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

• Authors: Alice Y. Guh, Centers for Disease Control and Prevention; Kelly M. Hatfield, Centers for Disease Control and Prevention; Lisa G. Winston, University of California San Francisco; Brittany Martin, California Emerging Infections Program; Helen Johnston, Colorado Department of Public Health and Environment; Geoffrey Brousseau, Colorado Department of Public Health and Environment; Monica Farley, Emory University; Lucy Wilson, Maryland Department of Health; Rebecca Perlmutter, Maryland Department of Health; Erin C. Phipps, University of New Mexico; Ghinwa K. Dumyati, University of Rochester; Deborah Nelson, University of Rochester; Trupti Hatwar, University of Rochester; Marion A. Kainer, Tennessee Department of Health; Ashley L. Paulick, Centers for Disease Control and Prevention; Maria Karlsson, Centers for Disease Control and Prevention; Dale N. Gerding, Loyola University Chicago; L. Clifford McDonald, Centers for Disease Control and Prevention
• Journal Title: CLINICAL INFECTIOUS DISEASES
• Volume: Volume 69, Number 10
• Publisher: OXFORD UNIV PRESS INC | 2019-11-15, Pages 1667-1674
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1093/cid/ciz009
• Subjects: Health Sciences, Immunology; Biology, Microbiology; Health Sciences, Health Care Management
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Infectious Diseases; Microbiology; Clostridioides difficile infection; CDI; diagnostic testing; outcomes; POLYMERASE-CHAIN-REACTION; CLINICAL CHARACTERISTICS; MOLECULAR TEST; STRAIN TYPE; DIAGNOSIS; PCR; PREVALENCE; DIARRHEA; OUTCOMES; AMERICA

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.