Despite being the gold standard for diagnosing CDI, toxigenic stool culture is a time-intensive test (e.g., need for special growth medium and follow-up cytotoxic assay, 1-2 day time requirement). Consequently, studies have evaluated test characteristics for more rapid modalities such as two-step assays and toxin NAAT PCR.

A study conducted at two US hospitals within an academic medical center in 2004¹ evaluated the two-step assay, which assesses samples for the presence of C. difficile by enzyme immunoassay (EIA) and if positive,
progresses to cytotoxicity assay. 266 fecal specimens from hospitalized patients with suspected CDI were sent to the study center and tested via the two-step assay approach. Negative EIA alone had high sensitivity (96%, 95% CI ≥ 79%) and negative predictive value (99.5%, 95% CI ≥ 97.5%) for CDI. These findings support the two-step assay approach and suggest that cytotoxicity assay may not be necessary in EIA-negative samples.

A 2007 observational study done across three hospitals within an academic medical center evaluated the test performance characteristics of toxin NAAT PCR compared to anaerobic culture as a reference gold standard among 618 unformed stool samples.² Compared to culture, toxin NAAT PCR had a sensitivity of 94% and specificity of 97%. Caveats include small number of positive CDI cases.

Given the diagnostic effectiveness of both the two-step glutamate dehydrogenase (GDH) EIA/cytotoxic assay and the toxin NAAT PCR, IDSA guidelines support both modalities (weak recommendation, low quality of evidence) as options for testing patients for whom there is clinical suspicion of CDI.³

This question was addressed in a 2013 single-site study that evaluated 1770 patients admitted to a 20-bed ICU to determine whether being admitted to a room previously occupied by a patient with a CDI
conferred a higher risk of developing CDI for the new occupant.⁴ Acquisition of CDI was measured throughout the duration of patients’ ICU stay and in the 30 days after patients transferred out of the ICU. Those diagnosed with CDI before their ICU stay were excluded from the analysis of new CDI acquisition but were included as potential sources of room exposure. CDI was diagnosed by ELISA for C. difficile toxins.

After controlling for factors such as antibiotic and proton pump inhibitor use, age, and illness severity, admission to a room whose prior occupant had CDI was associated with greater CDI incidence (HR 2.35, 95% CI 1.21-4.54; P = .01). Of note, the study did not control for other medications implicated in CDI risk (e.g., histamine blockers, antimotility agents). Nonetheless, study findings are consistent with IDSA recommendations to use isolation rooms or wards for patients with CDI to limit transmission (strong recommendation, moderate quality of evidence).⁵

Soap and water hand washing is the preferred modality of hand hygiene for eliminating C. difficile.

Because C. difficile endospores can be resistant to elimination with routine hospital antiseptics, this question was addressed in a study of 10 healthy volunteers in Quebec in which modalities of hand hygiene were tested to evaluate their effectiveness for eliminating spores.⁶ Six approaches were tested: warm water/plain soap, cold water/plain soap, warm water/antibacterial soap, antiseptic hand wipes, alcohol-based hand rub, and no handwashing. Contamination was achieved by a
“whole-hand protocol,” in which 20 mL of a C. difficile inoculum was poured into a glove and participants’ hands were placed in the glove, and a “surface contamination protocol” in which participants placed both palms on a ceramic tile that was contaminated with C. difficile. Participants were not trained in any particular hand washing technique. The outcome of interest was the mean reduction in C. difficile colony forming units (CFUs).