Two-Step Testing Helps Predict and Treat Recurrent C difficile Infection


This study explores the effectiveness of toxin testing in predicting Clostridioides difficile infection (CDI) outcomes, revealing that patients with negative toxin results were less likely to experience CDI recurrence within 30 days.

This article was originally published on Contagion Live. It has been lightly edited.

Clostridioides difficile is a bacterium that can cause life-threatening diarrhea and disease in individuals with dysbiosis of the gut microbiota. The CDC estimates there are close to half a million C difficile infections (CDIs) each year in the United States alone.

Risk factors for severe or fatal CDI include age 65 years or older, a current or recent hospital or nursing home stay, a weakened immune system, and/or a previous CDI. Rapid testing and treatment implementation is the best way to increase the odds of survival in these at-risk individuals and the overall population.

Polymerase chain reaction (PCR) testing is highly sensitive for C difficile detection. Additionally, some clinical laboratories have implemented a 2-step testing algorithm, consisting of a PCR test and toxin enzyme immunoassay (EIA) to ensure proper diagnosis.

One study, published in Infection Control & Hospital Epidemiology, sought to determine the risk factors and outcomes of C difficile PCR positive/toxin-positive patients compared to PCR-positive/toxin-negative patients. The study’s primary outcome was the frequency of CDI treatment initiation.

The retrospective case-control study was conducted at a Veterans Affairs hospital. Included patient encounters had a positive C difficile PCR test and either a toxin EIA-positive assay (confirmed cases) or toxin EIA-negative assay (controls). Available encounter stool specimens were cultured for C difficile and restriction endonuclease analysis (REA) strain typing was performed. At 30 days, the investigators assessed CDI recurrence according to clinically relevant exposures and risk factors.

Among 130 C difficile PCR-positive patient encounters, the investigators determined 61.5% (n = 80) were toxin EIA negative and 38.5% (n = 50) were toxin EIA positive. Toxin-positive patents were tested more frequently (96.0%) than the toxin-negative patients.

Multivariable logistic regression modelling revealed that toxin-negative patients were less likely to experience a recurrent CDI episode within 30 days (odds ratio [OR], 0.20, 95% CI, 0.05–0.83). A higher C difficile PCR cycle threshold also predicted a lower risk of CDI recurrence at 30 days (OR, 0.82; 95% CI, 0.68-0.98).

Notably, during the study period, the REA group Y strain accounted for most toxin-negative patient encounters (32.5%; P = .05), while REA group BI strain accounted for most toxin-positive encounters (24.3%; P = .02).

CDI treatment was initiated in 99% of patients according to the 1-step method and in 79% of patients subjected to the 2-step method. The investigators determined that the testing strategy of PCR plus toxin EIA was a helpful predictor of recurrent CDI.


Crone AS, Wright LM, Cheknis A, Johnson S, Pacheco SM, Skinner AM. Characteristics and outcomes of Clostridioides difficile infection after a change in the diagnostic testing algorithm. Infect Control Hosp Epidemiol. Published online July 18, 2023. doi:10.1017/ice.2023.145

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