Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2019 Oct 30;69(10):1667-1674.
doi: 10.1093/cid/ciz009.

Toxin Enzyme Immunoassays Detect Clostridioides difficile Infection With Greater Severity and Higher Recurrence Rates

Alice Y Guh  1 , Kelly M Hatfield  1 , Lisa G Winston  2 , Brittany Martin  3 , Helen Johnston  4 , Geoffrey Brousseau  4 , Monica M Farley  5   6 , Lucy Wilson  7 , Rebecca Perlmutter  7 , Erin C Phipps  8   9 , Ghinwa K Dumyati  10 , Deborah Nelson  10 , Trupti Hatwar  10 , Marion A Kainer  11 , Ashley L Paulick  1 , Maria Karlsson  1 , Dale N Gerding  12   13 , L Clifford McDonald  1
Affiliations
Comparative Study

Toxin Enzyme Immunoassays Detect Clostridioides difficile Infection With Greater Severity and Higher Recurrence Rates

Alice Y Guh et al. Clin Infect Dis. .

Abstract

Background: Few data suggest that Clostridioides difficile infections (CDIs) detected by toxin enzyme immunoassay (EIA) are more severe and have worse outcomes than those detected by nucleic acid amplification tests (NAATs) only. We compared toxin- positive and NAAT-positive-only CDI across geographically diverse sites.

Methods: A case was defined as a positive C. difficile test in a person ≥1 year old with no positive tests in the prior 8 weeks. Cases were detected during 2014-2015 by a testing algorithm (specimens initially tested by glutamate dehydrogenase and toxin EIA; if discordant results, specimens were reflexed to NAAT) and classified as toxin positive or NAAT positive only. Medical charts were reviewed. Multivariable logistic regression models were used to compare CDI-related complications, recurrence, and 30-day mortality between the 2 groups.

Results: Of 4878 cases, 2160 (44.3%) were toxin positive and 2718 (55.7%) were NAAT positive only. More toxin-positive than NAAT-positive-only cases were aged ≥65 years (48.2% vs 38.0%; P < .0001), had ≥3 unformed stools for ≥1 day (43.9% vs 36.6%; P < .0001), and had white blood cell counts ≥15 000 cells/µL (31.4% vs 21.4%; P < .0001). In multivariable analysis, toxin positivity was associated with recurrence (adjusted odds ratio [aOR], 1.89; 95% confidence interval [CI], 1.61-2.23), but not with CDI-related complications (aOR, 0.91; 95% CI, .67-1.23) or 30-day mortality (aOR, 0.95; 95% CI, .73-1.24).

Conclusions: Toxin-positive CDI is more severe, but there were no differences in adjusted CDI-related complication and mortality rates between toxin-positive and NAAT-positive-only CDI that were detected by an algorithm that utilized an initial glutamate dehydrogenase screening test.

Keywords: Clostridioides difficile infection; CDI; diagnostic testing; outcomes.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. D. N. G. is a member of the scientific advisory boards of Merck, Rebiotix, Actelion, DaVolterra, and Summit; is a consultant for Pfizer, MGB Pharma, and Sanofi Pasteur; holds a research grant from Seres Therapeutics; and holds patents and technology for the prevention of Clostridioides difficile infection. G. D. serves on the drug safety monitoring board for a C. difficile treatment study by Seres Therapeutics. M. K. serves on the Board of Directors of the Infectious Disease Consulting Corporation; has received conference travel reimbursement from the Society for Healthcare Epidemiology of America, the Council of State and Territorial Epidemiologists, and the Association for Professionals in Infection Control and Epidemiology; and reports an honorarium and travel reimbursement from Medscape. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Clinical laboratory diagnostic testing algorithm for Clostridioides difficile infection (CDI). The first step of the testing algorithm consisted of a combined glutamate dehydrogenase (GDH) and toxin enzyme immunoassay (EIA). Specimens positive for both GDH and toxin EIA were considered CDI positive and were reported to Emerging Infections Program (EIP) sites. Specimens negative for both GDH and toxin EIA were considered CDI negative and were not reported to EIP sites. Specimens with discordant GDH and toxin results were reflexed to nucleic acid amplification tests (NAATs). Discordant specimens positive by NAAT were considered CDI positive and were reported to EIP sites. Data regarding the discordant GDH/toxin results (ie, whether cases were GDH positive/toxin negative or GDH negative/toxin positive) were available for 83.9% of these cases (see footnote b). Discordant specimens negative by NAAT were considered CDI negative and were not reported to EIP sites. aSince only CDI-positive results were reported to EIP sites, the total number of patients initially tested by GDH and toxin EIA and the total number of patients who tested negative at each step of the algorithm were not available. bA total of 2730 discordant GDH/toxin cases had a positive NAAT result; 2290 (83.9%) had data available regarding the results of the GDH/toxin EIA testing, and 440 (16.1%) did not. Of the 2290 cases with data available, 2278 (99.5%) were GDH positive/toxin negative and 12 (0.5%) were GDH negative/toxin positive. c2718 GDH-positive/toxin-negative/NAAT-positive cases were classified as NAAT positive only for the analysis. Of these, 2278 were confirmed as GDH positive/toxin negative and 440 were assumed to be GDH positive/toxin negative. We made this assumption based on the increased sensitivity of GDH over toxin EIA and the fact that 99.5% of discordant cases with known GDH/toxin testing results were GDH positive/toxin negative. dTwelve cases were GDH negative/toxin positive/NAAT positive; although extremely rare, the negative GDH in these cases might represent a false-negative result. These cases were classified as toxin-positive CDI cases for the analysis.
Figure 2.
Figure 2.
Unadjusted Kaplan—Meier curves of time to death for toxin-positive and nucleic acid amplification test-positive-only Clostridioides difficile infection (CDI) cases. Time to death was followed for up to 90 days following CDI diagnosis for all cases. Abbreviation: NAAT, nucleic acid amplification test.
See this image and copyright information in PMC

Comment in

References

    1. Magill SS, Edwards JR, Bamberg W et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014; 370:1198–1208. - PMC - PubMed
    1. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015; 372:825–34. - PMC - PubMed
    1. Agency for Healthcare Research and Quality. Healthcare cost and utilization project. Clostridium difficile hospitalizations 2010–2014. Available at: hcup-us.ahrq.gov/reports/HCUPCDiffHosp2010-2014Report102616.pdf Accessed 12 June 2018.
    1. Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005; 353:2442–9. - PubMed
    1. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353:2433–41. - PubMed

Publication types

MeSH terms