C. Difficile Near-patient Testing Versus Centralized Laboratory Testing: a Cluster Randomized Trial

Antimicrobial resistance (AMR) has been designated as a major priority by the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and the Public Health Agency of Canada (PHAC). PHAC has identified Clostridium difficile infection (CDI) as a Tier 1 AMR priority pathogen. CDI occurs directly as a consequence of antibiotic use and falls under the clinical syndrome of antibiotic-associated diarrhea (AAD). It is the most common cause of infectious diarrhea among hospitalized patients in developed countries like Canada (Skidmore, 1993). The economic cost of CDI in the United States is estimated at USD 5.4 billion, close to 87% of which occurs in healthcare settings (Desai et al., 2016).

Clinical microbiologists have developed a two-step algorithm in which an EIA or an RDT is first used to screen stools for the presence of glutamate dehydrogenase (GDH) antigen derived from C. difficile. The GDH antigen test is very specific (> 95%) and negatives can be reported right away, only requiring GDH-positive or toxin-positive specimens (by EIA or RDT) to be confirmed by NAAT. In Calgary, the two-step algorithm is performed for a population of close to 1.5 million people at an offsite Diagnostic and Scientific Centre (DSC). The use of a testing centre undermines some of the advantages of the rapid testing methodologies developed in recent years, because of increased transportation and processing time.

A key issue in many settings is that testing falls into a separate budget from the treatment of patients with CDI infections. This has the potential to distort the decision of whether to run a test and, if so, what sort of test. The distortions are of two types. First, the hospital may decide to order more tests than is optimal, since the tests are perceived as "free" from the perspective of decision-makers. At the same time, the diagnostic facility may choose low-cost, slow diagnostics, because the costs associated with delays in test results are borne by the hospital. This is a classic case of silos in health care costs inefficiently distorting policy decisions, with potentially negative results for both patient health and costs.

Many institutions follow the clinical practice guidelines provided by the Infectious Diseases Society of America for the management of C. difficile (Cohen et al., 2010). As part of routine Infection Prevention and Control (IPC) management, patients with acute diarrhea of unknown cause are pre-emptively placed in private rooms with additional contact precautions, which mandate the use of gowns and gloves for healthcare workers. This is also known as patient isolation. Investigation for gastrointestinal pathogens is typically initiated and the duration of patient isolation depends largely on the result of microbiological testing. When severe or complicated CDI is suspected, patients are initiated on empiric treatment as soon as the diagnosis is suspected. Generally, oral metronidazole is used for mild-to-moderate CDI and oral vancomycin for severe CDI. Among hospitalized patients with acute diarrhea, initiation of pre-emptive management for CDI is common.

The intervention of interest is implementing a new RDT to Near Patient Testing (NPT); initial screening for CDI to be performed at the on site hospital rapid response laboratory (RRL) instead of the DSC. Techlab Inc. offers a lateral flow assay (C. DIFF QUIK CHEK COMPLETE® test) that detects both GDH and Toxin simultaneously and further simplifies the testing algorithm. As prescribed in the two-step algorithm, GDH and Toxin negatives will be reported out immediately as negative for CDI, while positive or discrepant results will be confirmed at the DSC using NAAT. The vast majority of requests for CDI testing are negative thus allowing a majority of results to be reported immediately without confirmation at the DSC.