treated with [[vancomycin]] or metronidazole, but the bug is often not eradicated in these patients.
| |
| * The reason for the variability is not clear and is not accounted for by strain differences. Host factors are probably important, such as the presence of antitoxin antibodies and colonic toxin receptors.
| |
| * Risk factors for severe [[colitis]] include malignancy, [[Chronic Obstructive Pulmonary Disease]] (COPD), [[immunosuppression]], [[renal failure]], exposure to anti-peristaltic meds and [[clindamycin]].
| |
| * Onset is usually during or shortly after a course of antibiotics. Cases rarely occur even a month after a course of antibiotics. Rarely patients have no recent history of antibiotics.
| |
| | |
| '''Antibiotic-associated diarrhea with ''C. diff'' infection, but without colitis'''
| |
| * Acute, foul-smelling watery [[diarrhea]], with a mean of 3-4 stools a day.
| |
| * Lower [[abdominal pain]], sometimes crampy
| |
| * Low-grade [[fever]]
| |
| | |
| '''Antibiotic-associated diarrhea with C. diff infection with colitis''', but without pseudomembrane development
| |
| In addition to profuse, watery diarrhea of 5-15 bowel movements daily, the patients suffer from:
| |
| * [[Fever]]
| |
| * [[Malaise]]
| |
| * [[Anorexia]]
| |
| * Lower quadrant [[abdominal pain]] and cramps, relieved by the passage of diarrhea.
| |
| * [[Nausea]]
| |
| * [[Dehydration]]
| |
| * [[Leucocytosis]]
| |
| * Fecal [[leucocytes]] present in >50%. Occult [[bleeding]] not uncommon.
| |
| * [[Sigmoidoscopy]] shows a nonspecific diffuse or patchy erthrematous [[colitis]] without pseudomembranes.
| |
| | |
| '''Antibiotic-associated diarrhea with ''C. diff'' infection with colitis and pseudomembrane development'''
| |
| Patients tend to have the prominent signs as symptoms described above.
| |
| * Rarely patients will develop indolent, subacute [[pseudomembranous colitis]] with a protein-losing state due to the diffuse [[pancolitis]]. Patients may have severe [[hypoalbuminemia]], [[ascites]], peripheral [[edema]], and their only signs/symptoms may be low-grade [[fever]], [[anorexia]] and [[abdominal discomfort]].
| |
| * [[Sigmoidoscopy]] shows pseudomembranes; raised yellow or off-white plaques ranging up to 1 cm in diameter scattered over the colorectal mucosa.
| |
| *:* Occasionally pseudomembranes will be located in the proximal colon.
| |
| | |
| '''Fulminant colitis'''<br>
| |
| Fulminant [[colitis]] is an uncommon complication that occurs in 2-3% of patients with ''C. Diff'', and can results in perforation, prolonged [[ileus]], [[megacolon]], and [[death]].
| |
| Patients may present with:
| |
| * Severe [[abdominal pain]] and distension
| |
| * Severe [[diarrhea]]; diarrhea may be absent in patients with ileus
| |
| * [[Fever]], [[chills]]
| |
| * [[Lethargy]]
| |
| * [[Tachycardia]]
| |
| * [[Leucocytosis]], up to 40,000 mm3
| |
| * [[Metabolic acidosis]]
| |
| | |
| '''Toxic megcolon''' is an enlarged, dilated colon >7cm associated severe systemic toxicity.
| |
| * Small intestinal dilation may also occur
| |
| * Air-fluid levels may be present
| |
| * Submucosal [[edema]] may result in thumb-printing
| |
| | |
| ==Laboratory Findings==
| |
| ===Cytotoxicity assay===
| |
| ''C. difficile'' toxin detection as cytopathic effect in cell culture, and neutralized with specific anti-sera is the practical gold standard for studies investigating new CDAD diagnostic techniques. Toxigenic culture, in which organisms are cultured on selective medium and tested for toxin production remains the [[Gold standard (test)|gold standard]] and is the most sensitive and specific test, although it is slow and labour-intensive.<ref name=Murray_1993>{{cite book | author = Murray PR, Baron EJ, Pfaller EA, Tenover F, Yolken RH (editors) |title = Manual of Clinical Microbiology | edition = 8th ed | publisher=ASM Press | location = Washington DC | date = 2003 | isbn = 1-55581-255-3}}</ref>
| |
| | |
| ===Enzyme-linked immunoabsorbant assay (ELISA) for toxin===
| |
| Assessment of the A and B toxins by [[ELISA|enzyme-linked immunoabsorbant assay]] (ELISA) for toxin A or B (or both) has:
| |
| * [[sensitivity (tests)|sensitivity]] 63-99%
| |
| * [[specificity (tests)|specificity]] 93-100%
| |
| | |
| At a prevalence of 15%, this leads to:
| |
| * [[positive predictive value]] 73%
| |
| * [[negative predictive value]] 96%
| |
| | |
| <!-- 20% prev is both prior abys and sig diarrhea per pred rule above -->
| |
| Experts recommend sending as many as three samples to rule-out disease if initial tests are negative. ''C. difficile'' toxin should clear from the stool of previously infected patients if treatment is effective.
| |
| | |
| Unfortunately, many hospitals only test for the prevalent toxin A. Strains that express only the B toxin are now present in many hospitals and ordering both toxins should occur. Not testing for both may contribute to a delay in obtaining laboratory results, which is often the cause of prolonged illness and poor outcomes.
| |
| | |
| ===Other stool tests===
| |
| Stool [[leukocyte]] measurements and stool [[lactoferrin]] levels have also been proposed as diagnostic tests, but may have limited diagnostic accuracy.<ref name=Vaishnavi_2000>{{cite journal |author=Vaishnavi C, Bhasin D, Kochhar R, Singh K |title=Clostridium difficile toxin and faecal lactoferrin assays in adult patients |journal=Microbes Infect |volume=2 |issue=15 |pages=1827-30 |year=2000 |pmid=11165926}}</ref>
| |
| | |
| ===Computed tomography===
| |
| In a recent study, a patient who received a diagnosis of CDC on the basis of [[computed tomography]] (CT scan) had an 88% probability of testing positive on stool assay.<ref name="pmid11222194">{{cite journal |author=Kirkpatrick ID, Greenberg HM |title=Evaluating the CT diagnosis of Clostridium difficile colitis: should CT guide therapy? |journal=AJR. American journal of roentgenology |volume=176 |issue=3 |pages=635–9 |year=2001 |pmid=11222194 |doi=|url=http://www.ajronline.org/cgi/content/full/176/3/635}}</ref> Wall thickening is the key CT finding in this disease. Once colon wall thickening is identified as being >4 mm, the best ancillary findings were:
| |
| * pericolonic stranding
| |
| * [[ascites]]
| |
| * colon wall nodularity
| |
| The presence of wall thickness plus any one of these ancillary findings yields:
| |
| * [[sensitivity (tests)|sensitivity]] of 70%
| |
| * [[specificity (tests)|specificity]] of 93%
| |
| | |
| Using criteria of >=10 mm or a wall thickness of >4 mm and any of the more-specific findings does not add significantly to the diagnosis but gives equally satisfactory results. In this study with a prevalence of positive ''C. difficile'' toxin of 54%, the [[positive predictive value]] was 88%. Patients who have antibiotic-associated diarrhea who have CT findings diagnostic of CDC merit consideration for treatment on that basis. A weakness of this study was not using a [[Gold standard (test)|gold standard]] [[cytotoxicity]] assay.
| |
| | |
| ===Endoscopy===
| |
| Endoscopy may be indicated for quick diagnosis of [[pseudomembranous colitis]] or in atypical cases.
| |
|
| |
|
| ==Treatment== | | ==Treatment== |
| 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.<ref name="pmid17636768">Nelson R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004610. PMID 17636768</ref>
| |
|
| |
| 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.
| |
|
| |
| === Pharmacotherapy ===
| |
| Three antibiotics are effective against ''C. difficile''.
| |
| *[[Metronidazole]] 500mg orally three times daily is the drug of choice, because of superior tolerability, lower price and comparable efficacy<ref name="pmid6138597">Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ, Lee JT Jr. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983 Nov 5;2(8358):1043-6. PMID 6138597</ref>. Metronidazole is taken up by the GI tract, unlike vancomycin. Some therefore recommend prescriptions of severe cases with vancomycin, to insure adequate levels. IV metronidazole 500 mg TID is also effective.
| |
| *Oral [[vancomycin]] 125 mg four times daily is second-line therapy, but is avoided due to theoretical concerns of converting intestinal flora into vancomycin resistant organisms. However, it is used in the following cases: severe ''C. difficile'' diarrhea<ref name="pmid17599306">{{cite journal |author=Zar FA, Bakkanagari SR, Moorthi KM, Davis MB |title=A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity |journal=Clin. Infect. Dis. |volume=45 |issue=3 |pages=302–7 |year=2007 |pmid=17599306 |doi=10.1086/519265}}</ref> (the duration of diarrhea is reduced to 3 versus 4.6 days with metronidazole; no response to oral metronidazole; the organism is resistant to metronidazole; the patient is allergic to metronidazole; the patient is either pregnant or younger than 10 years of age. Vancomycin must be administered orally because IV administration does not achieve gut lumen minimum therapeutic concentration.
| |
| *The use of [[linezolid]] may be considered too.
| |
|
| |
| It has been known that drugs traditionally used to stop diarrhea worsen the course of ''C. difficile''-related pseudomembranous colitis. [[Loperamide]], [[diphenoxylate]] and [[bismuth]] compounds are indeed contraindicated, because slowing of fecal transit time is thought to result in extended toxin-associated damage. [[Cholestyramine]], a powder drink occasionally used to lower cholesterol, is effective in binding both Toxin A and B, and slows bowel motility and helps prevent dehydration.<ref name=Stroehlein_2004>{{cite journal |author=Stroehlein J |title=Treatment of ''Clostridium difficile'' Infection |journal=Curr Treat Options Gastroenterol |volume=7 |issue=3 |pages=235-239 |year=2004 |pmid=15149585}}</ref> The dosage can be 4 grams daily, to up to four doses a day: caution should be exercised to prevent constipation, or drug interactions, most notably the binding of drugs by cholestyramine, preventing their absorption. A last-resort treatment in [[immunosuppression|immunosuppressed]] patients is [[intravenous immunoglobulin]] (IVIG).<ref name=Stroehlein_2004 />
| |
|
| |
| [[Pseudomembranous colitis]] caused by ''C. difficile'' is treated with antibiotics, for example, [[vancomycin]], [[metronidazole]], bacitracin or fusidic acid.
| |
|
| |
| Patients should be treated for 10-14 days, unless the inciting antibiotics can’t be discontinued, in which case metronidazole or vancomycin should be continued for a week or so after discontinuation of the inciting antibiotics.
| |
| Failure to initially respond is typically not due to resistance, but may be due to misdiagnosis, noncompliance or other GI disease.
| |
|
| |
| Up to 15-20% of patients will [[relapse]] after treatment, not typically due to resistant organisms. The exact mechanism has not been clarified; these patients often do not develop as prominent an antibody response, so immune mediated defects may be contributory. Relapse usually is within a few days of discontinued prescription, though may be as long as 30 days afterward. For relapse, patients should receive a second course of metronidazole for 14 days. For a second relapse, a ''C. diff'' titer should be checked to confirm the diagnosis, and then a third course of antibiotics should be with vancomycin. For patients with multiple relapses, some recommend a schedule of tapering vancomycin, from full dose down to 125 mg q3 days over the course of 6 weeks. Other potential prescriptions that are not commonly used include prescriptions with [[cholestyramine]], which binds the toxin (but will also bind vancomycin), and attempts to repopulate the gut with organisms.
| |
|
| |
| ===Fecal bacteriotherapy===
| |
| [[Fecal bacteriotherapy]], a procedure related to probiotic research, has been suggested as a potential cure for the disease. It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to reverse bacterial imbalance responsible for the recurring nature of the infection. It has a success rate of nearly 95% according to some sources.<ref name=Schwan_1983>{{cite journal | author = Schwan A, Sjölin S, Trottestam U, Aronsson B | title = Relapsing clostridium difficile enterocolitis cured by rectal infusion of homologous faeces. | journal = Lancet | volume = 2 | issue = 8354 | pages = 845 | year = 1983 | id = PMID 6137662}}</ref><ref name=Schwan_1994>{{cite journal | author = Paterson D, Iredell J, Whitby M | title = Putting back the bugs: bacterial treatment relieves chronic diarrhoea. | journal = Med J Aust | volume = 160 | issue = 4 | pages = 232-3 | year = 1994 | id = PMID 8309401}}</ref><ref name=Borody_2000>{{cite journal | author = Borody T | title = "Flora Power"-- fecal bacteria cure chronic C. difficile diarrhea. | journal = Am J Gastroenterol | volume = 95 | issue = 11 | pages = 3028-9 | year = 2000 | url = http://www.cdd.com.au/pdf/paper32.pdf | id = PMID 11095314}}</ref>
| |
|
| |
| == Surgery and Device Based Therapy ==
| |
| Patients with signs/symptoms of fulminant colitits should be evaluated by surgery for possible urgent surgery for [[bowel perforation]], impending perforation, severe ileus with megacolon, or refractory [[septicemia]].
| |
|
| |
| === Indications for Surgery ===
| |
| Indications for surgery include:
| |
| * Peritoneal signs
| |
| * Persistent [[bacteremia]]
| |
| * Progressive disease
| |
| * CT showing pericolonic inflammation with increasing bowel wall edema.
| |
|
| |
| ===Colectomy===
| |
| In those patients that develop systemic symptoms of CDC, colectomy may improve the outcome if performed before the need for [[vasopressor]]s. The usual intervention is a subtotal colectomy with [[ileostomy]].
| |
|
| |
| === Recurrence ===
| |
| The evolution of protocols for patients with recurrent ''C. difficile'' diarrhea also present a challenge: there is no known proper length of time or universally accepted alternative drugs with which one should be treated. However, re-treatment with [[metronidazole]] or [[vancomycin]] at the previous dose for 10 to 14 days is generally successful. The addition of [[rifampin]] to vancomycin also has been effective. Prophylaxis with competing, nonpathogenic organisms such as ''[[Lactobacillus]]'' spp. or ''[[Saccharomyces boulardii]]'' has been found to be helpful in preventing relapse in small numbers of patients (see, for example, [[Florastor]], or [[Lactinex]]). It is thought that these organisms, also known as [[probiotics]], help to restore the natural flora in the gut and make patients more resistant to colonization by ''C. difficile''.
| |
|
| |
| ==Prevention==
| |
| The most effective method for preventing ''Clostridium difficile associated diarrhea'' (CDAD) is proper antimicrobial prescribing. In the hospital setting, where CDAD is most common, nearly all patients who develop CDAD are exposed to antimicrobials. Although this sounds easy to do, approximately 50% of antimicrobial use is considered inappropriate. This is consistent whether in the hospital, clinic, community, or academic setting. Several studies have demonstrated a decrease in CDAD by limiting antibitoics most strongly associated with CDAD or by limiting unnecessary antimicrobial prescribing in general, both in outbreak and non-outbreak settings.
| |
|
| |
| Infection control measures, such as wearing gloves when caring for patients with CDAD, have been proven to be effective at preventing CDAD. This works by limiting the spread of ''C. difficile'' in the hospital setting.
| |
|
| |
| Treatment with various oral supplements containing live bacteria has been studied in efforts to prevent ''Clostridium difficile''-associated infection/disease. A [[randomized controlled trial]] using a probiotic drink containing ''Lactobacillus casei'', ''L bulgaricus'', and ''Streptococcus thermophilus'' was reported to have some efficacy. This study was sponsored by the company that produces the drink studied <ref name="pmid17604300">{{cite journal |author=Hickson M, D'Souza AL, Muthu N, ''et al'' |title=Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial |journal=BMJ |volume=335 |issue=7610 |pages=80 |year=2007 |pmid=17604300 |doi=10.1136/bmj.39231.599815.55}}</ref>. Although intriguing, several other studies have been unable to demonstrate any benefit of oral supplements of similar bacteria at preventing CDAD. Of note, patients on the antibiotics most strongly associated with CDAD were excluded from this study.
| |
|
| |
| == Notable outbreaks ==
| |
| On June 4, 2004, two outbreaks of a highly virulent strain of this bacterium were reported in Montreal, Quebec and Calgary, Alberta, in Canada. Sources put the death count as low as 36 and as high as 89, with approximately 1,400 cases in 2003 and within the first few months of 2004. ''C. difficile'' infections continued to be a problem in the Quebec health care system in late 2004. As of March 2005, it had spread into the Toronto, Ontario area, hospitalizing 10 people. One died while the others were being discharged.
| |
|
| |
| A similar outbreak took place at Stoke Mandeville Hospital in the United Kingdom between 2003 and 2005. The local [[epidemiology]] of ''C. difficile'' may offer clues on how its spread may relate to the amount of time a patient spends in hospital and/or a rehabilitation center. It also samples institutions' ability to detect increased rates, and their capacity to respond with more aggressive hand washing campaigns, quarantine methods, and availability of yoghurt to patients at risk for infection.
| |
|
| |
| It has been suggested that both the Canadian and English outbreaks were related to the seemingly more virulent 027 strain of bacterium. This strain has also been implicated in an epidemic at two Dutch hospitals (Harderwijk and Amersfoort, both 2005). A theory for explaining the increased virulence of 027 is that it is a hyperproducer of both toxin A and B, and that certain antibiotics may actually stimulate the bacteria to hyperproduce.
| |
|
| |
| On December 2, 2005, The New England Journal of Medicine, in an article spearheaded by Drs. Vivian Loo, Louise Poirier, and Mark Miller, reported the emergence of a new, highly toxic strain of ''C. difficile'', resistant to [[fluoroquinolone]] antibiotics, such as [[Cipro]] (ciprofloxacin) and [[Levaquin]] (levofloxacin), said to be causing geographically dispersed outbreaks in North America.<ref name=Loo_2005>{{cite journal |author=Loo V, Poirier L, Miller M, Oughton M, Libman M, Michaud S, Bourgault A, Nguyen T, Frenette C, Kelly M, Vibien A, Brassard P, Fenn S, Dewar K, Hudson T, Horn R, René P, Monczak Y, Dascal A |title=A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality |journal=N Engl J Med |volume=353 |issue=23 |pages=2442-9 |year=2005 |pmid=16322602}}</ref> The [[Centers for Disease Control]] in Atlanta has also warned of the emergence of an epidemic strain with increased virulence, antibiotic resistance, or both.<ref name=McDonald_2005>{{cite journal |author=McDonald L |title=''Clostridium difficile'': responding to a new threat from an old enemy |journal=Infect Control Hosp Epidemiol |volume=26 |issue=8 |pages=672-5 |year=2005 |url= http://www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_ICHE08_05.pdf | pmid=16156321}}</ref>
| |
|
| |
| As one analyzes the pool of patients with the spores, many who are asymptomatic will pass the organism to individuals who are immunocompromised and hence, susceptible to increasing rates of diarrhea and poor outcome. It seems notable that the clusters described above represent a challenge to epidemiologists trying to understand how the illness spreads via the convergence of information technology with clinical surveillance.
| |
|
| |
| On October 1, 2006, the bacteria was said to have killed at least 49 people at hospitals in Leicester, England over eight months, according to a National Health Service investigation. Another 29 similar cases were investigated by [[coroner]]s.<ref>[http://news.bbc.co.uk/1/hi/england/leicestershire/5396800.stm Trust confirms 49 superbug deaths] - [[BBC News]]</ref> A UK Department of Health memo leaked shortly afterwards revealed significant concern in government about the bacterium, described as being "endemic throughout the health service"<ref>{{cite web| url= http://www.timesonline.co.uk/article/0,,2-2541472,00.html| title=Leaked memo reveals that targets to beat MRSA will not be met| author=Nigel Hawkes| date=11th January 2007| work=The Times| accessdate = 2007-01-11}}</ref>
| |
|
| |
| On October 27, 2006, the bacteria was attributed to 9 deaths in Quebec, Canada.<ref>{{cite web| url= http://cnews.canoe.ca/CNEWS/Canada/2006/10/27/2145519.html| title=C. difficile blamed for 9 death in hospital near Montreal| date=11th January 200| work=cNews| accessdate = 2007-01-11}}</ref>
| |
|
| |
| On November 18th, 2006, the bacteria was reported to have been responsible for 12 deaths in Quebec, Canada. This 12th reported death was only two days after the St. Hyacinthe's Honoré Mercier announced that the outbreak was under control. 31 patients were diagnosed with Clostridium difficile and four (as of Sat. Nov 18th) were still under observation. Cleaning crews took measures in an attempt to clear the outbreak.<ref>[http://www.cbc.ca/canada/story/2006/11/18/difficile-outbreak.html 12th person dies of C. difficile at Quebec hospital] - [[CBC News]]</ref>
| |
|
| |
| On February 27, 2007, a new outbreak was identified at Trillium Health Centre in Mississauga Ontario, where 14 people were diagnosed with the bacteria. The bacteria was the same strain as the one in Quebec. Officials have not been able to determine if C. difficile was responsible for deaths of four patients over the prior two months.<ref>[http://toronto.ctv.ca/servlet/an/local/CTVNews/20070228/cdifficile_mississauga_outbreak_070228/20070228/?hub=TorontoHome]</ref>
| |
|
| |
| In October 2007, Maidstone and Tunbridge Wells NHS Trust was heavily criticized by the Healthcare Commission regarding its handling of a major outbreak of ''C. difficile'' in its hospitals in Kent from April 2004 to September 2006. In its report, the Commission estimated that about 90 patients "definitely or probably" died as a result of the infection. <ref>Healthcare Commission press release: [http://www.healthcarecommission.org.uk/newsandevents/pressreleases.cfm/cit_id/5875/FAArea1/customWidgets.content_view_1/usecache/false Healthcare watchdog finds significant failings in infection control at Maidstone and Tunbridge Wells NHS Trust], 11 October 2007</ref><ref>Daily Telegraph, [http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2007/10/11/ncdiff611.xml Health Secretary intervenes in superbug row], 11 October 2007</ref>
| |
|
| |
| ==References==
| |
| <!-- ---------------------------------------------------------------
| |
| See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for a
| |
| discussion of different citation methods and how to generate
| |
| footnotes using the <ref> & </ref> tags and the {{Reflist}} template
| |
| -------------------------------------------------------------------- -->
| |
| {{Reflist|2}}
| |
|
| |
| The content on this page was first contributed by: Ellison L. Smith, M.D.
| |
|
| |
| === Further reading ===
| |
|
| |
| * {{cite journal |author=Dallal R, Harbrecht B, Boujoukas A, Sirio C, Farkas L, Lee K, Simmons R |title=Fulminant ''Clostridium difficile'': an underappreciated and increasing cause of death and complications |journal=Ann Surg |volume=235 |issue=3 |pages=363-72 |year=2002 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11882758 |pmid=11882758}}
| |
|
| |
| * {{cite book | author = Martin S, Jung R | title = Gastrointestinal infections and enterotoxigenic poisonings. In: Pharmacotherapy: A Pathophysiologic Approach (DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors). | pages = pp. 2042-2043 | edition = 6th ed. | publisher = McGraw-Hill | year = 2005 | id = ISBN }}
| |
|
| |
| * {{cite journal |author=McDonald L, Killgore G, Thompson A, Owens R, Kazakova S, Sambol S, Johnson S, Gerding D |title=An epidemic, toxin gene-variant strain of ''Clostridium difficile'' |journal=N Engl J Med |volume=353 |issue=23 |pages=2433-41 |year=2005 |pmid=16322603}}
| |
|
| |
| * {{cite book | author = Yamada T; Alpers DH (editors) | title = Textbook of Gastroenterology | edition = 4th ed. | pages = pp. 1870-1875 | publisher = Lippincott Williams & Wilkins | year = 2003 | id = ISBN 0-7817-2861-4 }}
| |
|
| |
| * {{cite journal |author=van den Hof S, van der Kooi T, van den Berg R, Kuijper E, Notermans D |title=''Clostridium difficile'' PCR ribotype 027 outbreaks in the Netherlands: recent surveillance data indicate that outbreaks are not easily controlled but interhospital transmission is limited |journal=Euro Surveill |volume=11 |issue=1 |pages=E060126.2 |year=2006 |url=http://www.eurosurveillance.org/ew/2006/060126.asp#2 | pmid=16801713}}
| |
|
| |
| * {{cite journal |author=Sunenshine R, McDonald L | title = ''Clostridium difficile-associated disease: New challenges from an established pathogen''| journal=Cleveland Clinic J. Med. |volume=73 |pages=187 |year=2006}}
| |
|
| |
|
| ==External links==
| | [[Clostridium difficile infection medical therapy|Medical Therapy]] | [[Clostridium difficile infection surgery|Surgery]] | [[Clostridium difficile infection prevention|Prevention]] | [[Clostridium difficile infection cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Clostridium difficile infection future or investigational therapies|Future or Investigational Therapies]] |
| * [http://www.cdiff-support.co.uk ''UK Clostridium difficile'' Support Group]
| |
| * [http://www.cdiffsupport.com ''Clostridium difficile'' Support Group]
| |
| * [http://www.economist.com/science/displaystory.cfm?story_id=6971098 "From hand to mouth"] Article from The Economist discussing ''C. difficile'' (requires subscription)
| |
| * [http://pathema.tigr.org/tigr-scripts/Clostridium/PathemaHomePage.cgi Pathema-''Clostridium'' Resource]
| |
| * [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5447a1.htm US CDC Report on Severe ''Clostridium difficile''--Associated Disease in Populations Previously at Low Risk--Four States, 2005]
| |
|
| |
|
| | ==Case Studies== |
|
| |
|
| [[es:Clostridium difficile]] | | [[Clostridium difficile infection case study one|Case #1]] |
| [[fr:Clostridium difficile]]
| |
|
| |
|
| | ==External Links== |
|
| |
|
| {{WikiDoc Help Menu}}
| | [http://www.cdc.gov/HAI/pdfs/cdiff/Cdiff_tagged.pdf CDC FAQs about ''Clostridium difficile'' infection] |
| {{WikiDoc Sources}}
| |
|
| |
|
| | [[Category:Bacterial diseases]] |
| [[Category:Disease]] | | [[Category:Disease]] |
| [[Category:Gastroenterology]] | | [[Category:Gastroenterology]] |
| [[Category:Infectious disease]]
| |
