Beginning today, February 24, 2015, the University of Iowa Hospitals and Clinics Microbiology laboratory will perform C. difficile testing using a two-step algorithm with three components instead of the former PCR test.  The initial screening test will be a combination glutamate dehydrogenase (GDH) and C. difficile toxin antigen assay.

Patients who test GDH positive and toxin negative will be reflexively tested using our current C. difficile PCR.  Because the GDH assay detects nontoxigenic C. difficile, the PCR will determine whether a patient is colonized with toxigenic or nontoxigenic C. difficile.  Clinically, a patient with a GDH-positive, toxin-negative result who is PCR-positive for toxigenic C. difficile is likely to be colonized but not infected by C. difficile, though there is potential for low-level or waxing-and-waning disease (especially under treatment for C. difficile, though no test of cure should be performed).

There were several motivations for this change.

1. There is a high rate of asymptomatic colonization in hospitalized patients [1] that cannot be demonstrated by PCR but can be suggested by the absence of a marker of pathogenesis (C. difficile toxin).  Among PCR-positive patients in a pilot study at UIHC there were 1.5 patients who were toxin negative for every 1 patient who was toxin positive.  It has been demonstrated that patients with a negative toxin antigen test, if left untreated for C. difficile, do not suffer complications of C. difficile disease [2].
2. This algorithm has been shown to be 100% sensitive and 99.6% specific for the diagnosis of C. difficile disease [3].
3. The results for patients who screen negative should be reported more quickly with the GDH/toxin assay.

Key points regarding the new test are as follows:

• Only test diarrheal (i.e., unformed, takes the shape of the container) stool (≥3 loose stools/day for 1 day).  Formed stool will be rejected for testing.
• Nontoxigenic C. difficile does NOT require isolation precautions or treatment.
• Colonizing toxigenic C. difficile can cause infection at a later point in time.
• The presence of toxigenic C. difficile triggers isolation and contact precautions regardless of the clinical interpretation of the result (reviewed in [4]).
• C. difficile results for patients under two years of age should be interpreted with caution due to the high rate of asymptomatic carriage in this population.  The Cepheid Xpert C. difficile/Epi PCR is not FDA-approved for children under two years of age.

[1] F. Alasmari, S. M. Seiler, T. Hink, C.-A. D. Burnham, and E. R. Dubberke, “Prevalence and Risk Factors for Asymptomatic Clostridium difficile Carriage,” Clin. Infect. Dis., p. ciu258, Apr. 2014.

[2] C. R. Polage, D. L. Chin, J. L. Leslie, J. Tang, S. H. Cohen, and J. V. Solnick, “Outcomes in patients tested for Clostridium difficile toxins,” Diagn. Microbiol. Infect. Dis., vol. 74, no. 4, pp. 369–373, Dec. 2012.

[3] S. E. Sharp, L. O. Ruden, J. C. Pohl, P. A. Hatcher, L. M. Jayne, and W. M. Ivie, “Evaluation of the C.Diff Quik Chek Complete Assay, a New Glutamate Dehydrogenase and A/B Toxin Combination Lateral Flow Assay for Use in Rapid, Simple Diagnosis of Clostridium difficile Disease,” J. Clin. Microbiol., vol. 48, no. 6, pp. 2082–2086, Jun. 2010.

[4] A. L. Galdys, S. R. Curry, and L. H. Harrison, “Asymptomatic Clostridium difficile colonization as a reservoir for Clostridium difficile infection,” Expert Rev. Anti Infect. Ther., vol. 12, no. 8, pp. 967–980, May 2014.

Questions concerning this broadcast can be directed to Bradley Ford, MD, PhD, Medical Director of Microbiology; (ext. 6-2990, bradley-ford-1@uiowa.edu).