NEW YORK (GenomeWeb) – A molecular diagnostics panel designed to detect six common bacterial pathogens that infect the gastrointestinal system has been shown in a large evaluation at seven centers in the US and Canada to be more sensitive than bacterial culture or enzyme immunoassay, and equivalently specific.
A prospective and retrospective study, published online this month in the Journal of Clinical Microbiology, evaluated the Enteric Bacterial Panel, or EBP, a PCR-based assay from Becton Dickinson that runs on the firm's BD Max system.
Samples from 4,242 patients were tested at clinical labs in Cleveland; Cincinnati; Milwaukee; Boston; Dallas; Temple, Texas; and Calgary, Alberta. The study also included previously characterized, archived positive samples, as well as samples provided by additional collection sites in the US, Canada, and Mexico. It further compared preserved and unpreserved specimens.
The results of the JCM study were presented in preliminary form at conferences last May, but the new publication will now be helpful for BD, Nikos Pavlidis, the worldwide market segment director for molecular at BD Diagnostics told GenomeWeb in an interview.
"Many labs and clinicians want to understand how a new technology will change and impact they way they do things today, and the way they manage patients," he said. Test performance can also guide decision making, and purchasing, so studies help in "communicating the clinical performance of our product," Pavlidis said.
"A paper like this one, which has quite a good number of samples and is a very comprehensive study, allows labs to understand how this new technology will impact the change from the current tests of record to a new test of record that uses a different technology."
This may be especially useful in communicating to potential customers the benefits of molecular panels, particularly for gastrointestinal symptoms. "The field of enteric pathogens is a new and developing one in the world of molecular diagnostics — it's next in the wave of conversion of the microbiology lab from traditional methodologies like culture or microscopy," Pavlidis said.
One reason for this might be developments in sample prep and PCR technology that tackled previous problems with PCR inhibitors in stool samples. However, now the development of PCR-based enteric panels must match the needs of customers, and commercially available panels seem to be taking different approaches toward this.
BD is taking a tack of making smaller panels to allow labs and clinicians more control over test utilization, Pavlidis explained. This addresses the idea that "most labs today are trying to improve test utilization and avoid overuse of testing," he said.
"We have taken a different approach in the way we design our enteric solutions; we have a focused approach that allows labs and clinicians to improve test utilization," he added.
Test overuse can increase cost, Pavlidis noted. Extensive panels may also have unlikely targets that could yield false positive results, or report positives in cases where a patient is an incidental carrier of a pathogen. This can ultimately provide clinicians with information that might not be relevant to treatment. "It might even be confusing their decision making," Pavlidis said.
Instead of one broad enteric panel, BD now offers its bacterial panel, and will follow that with two additional enteric panels for parasites and viruses. He added that this will allow clinicians and labs to choose a test based on symptoms and risks.
"If you view today how tests are being requested, and also if you review the guidelines … they're actually guiding clinicians to make decisions for which diagnostic test they're using based on all of these things — the risk, the patient history — and when we look today at the way enteric testing is being ordered, it's very clear that they are requesting specific testing, more like the format of the panels that we designed," said Pavlidis.
Study results, future menu
The authors of the JCM study noted that diarrheal disease is the second leading cause of mortality worldwide for children under the age of five, killing around 760,000 each year. Acute gastroenteritis, which can be caused by bacteria, viruses, or parasites, can be difficult to distinguish in the clinic, but knowing the cause is important for treatment and outbreak management.
The study compared BD Max EBP to diagnostic culture for Salmonella spp, Shigella spp, Campylobacter coli and C. jejuni, and EIA for Shiga toxins using soft or diarrheal stool specimens from pediatric and adult patients.
Clinical labs at each site in the study ran the EBP panel on the BD Max system, which, according to the study, can process 24 samples per batch in about three hours with less than two minutes of hands-on time per sample.
Discrepant samples were tested by BD Diagnostics using an alternate PCR method, and, since no true reference method was available, the authors calculated both a positive and a negative "percent agreement" between EBP and the gold standard for each pathogen for prospective, retrospective, preserved, and unpreserved samples.
Overall, the positive agreement of EBP compared to culture or alternate PCR was greater than 97 percent for all targets, and the EBP panel detected an additional 59 cases that the gold standard missed.
The methods also had greater than 99 percent agreement in the samples they called negative, after discrepant samples were resolved.
Twelve samples were positive by gold-standard testing but not EBP, and six of these were also negative with alternate PCR. The authors attributed this to limiting dilution of organism, which may have been otherwise detectable by culture due to broth enrichment in some protocols. They attributed 48 apparent false positive EBP results to enhanced sensitivity for low copy number targets as well as the presence of non-viable organisms that could not grow in culture.
Highlighting the drawbacks of gold-standard culture methods — which are notoriously slow and require technical skill and expertise — the authors noted that nucleic acid amplification methods are beneficial both to diagnosis and to epidemiology. They also pointed out that published clinical evaluations of other commercially available panels have shown similar results, so user preferences should ultimately determine assay selection.
However, "the BD Max EBP assay focuses only on the most prevalent bacterial enteric pathogens, might be characterized as having medium throughput, and requires almost no previous technical expertise in molecular diagnostics," they wrote.
Two of the authors on the study are employees of BD. Two others have received honoraria, according to the acknowledgements. This was not for this study specifically, but was probably associated with communication activities for other BD Max panels or other products, Pavlidis said
The study was part of a clinical evaluation of BD Max EBP, however, and "as in any clinical evaluation, the organization covers at least the part of the cost the reagents and instrumentation," he said.
The firm remains on target to launch its other enteric panels in the near future, Pavlidis affirmed. The enteric parasite panel has debuted in Europe, and has been submitted to the US Food and Drug Administration. It is expected to launch in the US in the third quarter of this year. An extended enteric bacterial panel and separate enteric viral panel are both set to launch in the EU in late 2015 or early 2016.
In addition to smaller, focused panels, the BD Max system is unique in the market because it integrates all the steps of molecular testing within a single platform, Pavlidis said, including extraction, sample transfer, amplification, detection, and results reporting.
"We believe that's a strong differentiator of our BD Max platform, together with the additional menu that we offer beyond the enteric panels," he said, adding that the system also has the ability to automate lab developed tests "with a very similar process as the IVD tests that we have available," as previously reported by GenomeWeb.
"The ability to run laboratory developed tests on the BD Max platform makes it a much more versatile solution, and is actually helping labs … to streamline testing and reduce the number of platforms and processes that run within the lab."
The firm will continue developing the menu for the platform in its areas of expertise, Pavlidis said, which include healthcare-acquired and enteric infections, as well as sexually transmitted and other reproductive tract infections.