Beyond the bugs: why toxin detection is key in two-tiered C. diff tests

We recently added C. diff toxin assay to polymerase chain reaction (PCR) as a two-tier algorithm to investigate whether this approach improves patient outcomes and antibiotic stewardship.

Retrospective chart review.

305-bed acute care urban teaching hospital.

All inpatients admitted who tested positive for C. diff by PCR. Testing was performed by provider order on clinical suspicion of infection. Exclusion criteria were patients with chronic diarrhea, history of IBD, and recent gastric bypass surgery.

On April 1, 2023, the two-tier testing algorithm was implemented for patients who tested positive by PCR. The EMR was reviewed through May 1, 2024, to determine whether toxin-positive patients differed from toxin-negative patients with respect to their demographics, clinical characteristics, outcomes, and initiation of antibiotic treatment.

Of 147 consecutive C. diff PCR-positive patients, 32% tested toxin-positive (n = 57) and 51% toxin-negative (n = 90). Demographics were similar across groups. Toxin-positive patients showed more symptoms of colitis, more bloating, a higher average white blood cell count, and had a higher fatality rate. Antibiotics were more commonly prescribed to toxin-positive patients (98%) than toxin-negative patients (56%) (p < 0.01). Of the 90 patients who were toxin-negative, 44% of those were not treated with antibiotics.

Our study supports previous findings that a two-tier testing strategy effectively identifies active C. diff infection rather than colonization, effectively improving antibiotic stewardship efforts. Some toxin-negative patients also had colitis symptoms and responded to antibiotics, indicating that clinical judgment is still needed in cases with discrepant results.