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Study Shows High Sensitivity, Specificity for Abacus Diagnostica C. Diff Test

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A new automated molecular diagnostic assay to detect toxigenic Clostridium difficile directly from stool samples was found to have comparable sensitivity and specificity to both the gold standard of culture-based testing and reference testing with a competing assay, Cepheid's GeneXpert C. difficile, according to recently published research.

The test — called GenomEra C. difficile from Finnish company Abacus Diagnostica — may also provide cost and ease-of-use benefits over competing molecular diagnostic assays due to the simplicity of its chip design.

In addition, Abacus is currently developing an even more streamlined version of the assay that it hopes to begin selling to European customers by the end of this month, and anticipates starting clinical evaluation of the test in the US near the end of this year, Mari Gylling, director of marketing and sales at Abacus, told PCR Insider.

The C. difficile assay received CE marking in November, joining the firm's commercially available GenomEra assays for detecting and differentiating Staphylococcus aureus and methicillin-resistant S. aureus from nasal swabs and blood culture (PCR Insider, 11/29/2013).

All of Abacus' tests run on the GenomEra CDX system, a self-contained, fully integrated and automated testing platform designed for routine clinical use. The system requires little to no sample preparation and performs rapid PCR amplification and end-point detection using homogenous time-resolved fluorescence chelates as labels.

According to Gylling, GenomEra C. difficile it is the "first PCR assay that uses feces as sample material with so few sample preparation steps and yet with such good results and low inhibition rate" — characteristics that are due at least in part to the time-resolved fluorescence detection scheme, which essentially eliminates autofluorescence, a common problem when conducting PCR assays on stool samples.

Abacus was selling the GenomEra CDX system prior to the C. diff test, but since that assay launched late last year, the company has nearly doubled the number of installed systems, Gylling said, although she didn't provide exact figures.

The company had previously presented data from clinical evaluations of the assay at various scientific conferences, including the European Society of Clinical Microbiology and Infectious Diseases annual congress in April. However, a study published late last month in the Journal of Clinical Microbiology is the first peer-reviewed paper on the assay to be published.

In the study, clinical researchers from Vassa Central Hospital and the National Institute for Health and Welfare, both in Finland, evaluated the performance of GenomEra C. difficile using 310 diarrheal stool specimens and a collection of 33 known clostridia and non-clostridia isolates.

Specimens were collected between August and September 2012, and were tested by toxigenic culture immediately or refrigerated and tested within 24 hours of receipt. Aliquots of each sample were frozen for later testing with GenomEra C. difficile.

In the case of discrepant results from toxigenic culture and the GenomEra test, specimens were tested with Cepheid's GeneXpert C. difficile assay.

Of the 310 stool specimens examined, 80, or 25.8 percent, were positive for the toxin B gene, tcdB, using the GenomEra test. Meantime, culture-based methods isolated toxin-producing C. difficile from 77, or 25.2 percent, of specimens. Two of the three GenomEra-positive but culture-negative samples were confirmed as tcdB-positive by the Cepheid assay, while one was positive only with the GenomEra test. In addition, one specimen was toxin-positive by culture, and initially yielded an inconclusive result using GenomEra, then yielded a negative result in retesting.

Overall, the results indicated that GenomEra C. difficile had a sensitivity of 98.8 percent and a specificity of 99.6 percent when performed directly on fecal specimens. In addition, the test yielded no false positives or negatives when used on the culture isolate collection, correctly differentiating between a number of different toxigenic or non-toxic Clostridium and non-Clostridium species.

The researchers underscored the simplicity of GenomEra testing, noting that the test produced results in less than an hour with only five minutes of hands-on time. This is a huge improvement over culture-based methods, and comparable to that of Cepheid's test. However, Gylling noted that the Abacus test may provide some additional advantages over the GeneXpert assay.

"The amount of waste due to assay runs is very low, and permanently sealed chips makes the waste handling very easy and safe," she said. "Among tighter rules in laboratory practices, this is highly appreciated." In addition, she noted, "the closed system with sealed chips eliminates the risk of contamination problems in the laboratory and spares the user from cleaning activities." Finally, she added, the assay features "user-friendly reagents [that] do not contain any irritating components."

In terms of cost benefit, the "test chip design is simpler than Cepheid’s cartridge design," which may make GenomEra's cartridges cheaper in the long run, Gylling said, although she declined to quantify this potential cost differential or disclose a price range for the GenomEra CDX system.

And, "as test production volumes are rapidly increasing and bigger batches are produced, we are able to compete even better with the prices [of] other MDX platforms," she added.

The authors of the JCM paper did not provide a cost analysis, but wrote that "laboratories of any size can easily adopt the GenomEra CDX instrument," and "the capacity of the assay is adequate for laboratories performing up to approximately 8,000 to 11,000 C. difficile analyses per year," with 32 sample analyses able to be performed in one eight-hour workday.

"In laboratories with lower numbers of C. difficile samples per year the capacity of the instrument may be used to test additional microbiological targets in order to take full advantage" of the platform, they added.

Indeed, Abacus is planning to add new targets and tests to its portfolio. Besides the commercially available C. diff, MRSA, and SA tests, the company is working on Chlamydia trachomatis, vancomycin-resistant enterococci, and other pathogen-specific markers, Gylling said. "As seen in several market studies and customer feedbacks, HIV, tuberculosis, and norovirus tests are moving fast towards small, easy-to-use molecular diagnostic systems," she added. "The benefits of our system would fit very well to these tests and are naturally among our high research interests."

None of Abacus' tests are available yet in the US. Last August, after winning a key pair of US patents covering its technologies, Abacus told PCR Insider that it planned to seek regulatory approval in the US this year for its MRSA and SA assays, as well as the C. difficile test.

Gylling did not provide an update on the former tests, but noted that the company is set to release an even easier-to-use version of the C. diff test in Europe this month, and plans to begin clinical testing of that assay in the US by the end of this year.

"The increased interest and growth in Eastern Europe, Middle East, Asia, and emerging markets has been [a] high priority among our commercialization efforts and activities during [the] first half of 2013," she said. "However, we still anticipate starting clinical evaluations in [the US] towards [the] end of this year with the new C. difficile version.

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