Materiały źródłowe

• #1 C. diff Infection: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/15548-c-diff-infection

  C. diff infection (CDI) is a global health concern, although the exact rates of infection worldwide are unknown. In the U.S., 500,000 infections cause 15,000 deaths each year. […] If your healthcare provider suspects C. diff infection based on your symptoms, they’ll take a sample of your poop and send it to a lab. The lab will test it for C. diff toxins. […] If you test positive, your healthcare provider may conduct further tests to find out how severe the infection is. These may include blood tests and imaging tests that look inside your colon. […] Treatment for C. diff infection is based on how severe it is. If you developed a C. diff infection while taking antibiotics, your provider might begin by simply stopping those medications. […] For some people, this is enough. Their natural gut immunity returns and overcomes the infection. If this doesn’t happen, your provider will prescribe antibiotics that can stop C. diff.

• #2 C. difficile infection – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/c-difficile/diagnosis-treatment/drc-20351697

  A diagnosis of C. difficile infection is based on having: […] C. difficile in a stool sample. […] If C. difficile infection is suspected, one or more tests of a stool sample can show either the toxins or strains of the bacteria that produce toxins. […] Rarely, to help confirm a diagnosis of C. difficile infection, a health care provider might check the inside of the colon. […] An X-ray of the stomach area or a CT scan can look for possible complications of C. difficile infection.

• #3 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA

  https://www.idsociety.org/practice-guideline/clostridium-difficile/

  A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. […] CDI is defined by the presence of symptoms (usually diarrhea) and either a stool test positive for C. difficile toxins or detection of toxigenic C. difficile, or colonoscopic or histopathologic findings revealing pseudomembranous colitis. […] Patients with unexplained and new-onset 3 unformed stools in 24 hours are the preferred target population for testing for CDI. […] Use a stool toxin test as part of a multistep algorithm (ie, glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no preagreed institutional criteria for patient stool submission.

• #4 About C. diff | C. diff | CDC

  https://www.cdc.gov/c-diff/about/index.html

  If a healthcare professional suspects C. diff infection, they will review your symptoms and order a lab test of a stool (poop) sample. […] Developing diarrhea is common while on or after taking antibiotics. Only in a few cases is that diarrhea caused by C. diff infection. If your diarrhea is severe, do not delay getting medical care. […] If you have been taking antibiotics recently and have symptoms of C. diff infection, contact a healthcare professional.

• #5 Clostridioides difficile Infection: Update on Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/0201/p168.html

  Guidelines for the diagnosis and treatment of Clostridioides difficile infection have recently been updated. […] Testing in these patients should start with enzyme immunoassays for glutamate dehydrogenase and toxins A and B or nucleic acid amplification testing. […] A two-step algorithm should be used to guide diagnostic testing for Clostridioides difficile infection: enzyme immunoassay for glutamate dehydrogenase and toxins A and B, followed by nucleic acid amplification testing if initial results are indeterminate. […] The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America recommend limiting testing for Clostridium difficile infection to patients with unexplained onset of three or more unformed stools in 24 hours while not taking laxatives.

• #6

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/

  Therefore, accurate clinical and laboratory diagnosis is essential for prompt patient management and effective infection control measures. Recent practice guidelines emphasize that the targeted populations for C. difficile testing are patients with unexplained and new-onset unformed stools in 24 hours. However, the optimum laboratory based approach is still a matter of debate and controversy. A variety of methods exist for testing patients at risk for C. difficile. These can be broadly categorized into two groups: (1) those tests that detect the organism itself (or a component of the organism), such as anaerobic bacterial culture, glutamate dehydrogenase (GDH), the common antigen present in both toxigenic and nontoxigenic strains, and nucleic acid tests that detect the genes that encode toxins A and B; and (2) tests that detect free toxin, such as cell culture cytotoxicity neutralization assays (CCCNA) and enzyme immunoassays (EIAs). Bacterial culture with toxin testing of recovered isolates (toxigenic culture [TC]) and CCCNA are considered reference methods and the standards against which other methods are compared.

• #7 Clostridioides difficile – Antigen, PCR, Susceptibility, and Typing | Public Health Ontario

  https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Clostridium-difficile

  As per the Infectious Diseases Society of America and Society for Health Epidemiology America (IDSA/SHEA) guidelines, C. difficile testing is indicated for individuals with unexplained diarrhea (e.g. three unformed feces per day without underlying diarrheal condition such as laxative use) and with risk factors of C. difficile disease (e.g. systemic antibiotic therapy, hospitalization, advanced age, impaired immunity, gastrointestinal surgery). […] C. difficile testing is not indicated for asymptomatic individuals due to the possibility of clinically insignificant toxigenic C. difficile excretion in healthy individuals. Similarly, testing is not routinely indicated in patients under 12 months of age with diarrheal symptoms due to the high rate of concomitant C. difficile colonization in healthy newborns and infants. Repeat testing to monitor treatment response (or test of cure) is also not indicated, as test results may remain positive for weeks to months despite resolution of infection.

• #8 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA

  https://www.idsociety.org/practice-guideline/clostridium-difficile/

  Use a NAAT alone or a multistep algorithm for testing (ie, GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than a toxin test alone when there are preagreed institutional criteria for patient stool submission. […] Do not perform repeat testing (within 7 days) during the same episode of diarrhea and do not test stool from asymptomatic patients, except for epidemiological studies. […] There are insufficient data to recommend use of biologic markers as an adjunct to diagnosis. […] Because of the high prevalence of asymptomatic carriage of toxigenic C. difficile in infants, testing for CDI should never be routinely recommended for neonates or infants 12 months of age with diarrhea. […] C. difficile testing should not be routinely performed in children with diarrhea who are 12 years of age unless other infectious or noninfectious causes have been excluded. […] In children 2 years of age, C. difficile testing is recommended for patients with prolonged or worsening diarrhea and risk factors (eg, underlying inflammatory bowel disease or immunocompromising conditions) or relevant exposures (eg, contact with the healthcare system or recent antibiotics).

• #9 Clostridioides difficile – Antigen, PCR, Susceptibility, and Typing | Public Health Ontario

  https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Clostridium-difficile

  As per the Infectious Diseases Society of America and Society for Health Epidemiology America (IDSA/SHEA) guidelines, C. difficile testing is indicated for individuals with unexplained diarrhea (e.g. three unformed feces per day without underlying diarrheal condition such as laxative use) and with risk factors of C. difficile disease (e.g. systemic antibiotic therapy, hospitalization, advanced age, impaired immunity, gastrointestinal surgery). […] C. difficile testing is not indicated for asymptomatic individuals due to the possibility of clinically insignificant toxigenic C. difficile excretion in healthy individuals. Similarly, testing is not routinely indicated in patients under 12 months of age with diarrheal symptoms due to the high rate of concomitant C. difficile colonization in healthy newborns and infants. Repeat testing to monitor treatment response (or test of cure) is also not indicated, as test results may remain positive for weeks to months despite resolution of infection.

• #10 Clinical Testing and Diagnosis for CDI | C. diff | CDC

  https://www.cdc.gov/c-diff/hcp/diagnosis-testing/index.html

  There are four laboratory tests used to diagnose Clostridioides difficile infection or CDI. […] FDA-approved PCR assays are same-day tests that are highly sensitive and specific for the presence of a toxin-producing C. diff organism. […] Molecular assays can be positive for C. diff in asymptomatic individuals and those who do not have an infection. […] When using multi-pathogen (multiplex) molecular methods, read the results with caution as the pre-test probability of C. diff infection might be less. […] These rapid tests (1 hour) detect the presence of C. diff antigen glutamate dehydrogenase (GDH). […] Because results of antigen testing alone are nonspecific, antigen assays have been employed in combination with tests for toxin detection, PCR, or toxigenic culture in two-step testing algorithms.

• #11

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/

  Currently, there is no FDA-approved single rapid test that can be reliably used to diagnose C. difficile disease. Toxin EIAs provide good clinical specificity in symptomatic patients, but they are not sensitive enough to rule out C. difficile infection, and presence of toxins does not correlate with true C. difficile infection if asymptomatic carries or cured patients are tested. While NATs offer the excellent sensitivity to detect toxigenic C. difficile, they can detect patients colonized with C. difficile with no toxin production and may lead to overdiagnosis and overtreatment of C. difficile infection. Regardless of the testing method employed, improvement in test utilization is critically important for identification of true C. difficile cases. Institutional agreement on appropriate patient selection for C. difficile testing is needed to prevent negative consequences from detection of colonized C. difficile, such as falsely high C. difficile rates in hospitals and increased colonization and infection with multidrug resistant organisms in patients who received unnecessary antibiotic treatment for C. difficile. Multistep algorithms combining two or three assays can increase diagnostic accuracy of C. difficile infection and are recommended, especially when there are no institutional criteria for patient stool submission. The best performing diagnostic algorithm may differ in each institution, depending on test volume, patient population, laboratory work flow, and cost. Ultrasensitive immunoassays for toxins A and B have potential for stand-alone diagnostic testing for C. difficile pending further validation and accumulation of data.

• #12 Clostridioides (Clostridium) Difficile Colitis Workup: Approach Considerations, Stool Examination and Stool Assays, Endoscopy

  https://emedicine.medscape.com/article/186458-workup

  Stool cultures are the most sensitive tests for detecting C difficile and its toxins. Moreover, results of the stool cultures followed by the identification of a toxigenic culture from an experienced laboratory are the standard used for comparison with other diagnostic testing. […] However, despite their role as the gold standard test in patients with suspected C difficile infection (CDI), stool cultures have a long turnaround time and are resource intensive. Such factors make them too slow for practical clinical decision making (to treat or not to treat) in affected patients. Consequently, in clinical practice, enzyme immunoassay (EIA) for C difficile toxin A and B is used more often. […] However, although EIA is a rapid test for C difficile toxin A and B, it is not an ideal alternative test for diagnosing CDI, due to it having a lesser sensitivity than the cell cytotoxin assay.

• #13 Clostridioides difficile infection – Wikipedia

  https://en.wikipedia.org/wiki/Clostridioides_difficile_infection

  Diagnostic method Stool culture, testing for the bacteria’s DNA or toxins. […] Diagnosis is by stool culture or testing for the bacteria’s DNA or toxins. […] This test is not 100% accurate, with a considerable false-negative rate even with repeat testing. […] Toxigenic culture, in which organisms are cultured on selective media and tested for toxin production, remains the gold standard and is the most sensitive and specific test, although it is slow and labor-intensive. […] Assessment of the A and B toxins by enzyme-linked immunosorbent assay (ELISA) for toxin A or B (or both) has a sensitivity of 63-99% and a specificity of 93-100%, depending on detection assays. […] Testing of stool samples by real-time polymerase chain reaction is able to detect C. difficile about 93% of the time and when positive is incorrectly positive about 3% of the time.

• #14 Clostridioides (Clostridium) Difficile Colitis Workup: Approach Considerations, Stool Examination and Stool Assays, Endoscopy

  https://emedicine.medscape.com/article/186458-workup

  Stool cultures are the most sensitive tests for detecting C difficile and its toxins. Moreover, results of the stool cultures followed by the identification of a toxigenic culture from an experienced laboratory are the standard used for comparison with other diagnostic testing. […] However, despite their role as the gold standard test in patients with suspected C difficile infection (CDI), stool cultures have a long turnaround time and are resource intensive. Such factors make them too slow for practical clinical decision making (to treat or not to treat) in affected patients. Consequently, in clinical practice, enzyme immunoassay (EIA) for C difficile toxin A and B is used more often. […] However, although EIA is a rapid test for C difficile toxin A and B, it is not an ideal alternative test for diagnosing CDI, due to it having a lesser sensitivity than the cell cytotoxin assay.

• #15 Laboratory diagnosis of Clostridioides difficile infection: guidelines and status of practice in Korea – Annals of Clinical Microbiology

  https://www.acm.or.kr/2701-02/

  Clinical laboratories typically use four methods to diagnose CDI: C. difficile culture, toxin detection using immunoassays, GDH detection using immunoassays, and toxin A/B gene detection. […] The detection of GDH, an antigen secreted by C. difficile, can be used as a surrogate marker for the presence or absence of C. difficile strains and as a screening test because of its high sensitivity, although its specificity for toxin-producing strains is low. […] Several commercialized NAATs, including PCR, have been developed and used to detect toxin A and B genes (tcdA and tcdB). […] Guidelines for the diagnosis of CDI have been published by several organizations and countries, most by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA), and the American College of Gastroenterology (ACG).

• #16 Clinical Testing and Diagnosis for CDI | C. diff | CDC

  https://www.cdc.gov/c-diff/hcp/diagnosis-testing/index.html

  Tissue culture cytotoxicity assay only detects toxin B. […] It does provide specific and sensitive results for CDI. […] Although a historical gold standard for diagnosing disease caused by C. diff, this assay is less sensitive than PCR or toxigenic culture for patients with diarrhea. […] Enzyme immunoassay detects toxin A, toxin B, or both A and B. […] However, there are increasing concerns about their relative insensitivity (less than tissue culture cytotoxicity and PCR or toxigenic culture). […] C. diff toxin is very unstable. […] False-negative results occur when specimens are not tested promptly or kept refrigerated until testing. […] This is the most sensitive test available and is most often associated with false-positive results because of the presence of nontoxigenic C. diff strains. […] However, testing isolates for toxin production like so-called „toxigenic culture” helps to reduce false positive results. […] Results of toxigenic cultures serve as a gold standard compared to other test modalities in clinical trials of performance.

• #17 Clostridioides (Clostridium) Difficile Colitis Workup: Approach Considerations, Stool Examination and Stool Assays, Endoscopy

  https://emedicine.medscape.com/article/186458-workup

  The following are stool assays for C difficile, from the most sensitive to the least sensitive: Stool culture is the most sensitive (sensitivity 90-100% and specificity 84-100%), but results are slow and may lead to delay in diagnosis if used alone. […] GDH EIA is very sensitive (sensitivity 85-100% and specificity 87-98%); this test detects the presence of GDH produced by C difficile; positive test results need to be rerun by another assay to verify. […] Real-time PCR assay may be used to detect C difficile gene toxin as an alternative gold standard to stool culture, with some studies demonstrating excellent sensitivity and specificity, as well as test-retest reliability; in a study that used toxigenic culture as the gold standard, the sensitivity was 86%, the specificity was 97%, the positive predictive value (PPV) was 90%, and the negative predictive value (NPV) was 96%, for C difficile.

• #18

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/

  The primary virulence factors in pathogenesis of C. difficile infection are toxins A and B. CCCNA has been considered as a reference method for detecting C. difficile toxin. However, as discussed above, CCCNA is labor intensive, time consuming, requires technical expertise and maintenance of tissue culture facilities. Therefore, rapid enzyme immunoassays (EIAs) to detect toxin A and/or toxin B were the mainstay of C. difficile diagnostic tests for many years. Toxin EIAs are available in multiple formats including solid phase microwell, rapid immunoassays in chromatographic cassettes, immunocard, lateral flow membrane, and automated systems using an enzyme-linked fluorescent assay (ELFA) or a chemiluminescent immunoassay (CLIA). Although several C. difficile toxin EIAs are commercially available, they are all limited in sensitivities and variability within the assays (sensitivities range 44-99% when compared with CCCNA, and 29-88% when compared with TC). The meta-analysis of the studies published from 2009 until June 2014 to evaluate commercial toxin EIA assays compared with a reference method showed pooled sensitivities of 83 and 57% when compared with CCCNA and TC, respectively. Given inadequate performance, professional societies do not recommend toxin EIAs as stand-alone tests for the diagnosis of C. difficile.

• #19 Clostridioides (formerly Clostridium) difficile–Induced Diarrhea – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/anaerobic-bacteria/clostridioides-formerly-clostridium-difficile-induced-diarrhea

  Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Diagnosis is by identifying C. difficile toxin in stool. […] Diagnosis of Clostridioides difficile Induced Diarrhea […] Stool assay for glutamate dehydrogenase (GDH) antigen and C. difficile toxin and polymerase chain reaction (PCR) test for the toxin gene. […] C. difficile induced diarrhea should be suspected in any patient who develops diarrhea within 2 months of antibiotic use or 72 hours of hospital admission. […] Glutamate dehydrogenase (GDH) antigen is produced by all C. difficile strains. Enzyme-linked immunosorbent assay (ELISA) testing for the antigen is sensitive and can be done very quickly. However, a positive test indicates only presence of the organism not whether it is toxigenic.

• #20 Clostridioides difficile Infection: Update on Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/0201/p168.html

  The EIA for GDH has high sensitivity, which makes it a useful screening test because a negative result essentially rules out infection (negative predictive value = 94% to 100%). […] The EIA for toxins A and B has the highest specificity, whereas NAAT is both sensitive and specific. […] The choice of diagnostic test depends on local preference, financial constraints, and volume of samples tested each day. […] Repeat testing within seven days during the same episode of diarrhea is not recommended because the high sensitivity of the tests can lead to false-positive results.

• #21

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/

  The primary virulence factors in pathogenesis of C. difficile infection are toxins A and B. CCCNA has been considered as a reference method for detecting C. difficile toxin. However, as discussed above, CCCNA is labor intensive, time consuming, requires technical expertise and maintenance of tissue culture facilities. Therefore, rapid enzyme immunoassays (EIAs) to detect toxin A and/or toxin B were the mainstay of C. difficile diagnostic tests for many years. Toxin EIAs are available in multiple formats including solid phase microwell, rapid immunoassays in chromatographic cassettes, immunocard, lateral flow membrane, and automated systems using an enzyme-linked fluorescent assay (ELFA) or a chemiluminescent immunoassay (CLIA). Although several C. difficile toxin EIAs are commercially available, they are all limited in sensitivities and variability within the assays (sensitivities range 44-99% when compared with CCCNA, and 29-88% when compared with TC). The meta-analysis of the studies published from 2009 until June 2014 to evaluate commercial toxin EIA assays compared with a reference method showed pooled sensitivities of 83 and 57% when compared with CCCNA and TC, respectively. Given inadequate performance, professional societies do not recommend toxin EIAs as stand-alone tests for the diagnosis of C. difficile.

• #22 Clostridioides difficile – Antigen, PCR, Susceptibility, and Typing | Public Health Ontario

  https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Clostridium-difficile

  C. difficile virulence typing is performed by laboratory-developed cdtB (binary toxin subunit B), tcdA (toxin A), tcdB (toxin B), and tpi (triose phosphate isomerase) PCR testing on the isolate at PHO. […] C. difficile cluster subtyping is performed by whole genome sequencing (WGS) using a research use protocol. […] GDH antigen testing evaluates the potential presence of C. difficile bacteria in feces. It has a reported sensitivity of 94-96% and specificity of 92-95% compared with reference methods (e.g., cell cytotoxin assay or cytotoxigenic culture). […] Negative results usually rule out CDI but positive results may represent nontoxigenic C. difficile excretion and therefore require confirmation with either toxin antigen testing or toxin gene PCR testing. […] Toxin antigen testing evaluates the presence of toxin A and/or B in feces but does not distinguish between the two toxins. It has a reported sensitivity of 58-83% and specificity of 99% compared with reference methods.

• #23 Diagnosis and Treatment of Clostridium difficile in Adults: A Systematic Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6561347/

  Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased. […] We reviewed current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age 18 years). […] Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C. difficile. […] Diagnostic approaches are complex due to the availability of multiple testing strategies. […] Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single step PCR on liquid stool samples have the best test performance characteristics (multistep: sensitivity 0.68 to 1.00 / specificity 0.92 to 1.00; single step: sensitivity 0.860.92 / specificity 0.940.97). […] Diagnostic testing for CDI should be performed only in symptomatic patients.

• #24 C. difficile FAQs

  https://www.cepheid.com/en-US/solutions/cdifficile-faqs.html

  Molecular tests/NAATs are designed to detect DNA from Clostridium difficile organisms capable of producing toxin (also referred to as toxigenic C. difficile) found in stool. PCR is one type of NAAT. The sensitivity of detection of toxigenic C. difficile organism by GeneXpert has been reported to be 9499% and correlated well with a clinical diagnosis of C. difficile infection (CDI). […] The first step is to determine if the patients sample contains toxigenic C. difficile. Patients positive for toxigenic C. difficile constitute an infection control risk, and can transmit disease to other patients. Once a patient with toxigenic C. difficile has been identified and appropriate infection control measures have been implemented, the next step is to determine if the patient has CDI and requires treatment.

• #25 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA

  https://www.idsociety.org/practice-guideline/clostridium-difficile/

  A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. […] CDI is defined by the presence of symptoms (usually diarrhea) and either a stool test positive for C. difficile toxins or detection of toxigenic C. difficile, or colonoscopic or histopathologic findings revealing pseudomembranous colitis. […] Patients with unexplained and new-onset 3 unformed stools in 24 hours are the preferred target population for testing for CDI. […] Use a stool toxin test as part of a multistep algorithm (ie, glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no preagreed institutional criteria for patient stool submission.

• #26 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA

  https://www.idsociety.org/practice-guideline/clostridium-difficile/

  Use a NAAT alone or a multistep algorithm for testing (ie, GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than a toxin test alone when there are preagreed institutional criteria for patient stool submission. […] Do not perform repeat testing (within 7 days) during the same episode of diarrhea and do not test stool from asymptomatic patients, except for epidemiological studies. […] There are insufficient data to recommend use of biologic markers as an adjunct to diagnosis. […] Because of the high prevalence of asymptomatic carriage of toxigenic C. difficile in infants, testing for CDI should never be routinely recommended for neonates or infants 12 months of age with diarrhea. […] C. difficile testing should not be routinely performed in children with diarrhea who are 12 years of age unless other infectious or noninfectious causes have been excluded. […] In children 2 years of age, C. difficile testing is recommended for patients with prolonged or worsening diarrhea and risk factors (eg, underlying inflammatory bowel disease or immunocompromising conditions) or relevant exposures (eg, contact with the healthcare system or recent antibiotics).

• #27 Biliary Tract Disorders, Gallbladder Disorders, & Gallstone Pancreatitis | ACG

  https://gi.org/topics/c-difficile-infection/

  C. Difficile Infection (CDI) Overview […] The diagnosis of C. difficile should be considered in patients with new and unexplained diarrhea occurring more than 3 times per day. The diagnosis is confirmed based on stool testing. There are several stool tests that can be used to diagnose C. difficile infections. The following 3 tests are commonly used: GDH, Toxin EIA and Toxin B PCR. It is now recommended that a 2 step testing algorithm be used to confirm the diagnosis of C. difficile, where GDH or Toxin B PCR is used as a screening test and the Toxin EIA is used to confirm the diagnosis. Your physician can order these tests at most commercial labs. […] The current guidelines separate C. difficile infection into 3 categories: non-severe, severe and fulminant.

• #28 Clostridium difficile Toxin/GDH With Reflex to PCR | Test Summary | Quest Diagnostics Clostridium difficile Toxin/GDH with Reflex to PCRClostridium difficile Toxin/GDH with Reflex to PCR

  https://testdirectory.questdiagnostics.com/test/test-guides/TS_Cdiff_Toxin_GDH/clostridium-difficile-toxingdh-with-reflex-to-pcr

  Immunoassay that simultaneously detects toxins A and B and GDH in a single assay. […] Real-time PCR targeting the C difficile toxin B gene if toxin and GDH results are discordant. […] Absence of both GDH antigen and toxin is consistent with absence of C difficile infection. […] Presence of both GDH antigen and toxin is consistent with C difficile infection in a symptomatic patient. […] Presence of either GDH antigen or toxin, coupled with presence of C difficile toxin B gene (ie, positive PCR test), is consistent with C difficile infection in a symptomatic patient. […] Presence of GDH antigen and absence of both toxin and C difficile toxin B gene (ie, negative PCR test) is consistent with presence of a non–disease-causing strain of C difficile or another Clostridioides species.

• #29 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA

  https://www.idsociety.org/practice-guideline/clostridium-difficile/

  Use a NAAT alone or a multistep algorithm for testing (ie, GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than a toxin test alone when there are preagreed institutional criteria for patient stool submission. […] Do not perform repeat testing (within 7 days) during the same episode of diarrhea and do not test stool from asymptomatic patients, except for epidemiological studies. […] There are insufficient data to recommend use of biologic markers as an adjunct to diagnosis. […] Because of the high prevalence of asymptomatic carriage of toxigenic C. difficile in infants, testing for CDI should never be routinely recommended for neonates or infants 12 months of age with diarrhea. […] C. difficile testing should not be routinely performed in children with diarrhea who are 12 years of age unless other infectious or noninfectious causes have been excluded. […] In children 2 years of age, C. difficile testing is recommended for patients with prolonged or worsening diarrhea and risk factors (eg, underlying inflammatory bowel disease or immunocompromising conditions) or relevant exposures (eg, contact with the healthcare system or recent antibiotics).

• #30

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/

  Currently, there is no FDA-approved single rapid test that can be reliably used to diagnose C. difficile disease. Toxin EIAs provide good clinical specificity in symptomatic patients, but they are not sensitive enough to rule out C. difficile infection, and presence of toxins does not correlate with true C. difficile infection if asymptomatic carries or cured patients are tested. While NATs offer the excellent sensitivity to detect toxigenic C. difficile, they can detect patients colonized with C. difficile with no toxin production and may lead to overdiagnosis and overtreatment of C. difficile infection. Regardless of the testing method employed, improvement in test utilization is critically important for identification of true C. difficile cases. Institutional agreement on appropriate patient selection for C. difficile testing is needed to prevent negative consequences from detection of colonized C. difficile, such as falsely high C. difficile rates in hospitals and increased colonization and infection with multidrug resistant organisms in patients who received unnecessary antibiotic treatment for C. difficile. Multistep algorithms combining two or three assays can increase diagnostic accuracy of C. difficile infection and are recommended, especially when there are no institutional criteria for patient stool submission. The best performing diagnostic algorithm may differ in each institution, depending on test volume, patient population, laboratory work flow, and cost. Ultrasensitive immunoassays for toxins A and B have potential for stand-alone diagnostic testing for C. difficile pending further validation and accumulation of data.

• #31 Diagnosing Clostridium Difficile Infections | NYU Langone Health

  https://nyulangone.org/conditions/clostridium-difficile-infections/diagnosis

  Infections with Clostridium difficile typically occur in people taking antibiotics or those who have recently taken them. […] To diagnose a C. difficile infection, your NYU Langone doctor takes a medical history and asks about any medications you are taking. He or she may also order one or several tests, depending on your symptoms, medical history, and whether you are currently in a hospital or healthcare facility or have recently been released from one. […] The simplest way to detect C. difficile is through a stool test, in which you provide a sample in a sterile container given to you at your doctors office or a lab. A pathologist, a doctor who studies diseases in a laboratory, determines whether the sample has signs of C. difficile. […] A blood test can reveal high levels of white blood cells, a sign of infection. Very high levels can signify a more severe C. difficile infection, in which a person may have watery diarrhea, intense stomach cramps, and dehydration.

• #32 Diagnosing Clostridium Difficile Infections | NYU Langone Health

  https://nyulangone.org/conditions/clostridium-difficile-infections/diagnosis

  If you have severe symptoms of C. difficile, a doctor may examine the colon using a colonoscopy or sigmoidoscopy. […] These tests can indicate whether inflammation is present, indicating a C. difficile infection. They also allow a doctor to take tissue samples, if necessary, to further test for infection. […] If a doctor suspects you have a complication of C. difficile infection, such as a hole in the intestines, he or she may order a CT scan.

• #33 Diagnosis and Treatment of Clostridium difficile in Adults: A Systematic Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6561347/

  The definitive gold standard for CDI is detection of toxigenic C. difficile in stool along with colonic histopathology showing pseudomembranes in a patient with clinical symptoms. […] Many laboratories will only test diarrheal stool for C. difficile. […] Given the suboptimal sensitivity of some toxin EIA kits combined with increased detection of asymptomatic colonization with single-step algorithms (NAAT), many experts and some guidelines have advocated approaches that use multiple tests (multistep algorithms) for rapid diagnosis. […] Guidelines recommend that CDI should be treated according to disease severity, and risk of recurrence or complications. […] The 2010 Society for Healthcare Epidemiology of America and Infectious Disease Society of America Clinical Practice Guidelines categorize mild CDI as WBC 15 X 109/L and serum creatinine 1.5 times premorbid level; severe CDI as WBC 15 X 109/L, or serum creatinine 1.5 times premorbid level; and severe, complicated CDI as hypotension or shock, ileus, or megacolon.

• #34 C. difficile infection – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/c-difficile/diagnosis-treatment/drc-20351697

  A diagnosis of C. difficile infection is based on having: […] C. difficile in a stool sample. […] If C. difficile infection is suspected, one or more tests of a stool sample can show either the toxins or strains of the bacteria that produce toxins. […] Rarely, to help confirm a diagnosis of C. difficile infection, a health care provider might check the inside of the colon. […] An X-ray of the stomach area or a CT scan can look for possible complications of C. difficile infection.

• #35 Clostridioides Difficile: Nursing Diagnoses, Care Plans, Assessment & Interventions | NurseTogether

  https://www.nursetogether.com/clostridioides-difficile-c-diff-nursing-diagnosis-care-plan/

  Polymerase chain reaction (PCR) is a recent technique for finding the toxin genes. It is the most accurate and precise test. Results are available in one hour and only require one stool sample. […] Stool culture is the most sensitive test, but the results may take days which may cause delays in the diagnosis and treatment of C. difficile. […] If the healthcare provider suspects potential complications of C. difficile, an abdominal X-ray or a computed tomography (CT) scan should be considered. It reveals images of the colon, showing bowel inflammation due to C. difficile infection. The scan identifies conditions such as bowel enlargement, bowel perforation, increasing colon wall thickness, and toxic megacolon.

• #36 Clostridioides difficile infection – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/clostridioides-difficile-infection/

  Diagnosis of symptomatic patients is based on stool tests for CDI, which detect toxins or toxigenic strains of C. difficile or the identification of pseudomembranous colitis on imaging or endoscopy. […] The diagnosis of CDI is based on the presence of typical clinical features (especially in patients with risk factors for CDI) and either of the following: C. difficile toxins or toxigenic strains of C.difficile detected on stool tests for CDI or pseudomembranous colitis confirmed on endoscopy or histopathology. […] Patient history and clinical presentation can provide strong indicators for infection, which should be confirmed by stool studies, colonoscopy, or histopathology findings. […] Initial tests: stool analysis for toxins and toxigenic strains of C. difficile. […] Consider a multi-test algorithmic approach guided by the pretest probability (PTP) of CDI.

• #37 Clostridioides difficile infection – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/clostridioides-difficile-infection/

  The initial test should preferably be a high sensitivity test (i.e., NAAT or EIA for GDH). […] Negative NAAT or EIA for GDH: CDI is ruled out. […] Positive NAAT or EIA for GDH: Confirm CDI using a highly specific test, such as EIA for C. difficile toxins. […] Repeat testing within 7 days of diarrhea is not recommended, and asymptomatic individuals should not be tested. […] Consider if the diagnosis remains unclear after initial tests. […] Consider if the PTP of CDI remains high in patients with insufficient response to empirical antibiotic therapy for CDI.

• #38 Diagnosis and Treatment of Clostridium difficile in Adults: A Systematic Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6561347/

  The definitive gold standard for CDI is detection of toxigenic C. difficile in stool along with colonic histopathology showing pseudomembranes in a patient with clinical symptoms. […] Many laboratories will only test diarrheal stool for C. difficile. […] Given the suboptimal sensitivity of some toxin EIA kits combined with increased detection of asymptomatic colonization with single-step algorithms (NAAT), many experts and some guidelines have advocated approaches that use multiple tests (multistep algorithms) for rapid diagnosis. […] Guidelines recommend that CDI should be treated according to disease severity, and risk of recurrence or complications. […] The 2010 Society for Healthcare Epidemiology of America and Infectious Disease Society of America Clinical Practice Guidelines categorize mild CDI as WBC 15 X 109/L and serum creatinine 1.5 times premorbid level; severe CDI as WBC 15 X 109/L, or serum creatinine 1.5 times premorbid level; and severe, complicated CDI as hypotension or shock, ileus, or megacolon.

• #39 Diagnosis and Treatment of Clostridium difficile in Adults: A Systematic Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6561347/

  Treatment strategies should be based on disease severity, history of prior CDI, and the individual patients risk of recurrence. […] Vancomycin is the treatment of choice for severe or complicated CDI, with or without other adjunctive therapies. […] Metronidazole is appropriate for mild disease. […] Fidaxomicin is a therapeutic option for those with recurrent CDI or a high risk of recurrence. […] Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established. […] The diagnosis of CDI requires: 1) presence of diarrhea, defined as three or more unformed stools in 24-hours, and 2) positive stool test for toxigenic C. difficile or its toxins, or colonoscopic/histopathologic findings demonstrating pseudomembranous colitis.

• #40 C. diff Infection: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/15548-c-diff-infection

  Antibiotics to treat C. diff include: Metronidazole, Vancomycin, Fidaxomicin. […] If you have severe complications, you might need intensive care. In rare cases, providers recommend emergency surgery to remove the source of the infection in your colon. This is called colectomy. […] If your healthcare provider suspects C. diff infection based on your symptoms, they’ll take a sample of your poop and send it to a lab. The lab will test it for C. diff toxins.

• #41

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/

  Clostridium (reclassified as Clostridioides) difficile is an anaerobic, gram-positive bacterium that causes significant disease through elaboration of two potent toxins in patients whose normal gut microbiota has been altered through antimicrobial or chemotherapeutic agents (dysbiosis). The optimum method of laboratory diagnosis is still somewhat controversial. Recent practice guidelines published by professional societies recommend a two-step approach beginning with a test for glutamate dehydrogenase (GDH), followed by a toxin test and/or a nucleic acid test. Alternately, in institutions where established clinical algorithms guide testing, a nucleic acid test alone is acceptable. Nucleic acid tests are the methods of choice in approximately 50% of laboratories in the United States. These tests are considered as the most sensitive methods for detection of C. difficile in stool and are the least specific. Because of the lower specificity with nucleic acid tests, some clinicians believe that toxin enzyme immunoassays are better predictors of disease, despite their known poor performance in certain patient populations. This review will discuss the advantages and disadvantages of the currently available test methods for the diagnosis of C. difficile with a brief mention of some novel assays that are currently in clinical trials.

• #42 Diagnosing C. diff Infections for Optimal Patient Outcomes

  https://asm.org/articles/2019/november/diagnosing-c-diff-infections-for-optimal-patient-o

  Clostridioides difficile, better known as C. diff, is large problem. C. diff is 1 of 5 microorganisms on the Center for Disease Control and Prevention (CDC)’s Urgent Threat List, the top category of antibiotic-resistant threats to human health. […] This makes November a great time to highlight the many research efforts going into not only treating but also diagnosing this terrible disease. […] Kraft is the lead author of a recent meta-analysis study on best diagnostic tests for C. diff infection. […] The biggest challenge is that in our field of clinical microbiology, we tend to do comparison studies that compare the sensitivity, specificity, and negative and positive predictive values which can be grouped as diagnostic accuracy. […] One of the things that has led us as a field to worry about how were diagnosing C. difficile diarrhea is one of the tests, called a nucleic acid amplification test or PCR.

• #43 Diagnosing C. diff Infections for Optimal Patient Outcomes

  https://asm.org/articles/2019/november/diagnosing-c-diff-infections-for-optimal-patient-o

  This result has contributed to the issue of overdiagnosis of C. diff: people may be colonized, may not be having symptoms from it, but for some reason they get their stool tested and it shows that they have C. diff, so they get treated for it. […] Another test that we looked at was the enzyme immunoassay (EIA) test for toxin. […] The other test we looked at was only in algorithm or in combination with the other tests, and that was the GDH test, which tests for an enzyme. […] We found that any algorithm that contains C. diff PCR was a good test. […] We did not have enough literature to make the statement that PCR alone is sufficient for C. diff diagnosis, so at the step we can only say that any of them can be used. […] What I really want to come after this manuscript tis that people start to do studies that are relevant to the diagnosis of diseases from a clinical outcome standpoint and not just based on the diagnostic accuracy of the test itself. […] If we can motivate others to produce quality evidence to support testing and diagnosis of certain infections, thats the goal of the manuscript.

• #44

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/

  Currently, there is no FDA-approved single rapid test that can be reliably used to diagnose C. difficile disease. Toxin EIAs provide good clinical specificity in symptomatic patients, but they are not sensitive enough to rule out C. difficile infection, and presence of toxins does not correlate with true C. difficile infection if asymptomatic carries or cured patients are tested. While NATs offer the excellent sensitivity to detect toxigenic C. difficile, they can detect patients colonized with C. difficile with no toxin production and may lead to overdiagnosis and overtreatment of C. difficile infection. Regardless of the testing method employed, improvement in test utilization is critically important for identification of true C. difficile cases. Institutional agreement on appropriate patient selection for C. difficile testing is needed to prevent negative consequences from detection of colonized C. difficile, such as falsely high C. difficile rates in hospitals and increased colonization and infection with multidrug resistant organisms in patients who received unnecessary antibiotic treatment for C. difficile. Multistep algorithms combining two or three assays can increase diagnostic accuracy of C. difficile infection and are recommended, especially when there are no institutional criteria for patient stool submission. The best performing diagnostic algorithm may differ in each institution, depending on test volume, patient population, laboratory work flow, and cost. Ultrasensitive immunoassays for toxins A and B have potential for stand-alone diagnostic testing for C. difficile pending further validation and accumulation of data.

• #45 Laboratory diagnosis of Clostridioides difficile infection: guidelines and status of practice in Korea – Annals of Clinical Microbiology

  https://www.acm.or.kr/2701-02/

  The consensus is that standalone testing is not appropriate in most cases and is not recommended. However, the IDSA guidelines note that NAAT alone can be tested if there are institutional criteria for specimen submission. All guidelines recommend a multistep algorithm. Each test has strengths and weaknesses, and no one test is perfect; therefore, a combination of two or more tests should be used to diagnose CDI. […] Because each CDI diagnostic test has its strengths and limitations, varies in performance, and no single test is perfect, many guidelines recommend combining tests or using multistep algorithms. Guidelines for CDI diagnosis have been developed by organizations, such as ESCMID, IDSA/SHEA, and ACG, and other countries have guidelines.

• #46 C. difficile FAQs

  https://www.cepheid.com/en-US/solutions/cdifficile-faqs.html

  A: Some published studies have shown that patients with toxin-positive stool samples had worse outcomes than patients with samples negative for toxin. However, another study showed that among PCR-positive samples, the outcomes of patients with toxin-positive stools and toxin-negative stools were similar. […] A: No, not all patients testing positive for C. difficile with PCR-based assays should be treated. Only patients who meet the clinical criteria for CDI should be treated; patients who test positive by PCR who do not meet those criteria may be colonized. […] A: A recent study and accompanying editorial suggested that the use of molecular tests for the diagnosis of CDI was likely to result in overtreatment. […] A: An initial increase in positive results is expected, but this should subsequently decline as improved case detection reduces rates of transmission.

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