Clostridium difficile Toxin/GDH With Reflex to PCR
Clostridium difficile Toxin/GDH With Reflex to PCR
This test is used to diagnose C difficile infection in symptomatic patients.
Test Summary
Clostridium difficile Toxin/GDH With Reflex to PCR
Test code: 91664
Clinical use
- Diagnose Clostridium difficile infection in symptomatic patients
Clinical background
C difficile (genus recently reclassified to Clostridioides1,2) is an opportunistic, toxin-producing bacterial pathogen of the gastrointestinal (GI) tract. As the most common cause of healthcare-acquired infection and hospital-acquired diarrhea in the United States,3 C difficile places substantial burden on the healthcare system, causing nearly half a million infections and contributing to over 20,000 deaths annually.4 Although the incidence of healthcare-acquired C difficile infection has decreased over the past decade, the incidence of community-acquired infection has increased,5 and C difficile remains an urgent public health threat.6
C difficile commonly colonizes the GI tract of healthy individuals (5% of adults and 15% to 70% of infants7). It becomes problematic when antibiotic therapy alters the intestinal flora, facilitating its proliferation.7 C difficile infection can result in GI problems ranging from mild diarrhea to life-threatening fulminant colitis.7
Disease-causing C difficile produces toxins (A and/or B) that cause the destruction of intestinal epithelial cells.7 A C difficile strain called ribotype 027/NAP1/BI, which emerged in the early 2000s, expresses a variant of toxin B that makes the strain more virulent than those previously identified.7 Toxins are detected by immunoassay, which has high specificity (99%) but relatively low sensitivity (57% to 83%).2,3
C difficile also produces a large amount of glutamate dehydrogenase (GDH). Diagnostic tests that detect GDH are therefore highly sensitive for C difficile (94% to 96%).2,3 However, because GDH is produced by toxigenic and non-toxigenic C difficile strains, these tests have low specificity for disease-causing C difficile.2,3
Because no single test has the combined sensitivity and specificity required to unambiguously identify disease-causing C difficile,2,3 guidelines recommend a multistep testing algorithm: toxin A and B testing combined with GDH testing and/or toxin gene testing (using nucleic acid amplification tests such as polymerase chain reaction [PCR] assays).2,3,8
Quest Diagnostics offers the Clostridium difficile Toxin/GDH With Reflex to PCR test (test code 91664), an immunoassay that simultaneously detects toxins A and B and GDH and reflexes to real-time PCR targeting the C difficile toxin B gene (tcdB) if results are discordant.
Individuals suitable for testing
- Individuals with unexplained unformed stool
- Individuals with suspected ileus due to C difficile infection
Testing is not recommended for infants <1 year old.3 Testing for cure is discouraged,2,3 as is repeat testing, except in epidemic settings (eg, in patients with suspected C difficile infection and worsening symptoms).3
Method
- 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
- Analytical sensitivity: 0.63 ng/mL for toxin A, 0.16 ng/mL for toxin B, 0.8 ng/mL for GDH9
Reflex testing is performed at an additional charge.
Interpretive information
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.
References
- Lawson PA, Citron DM, Tyrrell KL, et al. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O’Toole 1935) Prévot 1938. Anaerobe. 2016;40:95-99. doi:10.1016/j.anaerobe.2016.06.008
- Kelly CR, Fischer M, Allegretti JR, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2020;116(6):1124-1147. doi:10.14309/ajg.0000000000001278
- McDonald LC, Gerding DN, Johnson S, et al. 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). Clin Infect Dis. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085
- Guh AY, Mu Y, Winston LG, et al. Trends in U.S. burden of Clostridioides difficile infection and outcomes. New Engl J Medicine. 2020;382(14):1320-1330. doi:10.1056/nejmoa1910215
- Fu Y, Luo Y, Grinspan AM. Epidemiology of community-acquired and recurrent Clostridioides difficile infection. Ther Adv Gastroenterol. 2021;14:17562848211016248. doi:10.1177/17562848211016248
- US Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. Revised December 2019. Accessed July 7, 2023. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf. doi:10.15620/cdc:82532
- Czepiel J, Dróżdż M, Pituch H, et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis. 2019;38(7):1211-1221. doi:10.1007/s10096-019-03539-6
- Kraft CS, Parrott JS, Cornish NE, et al. A laboratory medicine best practices systematic review and meta-analysis of nucleic acid amplification tests (NAATs) and algorithms including NAATs for the diagnosis of Clostridioides (Clostridium) difficile in adults. Clin Microbiol Rev. 2019;32(3):e00032-18. doi:10.1128/cmr.00032-18
- C. Diff Quik Chek Complete®. Package insert. TECHLAB, Inc; 2021. Accessed June 9, 2023. https://www.techlab.com/wp-content/uploads/2021/09/C-DIFF-QUIK-CHEK-COMPLETE-PI-91-525-03-TL-_06-2021.pdf
Content reviewed 07/2023
This test is used to diagnose C difficile infection in symptomatic patients.
Test Summary
Clostridium difficile Toxin/GDH With Reflex to PCR
Test code: 91664
Clinical use
- Diagnose Clostridium difficile infection in symptomatic patients
Clinical background
C difficile (genus recently reclassified to Clostridioides1,2) is an opportunistic, toxin-producing bacterial pathogen of the gastrointestinal (GI) tract. As the most common cause of healthcare-acquired infection and hospital-acquired diarrhea in the United States,3 C difficile places substantial burden on the healthcare system, causing nearly half a million infections and contributing to over 20,000 deaths annually.4 Although the incidence of healthcare-acquired C difficile infection has decreased over the past decade, the incidence of community-acquired infection has increased,5 and C difficile remains an urgent public health threat.6
C difficile commonly colonizes the GI tract of healthy individuals (5% of adults and 15% to 70% of infants7). It becomes problematic when antibiotic therapy alters the intestinal flora, facilitating its proliferation.7 C difficile infection can result in GI problems ranging from mild diarrhea to life-threatening fulminant colitis.7
Disease-causing C difficile produces toxins (A and/or B) that cause the destruction of intestinal epithelial cells.7 A C difficile strain called ribotype 027/NAP1/BI, which emerged in the early 2000s, expresses a variant of toxin B that makes the strain more virulent than those previously identified.7 Toxins are detected by immunoassay, which has high specificity (99%) but relatively low sensitivity (57% to 83%).2,3
C difficile also produces a large amount of glutamate dehydrogenase (GDH). Diagnostic tests that detect GDH are therefore highly sensitive for C difficile (94% to 96%).2,3 However, because GDH is produced by toxigenic and non-toxigenic C difficile strains, these tests have low specificity for disease-causing C difficile.2,3
Because no single test has the combined sensitivity and specificity required to unambiguously identify disease-causing C difficile,2,3 guidelines recommend a multistep testing algorithm: toxin A and B testing combined with GDH testing and/or toxin gene testing (using nucleic acid amplification tests such as polymerase chain reaction [PCR] assays).2,3,8
Quest Diagnostics offers the Clostridium difficile Toxin/GDH With Reflex to PCR test (test code 91664), an immunoassay that simultaneously detects toxins A and B and GDH and reflexes to real-time PCR targeting the C difficile toxin B gene (tcdB) if results are discordant.
Individuals suitable for testing
- Individuals with unexplained unformed stool
- Individuals with suspected ileus due to C difficile infection
Testing is not recommended for infants <1 year old.3 Testing for cure is discouraged,2,3 as is repeat testing, except in epidemic settings (eg, in patients with suspected C difficile infection and worsening symptoms).3
Method
- 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
- Analytical sensitivity: 0.63 ng/mL for toxin A, 0.16 ng/mL for toxin B, 0.8 ng/mL for GDH9
Reflex testing is performed at an additional charge.
Interpretive information
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.
References
- Lawson PA, Citron DM, Tyrrell KL, et al. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O’Toole 1935) Prévot 1938. Anaerobe. 2016;40:95-99. doi:10.1016/j.anaerobe.2016.06.008
- Kelly CR, Fischer M, Allegretti JR, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2020;116(6):1124-1147. doi:10.14309/ajg.0000000000001278
- McDonald LC, Gerding DN, Johnson S, et al. 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). Clin Infect Dis. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085
- Guh AY, Mu Y, Winston LG, et al. Trends in U.S. burden of Clostridioides difficile infection and outcomes. New Engl J Medicine. 2020;382(14):1320-1330. doi:10.1056/nejmoa1910215
- Fu Y, Luo Y, Grinspan AM. Epidemiology of community-acquired and recurrent Clostridioides difficile infection. Ther Adv Gastroenterol. 2021;14:17562848211016248. doi:10.1177/17562848211016248
- US Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. Revised December 2019. Accessed July 7, 2023. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf. doi:10.15620/cdc:82532
- Czepiel J, Dróżdż M, Pituch H, et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis. 2019;38(7):1211-1221. doi:10.1007/s10096-019-03539-6
- Kraft CS, Parrott JS, Cornish NE, et al. A laboratory medicine best practices systematic review and meta-analysis of nucleic acid amplification tests (NAATs) and algorithms including NAATs for the diagnosis of Clostridioides (Clostridium) difficile in adults. Clin Microbiol Rev. 2019;32(3):e00032-18. doi:10.1128/cmr.00032-18
- C. Diff Quik Chek Complete®. Package insert. TECHLAB, Inc; 2021. Accessed June 9, 2023. https://www.techlab.com/wp-content/uploads/2021/09/C-DIFF-QUIK-CHEK-COMPLETE-PI-91-525-03-TL-_06-2021.pdf
Content reviewed 07/2023