Real-Time Clostridium difficle Testing Reduces Costs, Speeds Diagnosis

Brigid Lucey, PhD, a senior lecturer with the Department of Biological Sciences with the Cork Instituted of Technology in Ireland

Brigid Lucey, PhD

Two separate studies from Anaerobe (February 2018) and the American Journal of Infection (January 2018) indicate rising interest and advancements in real-time testing and notifications for Clostridium difficile (C. diff) detection.

This rising interest may reflect the need for a quick, accurate, sensitive and preferably low-cost, means to detect C. diff infections and alert response teams to the infection's presence. Quick and accurate diagnoses can shorten the time between infection and action, allowing for a quick response from infection control teams, reduction in spread of C. diff infection, reduced costs of treatment and reduced time between identification of infection and initiation of effective therapies for patients.

The study published in Anaerobe, lead by Brigid Lucey, PhD, a senior lecturer with the Department of Biological Sciences with the Cork Institute of Technology in Ireland, focuses on the effectiveness of the EntericBio realtime C. diff Assay (EBCD), a molecular assay which detects toxigenic C. diff in stool samples, in comparison to other testing methods.

As described by Lucey and colleagues, the EBCD does not require nucleic acid extraction or purification and has a short runtime of less than 3 hours for 48 samples (including controls). The benefit of a real-time or rapid-detection testing assay for C. diff can help prevent or control C. diff outbreaks.

Lucey and colleagues argue that traditional C. diff tests, such as toxigenic culture and cytotoxin neutralization (CTN) assays, have been identified as the gold standard methods for clinical diagnosis of infection, but state that the draw-back of CTN assays is their time-consuming nature.

Other C. diff testing options are enzyme immunoassays (EIA), and glutamate dehydrogenase (GHD) testing, but Lucey and colleagues point out that these methods have drawbacks. EIA lacks sensitivity, and GHD lacks corresponding high specificity. Molecular-based assays provide solutions to speed and accuracy issues, but are expensive when compared to alternative methods. Lucey and colleagues tested the use of EBCD in 2 United Kingdom testing centers, and 1 Irish testing center, against the in-use testing methods for C. diff detection in each center.

The EBCD was compared in the 2 United Kingdom centers to the C. diff Quik Chek Complete kit (Techlab), with further testing using the Xpert C. diff PCR assay (Cepheid) and PCR Ribotpyping, and in the Irish center to the DIFF CHEK-60 test (Techlab) followed by C. diff Premier Toxins A&B assay (Meridian Bioscience) testing. The study recorded 939 valid results from the 3 centers.

The collected data on EBCD performance showed that sensitivities of the EBCD were 94.7%, 100% and 97.9%, respectively; specificities were 99.6%, 100% and 100%, respectively; positive predictive values were 94.7%, 100% and 100%, respectively, and negative predictive values were 99.6%, 100% and 99.8%, respectively. Only .08% (n=8) of EBCD tests generated an invalid test result.

Lucey and colleagues reported that the switch in all 3 centers from their standard assay to the ECBD provided cost savings to each center, which adopted the EBCD test post-study to replace their former testing methods. The EBCD cost per test was $5.30, a significant reduction from each center's previous testing costs which ran from between $17.30 to $34.50

When asked by MD Magazine, Lucey stated that she hoped more hospitals and healthcare providers would consider molecular assays like the EBCD which she says have "have become a sensitive, specific, affordable and rapid alternative to the traditional gold standard methods and the cheaper-than-gold standard testing algorithms, both of which tend to be more time-consuming to perform than molecular assays."

Lucey also believes time saved was more significant than costs saved when using the EBCD and that the time saved "may be put to uses that benefit patients, not only those whose C. diff test results are reported more quickly, but also to allow more timely reporting of assays for other pathogens that are also part of the daily workload of the same scientists."

The sentiment that speed is key to control of C. diff is 1 echoed in a major article lead by Christian B. Polen, PharmD, MBA, with pharmacy at St. Joseph Hospital in Lexington, KY, who writes that "implementation of a real-time notification system to alert a pharmacist-led ASP [antimicrobial stewardship programs] of toxigenic C. diff resulted in statistically significant shorter times to order entry and subsequent initiation of effective antimicrobial therapy and contact precautions."

Polen and colleagues performed a single-center, retrospective cohort study at St. Joseph Hospital, a 433-bed tertiary medical center in central Kentucky. The study consisted of 2 arms, with the first pre- and the second post- implementation of a real-time notification system alerting their pharmacist-led ASP team when toxigenic strains of C. diff were detected by DNA amplification or anywhere in the microbiology laboratory.

With the C. diff alert system in place, Polen and colleagues reported reduction of time from C. diff detection to ASP team response, which included patients admitted between April 14, 2016, and January 3, 2017, was reduced to 2:05 hours (p = .001) from 5.75 hours during pre-implementation. There was also, according to Polen and colleagues a statistical reduction in the time to order entry of effective therapy for patients particularly those patients classified with severe C. diff.

The time to treatment reduced from 3 hours in the pre-implementation cohort (n=44) to 0.6 hours (0.2-1.44, n=22) in the post-implementation cohort. Polen and colleagues also note that post-implementation infection-related length of stay was reduced from 10.9 days to 9.8 days (p = .70).

"Numerous studies have demonstrated the importance of early initiation of effective antimicrobial therapy," Polen and colleagues wrote.

Both studies suggest that increasing the speed with which C. diff is diagnosed could be key to patient health. Real-time notification of C. diff presence and accelerated rates of detection through testing speed up the response times of physicians and healthcare facilities, allowing for quicker interventions for patients and the environment. Reducing delays can help stop the spread of C. diff and initiate treatment to patients quickly, which could potentially decrease hospital stays, reduce mortality rates, reduce costs for patients and hospitals, and help patients on their way to recovery.

"Three-centre evaluation of laboratory Clostridium difficile detection algorithms and the EntericBio realtime C. difficile assay" appears in the February 2018 issue of Anaerobe. The "Impact of real-time notification of Clostridium difficile test results and early initiation of effective antimicrobial therapy" was published in the American Journal of Infection Control 3 in January 2018.

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