Clinical Education Center
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- ABL Kinase Domain Mutation in CML, Cell-based
- ABO Group and Rh Type
- Acid-Fast Bacillus (AFB) Identification, Sequencing and Stain, Paraffin Block
- ADAMTS13 Activity with Reflex to ADAMTS13 Inhibitor
- Alcohol Metabolites, Quantitative, Urine
- Alpha-Globin Common Mutation Analysis
- Alpha-Globin Gene Deletion or Duplication
- Alpha-Globin Gene Sequencing
- Anti-Müllerian Hormone AssessR™
- Anti-PF4 and Serotonin Release Assay (SRA) for Diagnosing Heparin-induced Thrombocytopenia/Thrombosis (HIT/HITT)
- Antiphospholipid Antibodies
- ASCVD Risk Panel with Score
- Autoimmune Epilepsy Evaluation
- Autoimmune Diseases, Tests for
- B-cell and T-cell Clonality Assays by PCR
- B-Type Natriuretic Peptide (BNP)
- BCR-ABL1 Gene Rearrangement, Quantitative PCR
- Beta-Globin Complete
- BRCAvantage®, Ashkenazi Jewish Screen
- BRCAvantage®, Rearrangements
- BRCAvantage™, Comprehensive
- BRCAvantage™, Single Site
- CDH1 Sequencing and Deletion/Duplication
- Clostridium difficile Diagnostic Testing
- C1 Inhibitor, Protein and Functional Tests
- Calreticulin (CALR) Mutation Analysis
- Carbapenem Resistant Enterobacteriaceae Culture Screen
- Cardio IQ Lipoprotein Fractionation, Ion Mobility
- Cervical Cancer, TERC, FISH
- CFvantage® Cystic Fibrosis Expanded Screen
- Chlamydia trachomatis, TMA
- Chlamydia trachomatis/Neisseria gonorrhoeae RNA, TMA
- Chromosomal Microarray, POC, ClariSure®, Oligo-SNP
- Chromosomal Microarray, Postnatal, ClariSure® Oligo-SNP
- Chromosome Analysis and AFP with Reflex to AChE, Fetal Hgb, Amniotic Fluid
- Chromosome Analysis, Amniotic Fluid
- Chromosome Analysis, Blood
- Chromosome Analysis, Blood with Reflex to Postnatal, ClariSure® Oligo-SNP Array
- Chromosome Analysis, Chorionic Villus Sample
- Chromosome Analysis, High Resolution
- Chromosome Analysis, High Resolution with Reflex to Postnatal, ClariSure® Oligo-SNP Array
- Chromosome Analysis, Mosaicism
- Chromosome Analysis, Neonatal Blood
- Chromosome Analysis, Sister Chromatid Exchange
- Chromosome Analysis, Tissue
- Chromosome DEB Assay for Fanconi anemia
- Chronic Lymphocytic Leukemia (CLL) - Diagnostic and Prognostic Testing
- Culture, Fungus
- Culture, Urine, Routine
- Cystic Fibrosis Screen
- Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) PCR
- D-Dimer, Quantitative
- Dementia, Secondary Causes
- Dengue Virus Testing
- Diabetes Risk Panel with Score and Cardio IQ® Diabetes Risk Panel with Score
- Drug Testing, General Toxicology (Blood, Urine, or Serum)
- Drug Toxicology Alcohol Metab, QN, Oral Fluid
- Factor V (Leiden) Mutation Analysis
- Familial Mediterranean Fever Mutation Analysis
- First Trimester Screen, hCG
- First Trimester Screen, Hyperglycosylated hCG (h-hCG)
- FISH, Angelman
- FISH, MET Amplification
- FISH, Myeloma, 17p-, rea 14q32 with Reflexes
- FISH, Prader-Willi
- FISH, Prenatal Screen
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- HCV Genotyping
- Helicobacter pylori (H pylori) Antibody Discontinuation
- Heparin, Anti-Xa
- Hepatitis B Surface Antibody, Quantitative
- Hepatitis C Antibody with Reflex to HCV RNA, PCR with Reflex to Genotype
- Hepatitis C Viral RNA Genotype 1 NS5A Drug-resistance
- Hepatitis C Viral RNA Genotype 3 NS5A Drug Resistance
- Hepatitis C Viral RNA NS3 Drug Resistance
- Hepatitis C, RNA, Quantitative, PCR
- Hereditary Cancer Panels: MYvantageTM, QvantageTM, and GIvantageTM
- Hereditary Hemochromatosis DNA Mutation Analysis
- Herpes Simplex Virus (HSV) Type-Specific IgG Antibodies
- Herpes Simplex Virus Type 2 (HSV-2) IgG Inhibition, ELISA
- HIV-1 Coreceptor Tropism, Proviral DNA
- HIV-1 Coreceptor Tropism, Ultradeep Sequencing
- HIV-1 Integrase Genotype
- HIV-1/2 Antigen and Antibodies, Fourth Generation, with Reflexes
- HPV mRNA E6/E7
- Influenza A and B Antigen, Immunoassay
- Influenza Type A and B Antibodies
- Insulin, Intact, LC/MS/MS
- Integrated Screen, Part 1
- Integrated Screen, Part 2
- Intrinsic Factor Blocking Antibody
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- Maternal Serum AFP
- Melanoma, BRAF V600E and V600K Mutation Analysis, THxID®
- Metanephrines, Fractionated, Free, LC/MS/MS, Plasma
- Methylenetetrahydrofolate Reductase (MTHFR), DNA Analysis
- Microalbumin (Urinary Albumin Excretion)
- Pain Management and CYP2D6/CYP2C19
- Pain Management, Naltrexone, Quantitative, Urine
- Partial Thromboplastin Time, Activated (aPTT)
- Penta Screen
- PIK3CA Mutation Analysis
- PNH with FLAER (High Sensitivity)
- Prothrombin Time with INR
- PTH, Intact and Calcium
- Streptococcus pneumoniae (Pneumococcal) Antibody Tests
- Saccharomyces cerevisiae Antibodies (ASCA) (IgG, IgA)
- Sequential Integrated Screen, Part 1
- Sequential Integrated Screen, Part 2
- Serum Integrated Screen, Part 1
- Serum Integrated Screen, Part 2
- Serum Pregnancy Tests
- Sickle Cell Screen
- Stepwise, Part 1
- Stepwise, Part 2
- SureSwab® Trichomonas vaginalis RNA, Qualitative TMA
- SureSwab®, Candidiasis, PCR
- TP53 Sequencing and Deletion/Duplication
- T4, Free
- Tamoxifen and Metabolites, LC-MS/MS
- Testosterone Testing
- Total Testosterone, LC/MS/MS
- Triple Screen
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Clostridium difficile Diagnostic TestingTest code(s) 91664, 16377, 92014, 4408, 34403
Question 1. What is the significance of C difficile in the healthcare setting?
C difficile is an opportunistic, toxin-producing bacterial pathogen of the gastrointestinal tract that is the most common cause of healthcare-associated diarrhea. Infections are commonly seen in patients who have recently been, or are currently being, treated with antibiotics; are elderly; or are in long-term healthcare settings. C difficile causes 25% to 30% of antibiotic-associated diarrhea and >95% of pseudomembranous colitis cases. Incidence has almost doubled since 1996, and the mortality rate is rising owing to emergence of a hypervirulent strain (027/NAP1/B1). In 2011, an estimated one million infections and 29,000 deaths were attributed to C difficile.1
Disease-causing C difficile strains produce 1 or both of 2 toxins: toxin A is an enterotoxin and toxin B is a cytotoxin. Other strains produce neither toxin and are thought to colonize the colon without causing disease.
Question 2. Who should be tested for C difficile infection (CDI)?
Testing should be considered for patients with recent or current antibiotic use, ≥3 episodes of non-formed stool within 24 hours, anorexia, leukocytosis, and no known ileus obstruction. For children ages 1 to 3 with diarrhea, testing can be considered but other causes (eg, viral) should be considered first. Routine testing in children <1 should be avoided given the high carriage rates of C difficile. For children >3, testing considerations are the same as for adults. Although C difficile can colonize neonates/infants, they may lack the cellular machinery to bind and process Clostridium toxins.2
Repeat testing to determine cure is not recommended.
The American College of Gastroenterology3 and the American Society for Microbiology4 guidelines recommend utilizing two different testing options for the detection of C difficile infection:
- Nucleic acid amplification tests (NAAT) for C difficile toxin genes (test code 16377).
- 2- or 3-step algorithm that includes assessment of C difficile toxin and glutamate dehydrogenase (GDH), as well as detection of the C difficile toxin B gene (test code 91664).
The Infectious Disease Society of America/The Society for Healthcare Epidemiology of America (IDSA/SHEA) guidelines, which are posted on the CDC website, recommend gene detection for confirmation when the GDH test is positive and toxin is not detected. They also recommend gene detection when the GDH test is negative and toxin is detected. PCR or another nucleic acid amplification test (NAAT) can be used.1,5
Question 4. How is test code 91664 performed and interpreted?
The first step is an immunoassay to simultaneously assess for toxin and GDH presence. If toxin (either A or B or both) and GDH are present, the specimen is considered positive for toxigenic C difficile infection. If both toxin and GDH are absent, then the specimen is considered negative (Figure 1).
Specimens with discordant results (ie, GDH-positive but toxin-negative or GDH-negative but toxin-positive) proceed to the second step: reflex (at additional charge and additional CPT code) to a PCR C difficile gene detection test. According to our validation studies, discordant results occur in about 6% of cases.
If the gene is detected, results will include genotype information that indicates if the hypervirulent strain (ribotype O27/NAP1/toxinotype III) is present. Table 1 details how the results will be reported and how to interpret them.
The C difficile cytotoxicity assay has served as a historical gold standard for diagnosing clinically significant disease caused by C difficile; however, it is not timely for diagnosis. This assay is best utilized as a reference method or epidemiologic tool.3
Question 6. What are the advantages of newer testing methods?
The newer testing methods are faster than culture and have higher sensitivity and specificity than GDH testing alone. The 2-step analysis algorithm increases the sensitivity to 90.5% and the specificity to 93%.6 The sensitivity of the stand-alone NAAT is 93.4 % and the specificity is 90.9%.7
Question 7. What are the current tests offered by Quest Diagnostics for determination of C difficile infection?
- Clostridium difficile infections. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/hai/organisms/cdiff/cdiff_infect.html. Updated March 1, 2016. Accessed December 1, 2016.
- Schutze GE, Willoughby RE, Committee on Infectious Diseases, American Academy of Pediatrics. Clostridium difficile infection in infants and children. Pediatrics. 2013;131;196-200.
- Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for the diagnosis, treatment and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478-498.
- American Society for Microbiology. A practical guidance document for the laboratory detection of toxigenic Clostridium difficile. https://www.asm.org/images/pdf/Clinical/clostridiumdifficile9-21.pdf. Published September 21, 2010. Accessed December 21, 2016.
- Cohen SH, Gerding DN, Johnson S, et al. 2010. 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). Infect Control Hosp Epidemiol. 2010;31:431-455.
- Package insert TECHLAB® C. DIFF QUIK CHEK COMPLETE®. http://www.alere.com/en/home/product-details/c-diff-quik-chek-complete.html.
- Package insert Xpert® C.difficile/EPI Assay. https://www.cmmc.org/cmmclab/IFU/Xpert_Cdiff_300-9680_Rev_E_Nov12.pdf.
- Chang TW, Gorbach SL, Bartlett JB. Neutralization of Clostridium difficile toxin by Clostridium sordelli antitoxins. Infect Immun. 1978;22:418-422.
- Kyne L, Warny M, Qamar A, et al. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001;357:189-193.
- Aronsson B, Granström M, Möllby R, et al. Serum antibody response to Clostridium difficile toxins in patients with Clostridium difficile diarrhoea. Infection. 1985;13:97-101.
- Giannasca PJ, Warny M. Active and passive immunization against Clostridium difficile diarrhoea and colitis. Vaccine. 2004;22:848-856.
- Johnson S. Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J Infect. 209;58:403-410.
- Kyne L, Warny M, Qamar A, et al. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000;342:390-397.
- Warny M, Vaerman JP, Avesani V, et al. Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect Immun. 1994;62:384-389.
- Viscidi R, Laughon BE, Yolken R, et al. Serum antibody response to toxins A and B of Clostridium difficile. J Infect Dis. 1983;148:93-100.