Clostridium Difficile Infection CDI: Difference between revisions

No edit summary
No edit summary
 
(40 intermediate revisions by 9 users not shown)
Line 1: Line 1:
<div class="noeditbox">Welcome to [[Pathophysiology of Complex Patient Problems|PT 635 Pathophysiology of Complex Patient Problems]] This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!</div><div class="editorbox">
<div class="editorbox">
'''Original Editors '''- John Hardy[[Pathophysiology of Complex Patient Problems|&nbsp;from Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  
'''Original Editors '''- John Hardy[[Pathophysiology of Complex Patient Problems|&nbsp;from Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  


'''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}} &nbsp;  
'''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}} &nbsp;  
</div>  
</div>  
== Definition/Description  ==


&nbsp;&nbsp;&nbsp;&nbsp; Clostridium difficile is an anerobic, gram-positive bacillus. This rode shaped bacterium exists in vegetative or spore form and can survive harsh environments and common sterilization techniques. Clostridium difficile is resistant to ultra-violent light, high temperatures, and antibiotics. There are two distinct toxins which are the primary virulent factors for C. difficile: toxin A (Tcd A) and toxin B (Tcd B). Both toxins disrupt the acti cytoskeleton of tissue cells by preventing the activation of specific proteins (GTPases, Rho, Rac) that regulate actin polymerization. Originally, TcdA was believed to be the major virulence factor of C. Difficile, but recent evidence supports Tcd B as the primary factor not Tcd A. Approximately 70% of healthy newborns have detectable C. Difficile colonization by 18months of age. These infants rarely develop colitis and it is believed this asymptomatic colonization helps the body develop humoral immunity.<br>&nbsp;&nbsp;&nbsp;&nbsp; C. Diffile spores are ingested following contact with contaminated abiotic or biotic surfaces. C. Difficile has a propensity to colonize in the large bowel likely due to the anerobic environment and absence of native flora which is often depleted by antibiotic treatment. Bile salts are then utilized for spore germination. Following germination, the vegetative-cell type colonizes the host and begins to produce toxins. These toxins are then released causing cytotoxicity, tissue necrosis, inflammation, fluid secretion, and ultimately apoptosis of epithelial cells.<br>
== Introduction  ==
[[File:Clostridium difficile CDC.jpeg|thumb|Clostridium difficile]]
Clostridium Difficile Infections (CDI) are considered one of the most significant nosocomial infections which affect all hospitals worldwide. Clostridium difficile (C. Difficile) is an anaerobic, gram-positive, spore-forming bacillus [[Bacterial Infections|bacteria]] that can cause colitis, a serious [[Inflammation Acute and Chronic|inflammation]] of the colon. [[Infectious Disease|Infections]] from C. difficile often start after over-taking [[antibiotics]] and can sometimes be life-threatening<ref name=":0">Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nature reviews Disease primers. 2016 Apr 7;2(1):1-20.</ref>. This rode shaped bacterium exists in vegetative or spore form and can survive harsh environments and common sterilization techniques. Clostridium difficile is resistant to ultra-violent light, high temperatures, and antibiotics.<ref name="p2">Cecil J. Clostridium difficile: Changing Epidemiology, Treatment and Infection Prevention Measures. Current Infectious Disease Reports [serial online]. December 2012;14(6):612-619. Available from: MEDLINE, Ipswich, MA. Accessed March 17, 2014</ref>  


== Prevalence  ==
== Epidemiology ==
Clostridium difficile infection (CDI) has become a serious medical and epidemiological problem with approximately 5% of adults and 15 to 70% of children being colonized by C. difficile and the colonization prevalence further increases with hospitalized patients and patients in nursing homes<ref>Leffler DA, Lamont JT. Clostridium difficile infection. New England Journal of Medicine. 2015 Apr 16;372(16):1539-48.</ref>. Also, patients above the age of 65 are more at risk at developing CDI than younger patients<ref>Czepiel J, Kędzierska J, Biesiada G, Birczyńska M, Perucki W, Nowak P, Garlicki A. Epidemiology of Clostridium difficile infection: results of a hospital-based study in Krakow, Poland. Epidemiology & Infection. 2015 Nov;143(15):3235-43.</ref>. The incidence of CDIs also depends on the length of the hospitalization period where during the first few days of hospitalization the risk is between 2.1 to 20% and longer periods of hospitalization increase the risk to up to 45.4% of getting CDI<ref>Hung YP, Lin HJ, Wu TC, Liu HC, Lee JC, Lee CI, Wu YH, Wan L, Tsai PJ, Ko WC. Risk factors of fecal toxigenic or non-toxigenic Clostridium difficile colonization: impact of Toll-like receptor polymorphisms and prior antibiotic exposure. PloS one. 2013 Jul 25;8(7):e69577.</ref>. According to the Center for Disease Control and Prevention (CDC) C. difficile caused half a million infections and resulted in 15,000 deaths in a single year<ref name=":2">Medical news today What to know about Clostridium difficile Available:https://www.medicalnewstoday.com/articles/172329#what-is-c-difficile (accessed 12.5.2022)</ref>. Furthermore, according to a study the risk of CDI increases when the patient has co-morbidities where more than 63% of patients with CDIs were immunosuppressed<ref>Acheson ES, Galanis E, Bartlett K, Klinkenberg B. Climate Classification System–Based Determination of Temperate Climate Detection of Cryptococcus gattii sensu lato. Emerging Infectious Diseases. 2019 Sep;25(9):1723.</ref> and according to another study conducted by Oxford University the incidence of CDI is high ranging between 6 and 33% with immunosuppressed patients with cancer, HIV and solid organ transplant recipients<ref>Revolinski SL, Munoz-Price LS. Clostridium difficile in immunocompromised hosts: a review of epidemiology, risk factors, treatment, and prevention. Clinical Infectious Diseases. 2019 May 30;68(12):2144-53.</ref>. Prevention, proper diagnosis and effective treatment are necessary to reduce the risk for the patients, deplete the spreading of infection and diminish the probability of recurrent infection.


&nbsp; &nbsp; &nbsp;C. Difficile is commonly a nosocomial pathogen found in a hospital or similar healthcare facility. Colonization rate of healthy adults is estimated to be 2% while the prevalence of hospitalized adults can be high as 40%. Nearly a third of all C. Difficile infections are community acquired which suggests a recent increase in non-nosocmial infections. Risk factors for the disease are: prolonged antibiotic use (&gt;2 months), advanced age (&gt;65), hospitalization, and residency in a long-term care facility. Prolonged antibiotic exposure is considered the most significant risk factor at this time. Several recent studies have identified patients taking proton pump inhibitors (PPI) are much more susceptible to colonization than those who are not. Asseri et al found patients taking PPIs were 3.6 times more likely to acquire a C. Difficile infection than those who were not. Although, some researchers theorize that acid suppression is not responsible for increased infection rate, but is a marker of other co-morbidities that increase risk of C. Difficile infection (CDI). <br>&nbsp; &nbsp; &nbsp;As noted earlier prolonged antibiotic use and advanced age are two significant risk factors for CDI. Though prolonged antibiotic use seems to be most significant for initial infection, patients with advanced aged are most susceptible for disease reoccurrence. This increased infection and reoccurrence rate in the elderly is likely due to ineffective immune responses as well as insufficient recovery of commensal microbiota following treatment with anti-CDI antibiotics. Recurrent CDI typically occurs shortly after cessation of anit-CDI antibiotic pharmaceuticals with a reappearance of symptoms within 14-45 days. Reoccurance following anti-biotic therapy is primarily contributed to persistent alteration in gut flora of the patient. The causative strain of the CDI reoccurrence is molecularly identical to the original strain in many patients. First time reoccurrence rates have been documented as 33% and infection following previous reoccurrence as high as 45%.<br>&nbsp; &nbsp; &nbsp;A trend of increasing CDI rates was reported throughout the United States in the early 2000’s. Various studies aimed to identify the cause of this significant increase in infection rate and were able to identify particularly strains that were associated with higher rates of infection. Specifically, BI/NAP1/027 strain was identified as a strain primarily responsible for the increased infection rate. This particular strain exhibited an increased resistance to antibiotics used to treat CDI and produced more than twenties times more toxin than historical strains. This strain is also associated with infection of people not previously considered at risk including young, seemingly healthy individuals not exposed to a healthcare environment or prolonged antibiotic treatment. There is also an increased mortality rate in patients infected with BI/NAP1/027 when compared to traditional strains, especially in people 60-90 years old.<br><br>
== Pathological Process  ==
[[File:Hand hygeine.jpg|thumb|Hand Hygiene]]The infection with C. difficile occurs as a result of spore transmission. Spores are transmitted through the fecal-oral route, can survive up to several months and the pathogen is found all around us, being in the air, water, soil, and in the feces of humans and animals. In addition to that, the incubation period of this pathogen may be up to 3 days and is mostly individual-dependent<ref>McFarland LV, Mulligan ME, Kwok RY et al (1989) Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 320:204–210</ref>.


== Characteristics/Clinical Presentation ==
The main protective barrier against CDI is the normal intestinal flora so this bacterium does not usually cause problems for people who are healthy<ref>Allegretti JR, Kearney S, Li N, Bogart E, Bullock K, Gerber GK, Bry L, Clish CB, Alm E, Korzenik JR. Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles. Alimentary pharmacology & therapeutics. 2016 Jun;43(11):1142-53.</ref>. Patients who take antibiotic treatment have disruptions in their intestinal flora and are at higher risk of developing CDI<ref>Rineh A, Kelso MJ, Vatansever F, Tegos GP, Hamblin MR. Clostridium difficile infection: molecular pathogenesis and novel therapeutics. Expert review of anti-infective therapy. 2014 Jan 1;12(1):131-50.</ref>. After reaching the intestine, primary bile acids play an important role in the induction of C. difficile spore germination while the secondary ones inhibit it. This leads to changes in the fecal content of bile acids where normally there is a high concentration of secondary bile acids in healthy patients while with patients with CDI, there's a high concentration of primary bile acids<ref>Kochan TJ, Somers MJ, Kaiser AM, Shoshiev MS, Hagan AK, Hastie JL, Giordano NP, Smith AD, Schubert AM, Carlson Jr PE, Hanna PC. Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores. PLoS pathogens. 2017 Jul 13;13(7):e1006443.</ref>. When this balance is disrupted, C. difficile starts to colonize the large intestine and the infection begins. &nbsp;&nbsp;


&nbsp; &nbsp; &nbsp;Manifestations of CDI range from symptomless carriage, to mild-moderate diarrhea, to fatal pseudomembranous colitis. Fever, cramping, abdominal discomfort, and peripheral leukcytosis are common though found in less than half of patients with CDI. The passage of musucs, melena, or hematochezia are rare. Non-GI related symptoms such as arthritis and bacteremia have very rarely been reported in the literature. Patients who have undergone a complete colectomy have been reported to develop C. Difficile ileitis or puchitis in rare instances. Severe CDI can cause: dehydration, electrolyte disturbances, hypoalbuminemia, toxic megacolon, bowel perforation, hypotension, renal failure, sepsis, clonic ileus, toxic dilatation, systemic inflammatory response syndrome, and death. Patients presenting with unexplained leukocytosis should alarm the clinician and prompt them to request stool samples sent for diagnostic testing. <br>
== Clinical Presentation ==
The clinical state of CDI is heterogeneous and varies from mild to life-threatening. Some of the symptoms experienced include:  


== Associated Co-morbidities  ==
* Diarrhea
* Abdominal pain
* Vomiting
* Fever
* Stomach tenderness or pain
* Weakness
* Loss of appetite
* Nausea<ref>Johnson S, Clabots CR, Linn FV, Olson MM, Peterson LR, Gerding DN. Nosocomial Clostridium difficile colonisation and disease. The Lancet. 1990 Jul 14;336(8707):97-100.</ref>
In the most severe clinical presentation of CDI, symptoms are more life-threatening and include:


&nbsp; &nbsp; &nbsp;Co-morbidities such as cancer, old age, and renal disease were significantly correlated with a higher rate of mortality from CDI in an English Cohort study of over 2,000 people . Other significant risk factors mentioned in previous sections including: inflammatory bowel disease, immunocompromise, chemotherapy, abdominal surgery, gastrointestinal procedure, previous C. Difficile infection.<br>
* Severe diarrhea
* Severe cramping
* Fever
* Nausea
* Loss of appetite/ weight loss
* [[Dehydration]]
* [[Tachycardia|Rapid heart rate]]
* Abdominal distension
* Hypoalbuminemia with peripheral edema
* Circulatory shock
In addition to other severe symptoms like peritonitis, [[Sepsis|septicemia]], perforation of the colon, kidney failure, systemic inflammatory response syndrome, intestinal paralysis and megacolon<ref name=":1">McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clinical infectious diseases. 2018 Apr 1;66(7):e1-48.</ref>. 


== Medications<ref name="12" />  ==
== Diagnostic Procedures  ==


- Vancomycin (Glycopeptide Antibiotics)<br>-Metroidazole (Nirtoimidazole Antibiotic)<br>- Rifamimin (Antimicrobial)<br>-Probiotics<br>-Immunosuppressants<br>&nbsp;<br>
For definitive diagnosis, a stool sample must be collected. Tests include:


== Diagnostic Tests/Lab Tests/Lab Values  ==
* [[Enzymes|Enzyme]] Immunoassay (EIA) which detects C. difficile toxins
* Nucleic Acid Amplification Test (NAAT)
* Glutamate Dehydrogenase (GDH) which detects C. difficile antigens
* Cell Cytotoxicity Assay Test (CYTA) <ref>Simor AE. Diagnosis, management, and prevention of Clostridium difficile infection in long‐term care facilities: A review. Journal of the American Geriatrics Society. 2010 Aug;58(8):1556-64.</ref>
In some cases, endoscopic evaluation is useful and is normally not performed with patients with uncomplicated CDI usually confirmed with immunological tests<ref>Hookman P, Barkin JS. Clostridium difficile associated infection, diarrhea and colitis. World journal of gastroenterology: WJG. 2009 Apr 4;15(13):1554.</ref>. An abdominal X-ray may also be ordered in order to check for distended bowel loops, often with wall thickening<ref>Vaishnavi C. Clinical spectrum & pathogenesis of Clostridium difficile associated diseases. Indian Journal of Medical Research. 2010 Apr 1;131(4):487-99.</ref>. In addition to that, a computed tomography (CT) of the pelvis and abdomen may be ordered to check for the presence of megacolon, bowel perforation and other findings to check if a surgical intervention is needed<ref>Paláu-Dávila L, Lara-Medrano R, Negreros-Osuna AA, Salinas-Chapa M, Garza-González E, Gutierrez-Delgado EM, Camacho-Ortiz A. Efficacy of computed tomography for the prediction of colectomy and mortality in patients with Clostridium difficile infection. Annals of Medicine and Surgery. 2016 Dec 1;12:101-5.</ref>.


&nbsp; &nbsp; &nbsp;For definitive diagnosis a stool sample must be collected and tested for the antigen glutamate dehydrogenase (GDH). Testing for this antigen can be completed several different ways and is commonly done so via enzyme-linked immunisirbent assay (ELISA) or immunochromatographic assay. GD functions as cell-wall protein produced by the C. Difficile bacteria in considerably higher amounts than toxins. If GDH, TcdA, and TcdB are all present the physician can definitively diagnose the patient with CDI. There are a number of different tests used for identification of these markers, all of which have varying levels of psychometric properties. If all three markers are not present subsequent tests will be performed that are more specific to the missing markers before CDI is ruled out by the physician. Other tests occasionally used are sigmoidoscopy and colonoscopy. These tests are not frequently used because only ~50% of CDIs have visible pseudomembrane formation. Thickening of the colon wall and pericolonic stranding are sometimes evident on radiographs and referred to as “accordion sign” and or “double-halo sign.”<ref name="7">Heinlen L, Ballard J. 2010. Clostridium difficile infection. Am. J. Med. Sci.340:247–252. Accessed March 12, 2014</ref><ref name="8" /><br>
== Management ==


&nbsp;  
=== Medical Management ===
The treatment of CDIs should start only when the patient experiences symptoms. Some of the treatment options include:
* Metronidazole is the first-line drug in non-severe CDI while vancomycin is the drug of choice for severe CDI<ref>Debast SB, Bauer MP, Kuijper EJ, Committee. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clinical microbiology and infection. 2014 Mar;20:1-26.</ref>
* Probiotics: used to help restore a healthful balance in the intestine. Saccharomyces boulardii (S. boulardii), a natural yeast, can reduce recurring C. difficile infections when a person takes it together with antibiotics but there aren't enough studies proving their efficiency in preventing or treating CDI <ref name=":1" />
* Surgery: If symptoms are severe, or if there is organ failure or perforation of the lining of the abdominal wall, it may be necessary to surgically remove the affected part of the colon.
* Fecal microbiota transplantation (FMT): Medical professionals are now using fecal transplants in recurrent cases of C. difficile infection. A healthcare provider will transfer bacteria from a healthy person’s colon into the colon of a person with C. difficile<ref>Shin YJ, Lee BJ. Fecal Microbiota Transplantation as a Treatment of Recurrent Clostridium difficile Infection: Where Are We Now and Where Are We Heading?. The Korean Journal of Gastroenterology. 2017 Apr 1;69(4):203-5.</ref>.


'''Double Halo Sign<sup>1</sup>'''
=== Physical Therapy Management ===


[[Image:Double Halo Sign.jpg|150x112px]]
C. difficile infections are primarily managed through pharmaceutical therapy and associated medical treatments. The therapist should take an active role in [[Infection Prevention and Control|infection control]] and prevention measures whenever working with these patients. Infection control measures include: donning gloves and gowns prior to entering patients room, washing hands with soap and water upon departure, treating patients in a private room and educating visitors on proper hygiene measures. Routine environmental screening and use of chlorine-containing cleaning agents is also recommended. [[File:C. difficile spreads.png|center|frameless|691x691px]]
 
== Etiology/Causes  ==
 
&nbsp;&nbsp;&nbsp;&nbsp; C. Difficile bacteria colonize the large colon after exposure. Colonization in areas other than the large colon is quite rare in the human body. The natural anaerobic environment and absence of competing gut flora (due to antibiotic treatment) make the large colon an ideal environment for the bacteria to flourish.For the bacteria to flourish in the gut and damage the host several events must occur so that toxin production is possible. To start, the C. difficile spores must reach an area in the gut where an ample amount of bile salts are present so that they can catalyze the germination of these spores.<ref name="8">Knetsch C, Lawley T, Hensgens M, Corver J, Wilcox M, Kuijper E. Current application and future perspectives of molecular typing methods to study Clostridium difficile infections. Euro Surveillance: Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin [serial online]. January 24, 2013;18(4):20381. Available from: MEDLINE, Ipswich, MA. Accessed March 12, 2014</ref><ref name="4" /><ref name="2" />&nbsp;<br>&nbsp;&nbsp;&nbsp;&nbsp; After germination is complete, the bacteria begins produce toxins, initially focusing on a binary toxin that produces microtubule-cell extensions allowing adherence of the bacteria to the intestinal walls. During colonization and immediately following, C. difficile now in a vegetative form releases TcdA and TcdB. The mechanism of A and B toxin secretion is not fully understood, but the it is known that amion acid availability is critical to toxin expression. Primarily acting on the epithelial cells of the intestines, TcdA causes inflammation, fluid secretion, and necrosis of colon tissue. TcdB is a potent cytoxin that may be responsible for systemic damaged present in patients with fulminant CDI due to its cardiotoxic behavior.<ref name="8" /><ref name="4" /><ref name="2" /> <br>
 
== Systemic Involvement<ref name="12" />  ==
 
-Dehydration<br>-Ectrolyte disturbances<br>-Hypoalbuminemia<br>-Toxic megacolon<br>-Bowel perforation<br>-Rrenal failure<br>-Sepsis<br>-Clonic ileus<br>-Toxic dilatation<br>-Systemic inflammatory response syndrome<br>-Death
 
== Medical Management (current best evidence)  ==
 
&nbsp;&nbsp;&nbsp;&nbsp; Medical management of CDI depends on the acuity and severity of the infection as well as whether it is an initial or recurrent infection. It is widely recognized that the most important first step in treatment is to discontinue the inciting antibiotic. Discontinuation of antibiotic treatment historically resulted in resolution of the infection, but due to new hypervirulent strains further intervention is recommended. Fluid and electrolyte replacement is suggested for quicker recovery. The available drugs for treatment of a CDI are Vancomycin and Metronidazole. If Vancomycin is the drug selected for treatment it should be administered either rectally or orally. These are the recommended routes of administration because intravenous Vancomycin has shown to be an ineffective treatment of CDI.<ref name="5" /><br>&nbsp;&nbsp;&nbsp;&nbsp; On the other hand, Metronidazole has been shown to deliver similar colonic and intraluminal levels regardless of administration. Some researchers advocate oral administration when possible to avoid potential complications with an intravenous route. Though Metronidazole has been shown to be equally as effective as Vancomycin it has a higher rate of unresponsiveness. If patients do not respond to Metronidazole, Vancomycin is then considered. Vancomycin is more commonly the first treatment especially in severe cases of CDI due its lower rate of unresponsiveness and superior efficacy.<ref name="2">Cecil J. Clostridium difficile: Changing Epidemiology, Treatment and Infection Prevention Measures. Current Infectious Disease Reports [serial online]. December 2012;14(6):612-619. Available from: MEDLINE, Ipswich, MA. Accessed March 17, 2014</ref><ref name="5">Drekonja D, Butler M, Wilt T, et al. Comparative Effectiveness of Clostridium difficile Treatments: A Systematic Review. Annals Of Internal Medicine [serial online]. December 20, 2011;155(12):839-847. Available from: CINAHL, Ipswich, MA. Accessed March 14, 2014</ref><br>&nbsp;&nbsp;&nbsp;&nbsp; Mild to moderate cases of CDI are treated with 25o mg of metronidazole every six hours or 125 mg of vacomycin every 6 hours. Treatment course is typically 10-14 days with resolution of symptoms in more than 90% of cases in less than 10 days. Combined use of these drugs is often used in patients with moderate to severe infection especially if accompanied by ileus and or toxic megacolon. Patients with unresolving ileus can be given increased doses as well as frequency of administration (i.e. 500 mg every 6 hours). In severe cases surgical evaluation for colectomy may be indicated to avoid life-threatening complications. In patients with reoccurrent infection pulse or tapering therapy is combined with vancomycin treatment. A course of Rifamimin is also recommended after previous treatments have failed.<ref name="5" /><ref name="11" />
 
== Physical Therapy Management (current best evidence)  ==
 
&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;C. difficile infections are primarily managed through pharmaceutical therapy and associated medical treatments. Exercise recommendations for patients with CDI have not been clearly established and are currently based on clinical decision making of the therapeutic team and treating physician. The therapist should take an active role in infection control and prevention measures whenever working with these patients. Infection control measures include: donning gloves and gowns prior to entering patients room, washing hands with soap and water upon departure, treating patients in a private room, educating visitors on proper hygiene measures. Routine environmental screening and use of chlorine-containing cleaning agents is also recommended. Below is a table summarizing the evidence supporting various infection control measures.<ref name="4">Cohen S, Gerding D, Wilcox M, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infection Control &amp; Hospital Epidemiology [serial online]. May 2010;31(5):431-455. Available from: CINAHL, Ipswich, MA. Accessed March 12, 2014.</ref>
 
== Alternative/Holistic Management (current best evidence)  ==
 
&nbsp;&nbsp;&nbsp;&nbsp; Though patients with CDI have a disturbance in native-gut flora, antimicrobial pharmaceuticals are being investigated as a potential treatment option. There are several antimicrobials under investigation including: tinidazole, rifaximin, rifalazil, nitazoxanide, glycopeptides derivatives, fidoxamicin, and topical bacitracin.<ref name="5" /><br>&nbsp;&nbsp;&nbsp;&nbsp; Probiotics have also been proposed as a potential treatment option though evidence is not strong enough for it be considered as a primary option. Theoretically probiotics may replenish the native-flora of the colon which was depleted by prolonged anti-biotic treatment. This native flora would then compete with the C. difficile strains for nutrients and habitable space in the colon. Probiotics are reportedly non-pathogenic microorganisms though are not used in immunocompromised patients because of cases of blood-borne infections. The most widely studied probiotics are Saccharomyces and Lactobacillus. Moderate improvements have been demonstrated when probiotics are used in conjunction with vancomycin or metronidazol when compared to the ladder drugs alone. A single case report, demonstrated the effectiveness of reducing the incidence of CDI through concurrent treatment administration of probiotics and antimicrobials.<ref name="10">McFarland L. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. The American Journal Of Gastroenterology [serial online]. April 2006;101(4):812-822. Available from: MEDLINE, Ipswich, MA. Accessed March 12, 2014</ref>
 
&nbsp;&nbsp;&nbsp;&nbsp; Another developing treatment strategy is immunotherapy. Inconsistent results have been reported as to whether intravenous administration of human immunoglobulin can neutralize C. difficile toxins A and B in recurrent and sever CDIs. Recent research has reported when given in conjunction with vancomycin, human monoclonal antibodies can significantly reduce the reoccurance rate of CDI.<br>Lastly, research goal of practically every infectious disease is to develop a safe and effective vaccine. Research on a C. difficile vaccine is currently taking place and shown promising results in both animal and human volunteers. Since thorough analysis has not been performed on a large sample of patients its safety and efficacy to date is not established.<ref name="5">Drekonja D, Butler M, Wilt T, et al. Comparative Effectiveness of Clostridium difficile Treatments: A Systematic Review. Annals Of Internal Medicine [serial online]. December 20, 2011;155(12):839-847. Available from: CINAHL, Ipswich, MA. Accessed March 14, 2014</ref>
 
== Differential Diagnosis<br> ==
<div>&nbsp; &nbsp; &nbsp;Diarrhea is defined as an abnormal increase in stool frequency and liquidity. This can be accompanied by incontinence, urgency, and perineal discomfort. There are numerous causes of diarrhea including: food, alcohol, use of laxativies, pharmaceutical side effects, and travel. When an acute episode of diarrhea is associated with fever, cramps, and blood or pus in the stool can be indicative of an invasive enteric infection. Chronic diarrhea associated with weight loss and nigh pain may be indicative of a neoplasm or inflammatory bowel disease. Extraintestinal symptoms such as arthritis as well as lesions to the skin and eye are also commonly present in inflammatory bowel disease.<ref name="11">Surawicz C, Brandt L, Zuckerbraun B, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. The American Journal Of Gastroenterology [serial online]. April 2013;108(4):478-498. Available from: MEDLINE, Ipswich, MA. Accessed March 12, 2014</ref><br>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;A more comprehensive list of potential causes of diarrhea and potential differential diagnoses include: pancreatitis, pancreatic carcinoma, Crohn’s disease, Irritable bowel syndrome, diabetic enteropathy, hyperthyroidism, caffeine, incomplete obstruction, fecal impaction, muscular incompetency, ileal bypass, viral infection, bacterial infection, parasitic infection, protozoal infection (Giardia), ulcerative colitis, diverticulitis, food allergy, creatine use, chemotherapy, lactose intolerance, psychogenic (nervous tension). A thorough assessment of patients history, signs, symptoms, risk factors, and lab tests are necessary for an accurate diagnosis.<ref name="12">Welfare M, Lalayiannis L, Martin K, Corbett S, Marshall B, Sarma J. Co-morbidities as predictors of mortality in Clostridium difficile infection and derivation of the ARC predictive score. Journal Of Hospital Infection [serial online]. December 2011;79(4):359-363. Available from: CINAHL, Ipswich, MA. Accessed March 14, 2014</ref></div><div><br>&nbsp;<br><br></div>
 
== Case Reports/ Case Studies  ==
 
A. Loshkajian. Pseudomembranous Colitis. Available at: http://www.eurorad.org/eurorad/case.php?id=1368. Accessed March, 17, 2014
 
'''Other Cases''':<br>Pron B, Merckx J, Gaillard J, et al. Chronic septic arthritis and osteomyelitis in a prosthetic knee joint due to Clostridium difficile. European Journal Of Clinical Microbiology &amp; Infectious Diseases: Official Publication Of The European Society Of Clinical Microbiology [serial online]. July 1995;14(7):599-601. Available from: MEDLINE, Ipswich, MA. Accessed March 12, 2014.<br>
 
Bermejo C, Maseda E, Salgado P, Gabilondo G, Gilsanz F. [Septic shock due to a community acquired Clostridium difficile infection. A case study and a review of the literature.]. Revista Espanola De Anestesiologia Y Reanimacion[serial online]. June 1, 2013;Available from: MEDLINE, Ipswich, MA. Accessed March 12, 2014.<br>
 
 
 
Leonard A, Ho K, Flexman J. Proton pump inhibitors and diarrhoea related to Clostridium difficile infection in hospitalised patients: a case-control study. Internal Medicine Journal [serial online]. May 2012;42(5):591-594. Available from: Academic Search Premier, Ipswich, MA. Accessed March 12, 2014.<br>
 
De Almeida M, Heffernan H, Roberts S, et al. Severe Clostridium difficile infection in New Zealand associated with an emerging strain, PCR-ribotype 244. The New Zealand Medical Journal [serial online]. August 16, 2013;126(1380):9-14. Available from: MEDLINE, Ipswich, MA. Accessed March 12, 2014.<br><br>
 
== Resources <br>  ==
 
http://www.cdc.gov/HAI/organisms/cdiff/Cdiff_infect.html
 
http://www.apic.org/Professional-Practice/CDIresources
 
http://www.in.gov/isdh/files/CDI_ResourceManual.pdf<br><br>
 
== Recent Related Research (from [http://www.ncbi.nlm.nih.gov/pubmed/ Pubmed])<br> ==
<div class="researchbox">
<rss>http://www.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1P_FVbJaBNrCLU7cEFzJxrAyjGKTqNTnEe9vV2EzjLL0lYgYRP|charset=UTF-8|short|max=10</rss>
</div>


== References  ==
== References  ==
see [[Adding References|adding references tutorial]].
<br>Bellarmine_Student_Project
<br>


<references />
<references />
[[Category:Communicable Diseases]]
[[Category:Infection prevention and control]]

Latest revision as of 22:40, 24 February 2023

Original Editors - John Hardy from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - John Hardy, Lucinda hampton, Reem Ramadan, Elaine Lonnemann, 127.0.0.1, WikiSysop, Oyemi Sillo, Kim Jackson, Vidya Acharya and Nupur Smit Shah  

Introduction[edit | edit source]

Clostridium difficile

Clostridium Difficile Infections (CDI) are considered one of the most significant nosocomial infections which affect all hospitals worldwide. Clostridium difficile (C. Difficile) is an anaerobic, gram-positive, spore-forming bacillus bacteria that can cause colitis, a serious inflammation of the colon. Infections from C. difficile often start after over-taking antibiotics and can sometimes be life-threatening[1]. This rode shaped bacterium exists in vegetative or spore form and can survive harsh environments and common sterilization techniques. Clostridium difficile is resistant to ultra-violent light, high temperatures, and antibiotics.[2]

Epidemiology[edit | edit source]

Clostridium difficile infection (CDI) has become a serious medical and epidemiological problem with approximately 5% of adults and 15 to 70% of children being colonized by C. difficile and the colonization prevalence further increases with hospitalized patients and patients in nursing homes[3]. Also, patients above the age of 65 are more at risk at developing CDI than younger patients[4]. The incidence of CDIs also depends on the length of the hospitalization period where during the first few days of hospitalization the risk is between 2.1 to 20% and longer periods of hospitalization increase the risk to up to 45.4% of getting CDI[5]. According to the Center for Disease Control and Prevention (CDC) C. difficile caused half a million infections and resulted in 15,000 deaths in a single year[6]. Furthermore, according to a study the risk of CDI increases when the patient has co-morbidities where more than 63% of patients with CDIs were immunosuppressed[7] and according to another study conducted by Oxford University the incidence of CDI is high ranging between 6 and 33% with immunosuppressed patients with cancer, HIV and solid organ transplant recipients[8]. Prevention, proper diagnosis and effective treatment are necessary to reduce the risk for the patients, deplete the spreading of infection and diminish the probability of recurrent infection.

Pathological Process[edit | edit source]

Hand Hygiene

The infection with C. difficile occurs as a result of spore transmission. Spores are transmitted through the fecal-oral route, can survive up to several months and the pathogen is found all around us, being in the air, water, soil, and in the feces of humans and animals. In addition to that, the incubation period of this pathogen may be up to 3 days and is mostly individual-dependent[9].

The main protective barrier against CDI is the normal intestinal flora so this bacterium does not usually cause problems for people who are healthy[10]. Patients who take antibiotic treatment have disruptions in their intestinal flora and are at higher risk of developing CDI[11]. After reaching the intestine, primary bile acids play an important role in the induction of C. difficile spore germination while the secondary ones inhibit it. This leads to changes in the fecal content of bile acids where normally there is a high concentration of secondary bile acids in healthy patients while with patients with CDI, there's a high concentration of primary bile acids[12]. When this balance is disrupted, C. difficile starts to colonize the large intestine and the infection begins.   

Clinical Presentation[edit | edit source]

The clinical state of CDI is heterogeneous and varies from mild to life-threatening. Some of the symptoms experienced include:

  • Diarrhea
  • Abdominal pain
  • Vomiting
  • Fever
  • Stomach tenderness or pain
  • Weakness
  • Loss of appetite
  • Nausea[13]

In the most severe clinical presentation of CDI, symptoms are more life-threatening and include:

  • Severe diarrhea
  • Severe cramping
  • Fever
  • Nausea
  • Loss of appetite/ weight loss
  • Dehydration
  • Rapid heart rate
  • Abdominal distension
  • Hypoalbuminemia with peripheral edema
  • Circulatory shock

In addition to other severe symptoms like peritonitis, septicemia, perforation of the colon, kidney failure, systemic inflammatory response syndrome, intestinal paralysis and megacolon[14].

Diagnostic Procedures[edit | edit source]

For definitive diagnosis, a stool sample must be collected. Tests include:

  • Enzyme Immunoassay (EIA) which detects C. difficile toxins
  • Nucleic Acid Amplification Test (NAAT)
  • Glutamate Dehydrogenase (GDH) which detects C. difficile antigens
  • Cell Cytotoxicity Assay Test (CYTA) [15]

In some cases, endoscopic evaluation is useful and is normally not performed with patients with uncomplicated CDI usually confirmed with immunological tests[16]. An abdominal X-ray may also be ordered in order to check for distended bowel loops, often with wall thickening[17]. In addition to that, a computed tomography (CT) of the pelvis and abdomen may be ordered to check for the presence of megacolon, bowel perforation and other findings to check if a surgical intervention is needed[18].

Management[edit | edit source]

Medical Management[edit | edit source]

The treatment of CDIs should start only when the patient experiences symptoms. Some of the treatment options include:

  • Metronidazole is the first-line drug in non-severe CDI while vancomycin is the drug of choice for severe CDI[19]
  • Probiotics: used to help restore a healthful balance in the intestine. Saccharomyces boulardii (S. boulardii), a natural yeast, can reduce recurring C. difficile infections when a person takes it together with antibiotics but there aren't enough studies proving their efficiency in preventing or treating CDI [14]
  • Surgery: If symptoms are severe, or if there is organ failure or perforation of the lining of the abdominal wall, it may be necessary to surgically remove the affected part of the colon.
  • Fecal microbiota transplantation (FMT): Medical professionals are now using fecal transplants in recurrent cases of C. difficile infection. A healthcare provider will transfer bacteria from a healthy person’s colon into the colon of a person with C. difficile[20].

Physical Therapy Management[edit | edit source]

C. difficile infections are primarily managed through pharmaceutical therapy and associated medical treatments. The therapist should take an active role in infection control and prevention measures whenever working with these patients. Infection control measures include: donning gloves and gowns prior to entering patients room, washing hands with soap and water upon departure, treating patients in a private room and educating visitors on proper hygiene measures. Routine environmental screening and use of chlorine-containing cleaning agents is also recommended.

C. difficile spreads.png

References[edit | edit source]

  1. ↑ Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nature reviews Disease primers. 2016 Apr 7;2(1):1-20.
  2. ↑ Cecil J. Clostridium difficile: Changing Epidemiology, Treatment and Infection Prevention Measures. Current Infectious Disease Reports [serial online]. December 2012;14(6):612-619. Available from: MEDLINE, Ipswich, MA. Accessed March 17, 2014
  3. ↑ Leffler DA, Lamont JT. Clostridium difficile infection. New England Journal of Medicine. 2015 Apr 16;372(16):1539-48.
  4. ↑ Czepiel J, Kędzierska J, Biesiada G, Birczyńska M, Perucki W, Nowak P, Garlicki A. Epidemiology of Clostridium difficile infection: results of a hospital-based study in Krakow, Poland. Epidemiology & Infection. 2015 Nov;143(15):3235-43.
  5. ↑ Hung YP, Lin HJ, Wu TC, Liu HC, Lee JC, Lee CI, Wu YH, Wan L, Tsai PJ, Ko WC. Risk factors of fecal toxigenic or non-toxigenic Clostridium difficile colonization: impact of Toll-like receptor polymorphisms and prior antibiotic exposure. PloS one. 2013 Jul 25;8(7):e69577.
  6. ↑ Medical news today What to know about Clostridium difficile Available:https://www.medicalnewstoday.com/articles/172329#what-is-c-difficile (accessed 12.5.2022)
  7. ↑ Acheson ES, Galanis E, Bartlett K, Klinkenberg B. Climate Classification System–Based Determination of Temperate Climate Detection of Cryptococcus gattii sensu lato. Emerging Infectious Diseases. 2019 Sep;25(9):1723.
  8. ↑ Revolinski SL, Munoz-Price LS. Clostridium difficile in immunocompromised hosts: a review of epidemiology, risk factors, treatment, and prevention. Clinical Infectious Diseases. 2019 May 30;68(12):2144-53.
  9. ↑ McFarland LV, Mulligan ME, Kwok RY et al (1989) Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 320:204–210
  10. ↑ Allegretti JR, Kearney S, Li N, Bogart E, Bullock K, Gerber GK, Bry L, Clish CB, Alm E, Korzenik JR. Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles. Alimentary pharmacology & therapeutics. 2016 Jun;43(11):1142-53.
  11. ↑ Rineh A, Kelso MJ, Vatansever F, Tegos GP, Hamblin MR. Clostridium difficile infection: molecular pathogenesis and novel therapeutics. Expert review of anti-infective therapy. 2014 Jan 1;12(1):131-50.
  12. ↑ Kochan TJ, Somers MJ, Kaiser AM, Shoshiev MS, Hagan AK, Hastie JL, Giordano NP, Smith AD, Schubert AM, Carlson Jr PE, Hanna PC. Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores. PLoS pathogens. 2017 Jul 13;13(7):e1006443.
  13. ↑ Johnson S, Clabots CR, Linn FV, Olson MM, Peterson LR, Gerding DN. Nosocomial Clostridium difficile colonisation and disease. The Lancet. 1990 Jul 14;336(8707):97-100.
  14. ↑ 14.0 14.1 McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clinical infectious diseases. 2018 Apr 1;66(7):e1-48.
  15. ↑ Simor AE. Diagnosis, management, and prevention of Clostridium difficile infection in long‐term care facilities: A review. Journal of the American Geriatrics Society. 2010 Aug;58(8):1556-64.
  16. ↑ Hookman P, Barkin JS. Clostridium difficile associated infection, diarrhea and colitis. World journal of gastroenterology: WJG. 2009 Apr 4;15(13):1554.
  17. ↑ Vaishnavi C. Clinical spectrum & pathogenesis of Clostridium difficile associated diseases. Indian Journal of Medical Research. 2010 Apr 1;131(4):487-99.
  18. ↑ Paláu-Dávila L, Lara-Medrano R, Negreros-Osuna AA, Salinas-Chapa M, Garza-González E, Gutierrez-Delgado EM, Camacho-Ortiz A. Efficacy of computed tomography for the prediction of colectomy and mortality in patients with Clostridium difficile infection. Annals of Medicine and Surgery. 2016 Dec 1;12:101-5.
  19. ↑ Debast SB, Bauer MP, Kuijper EJ, Committee. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clinical microbiology and infection. 2014 Mar;20:1-26.
  20. ↑ Shin YJ, Lee BJ. Fecal Microbiota Transplantation as a Treatment of Recurrent Clostridium difficile Infection: Where Are We Now and Where Are We Heading?. The Korean Journal of Gastroenterology. 2017 Apr 1;69(4):203-5.
Retrieved from "https://www.physio-pedia.com/index.php?title=Clostridium_Difficile_Infection_CDI&oldid=327647"