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Study Vets Abbott Plex-ID Platform as Tool for Broad Fungal ID Directly from Clinical Specimens

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Researchers from the Mayo Clinic have demonstrated that Abbott's Plex-ID broad fungal assay is as good or in some cases better than culture-based methods for identifying fungal infections to the species level directly from respiratory specimens without prior knowledge of the offending organism.

Because the assay is much faster than culture-based methods — offering a turnaround time of hours as opposed to days — it has the potential to be an ideal tool to rapidly diagnose fungal infections and begin antibiotic therapy in immunocompromised patients such as transplant recipients or burn victims.

The results build on similar findings reported last year, but are significant, according to the study's authors, because they are the first data stemming from an evaluation of a Plex-ID system installed in a clinical laboratory — previous studies used specimens gathered at the clinical site but sent to Abbott for analysis.

However, the Mayo researchers also surmised that the Plex-ID platform, which is currently marketed for research use only in the US, may not be practical to use for all patients or specimen types because of its high cost. These concerns, though, may soon be somewhat alleviated as Abbott is currently developing a next-generation version of its system that is more user-friendly, appropriate for clinical diagnostic laboratories, and presumably less expensive.

The Plex-ID system is based on technology that Abbott brought on board as part of its acquisition of Ibis Biosciences in 2009. The platform combines automated sample preparation, broad PCR amplification, and electrospray ionization mass spectrometry of DNA amplicons to identify base composition based on molecular weight — an approach known as PCR/ESI-MS.

Plex-ID can screen and identify bacteria, viruses, fungi, and protozoa by comparing assay results to a library of more than 750,000 entries; perform high-resolution subtyping; identify known virulence markers and antibiotic resistance genes; and identify mixtures of microbes direct from a single sample. The system can also analyze as many as 250 samples per day and can produce results within 8 hours, from sample preparation to identification, according to the company.

Early on, both Ibis and Abbott targeted the system at applied markets such as biodefense, but in the past year the company and its collaborators have published multiple peer-reviewed studies and presented at scientific conferences on the clinical diagnostic potential of Plex-ID.

The latest of these studies, led by the Mayo team, was published online last week in the Journal of Molecular Diagnostics. In it, the researchers compared the analytical performance of the Plex-ID broad fungal assay with that of traditional culture identification using 91 characterized fungal culture isolates and 395 respiratory specimens, resolving discrepant results with sequencing.

"We became interested in [Plex-ID] because it's one of the first platforms that allows us do broad-range detection of fungi without needing to grow them in culture first," Nancy Wengenack, corresponding author on the study and an associate professor of laboratory medicine and pathology at Mayo, told PCR Insider this week.

"That's kind of the holy grail of mycology, is not having to wait for something to grow on a culture plate, but detecting it directly from the specimen," Wengenack added.

She said that the group evaluated the platform first with fungi growing in culture, "just to see how it did on culture isolates — because if it didn't do well there, there was no point in looking at other specimens. Then we looked at respiratory specimens to see how well it would do at direct detection without waiting for growth in culture — broncheoalveolar lavages, sputum, tracheal secretions, things like that."

The assay did perform well on cultured fungi, correctly identifying 87 of 91, or 95.6 percent; and 74 of 91, or 81.3 percent of culture isolates to the genus and species level, respectively.

The researchers noted that Plex-ID correctly identified 100 percent of the organisms that Abbott claims in the assay to the genus level; and 92.2 percent of those organisms to the species level.

"We kind of stretched it and said, 'Sometimes we don't see just those things in patients — sometimes we see other things, and what will [the assay] do when we see those? Will it make a mistake?'" Wengenack said. "We don't want it to tell us it's one thing and have it be another."

Of the 395 respiratory specimens tested directly by Plex-ID, 223, or 56.5 percent, had growth present, and 172, or 43.5 percent, had no growth observed in fungal culture subsequently initiated from the specimen.

Direct analysis of respiratory specimens resulted in 67.6 percent (267 of 395 specimens) and 66.6 percent (263 of 395) agreement with culture results to the genus and species level, respectively. In addition, 16.2 percent of results were discordant with culture, and 16.2 percent were not detected by Plex-ID. The researchers noted that the majority of isolates not detected directly by Plex-ID ultimately grew in low quantities in culture.

Further, in 20.3 percent of respiratory specimens where no growth was observed in culture, Plex-ID identified a fungal species, indicating a potential increase in sensitivity over culture in some instances, the authors reported.

"Things that don't grow in culture … we were able to pick up with Plex-ID," Wengenack said, providing as a particularly relevant example Pneumocystis jirovecii, which commonly causes pneumonia, especially in immunocompromised patients.

The results of the Mayo group's study are similar to those obtained by a group at Vanderbilt University Medical Center and presented in a paper published in JCM last year. As reported by PCR Insider in November, that group found that Plex-ID was able to identify a significantly greater number of fungal agents than culture-based methods (PCR Insider, 11/29/2012).

As noted in the more recent paper, however, the Vanderbilt researchers sent their specimens to Abbott for analysis on Plex-ID, while the Mayo researchers used a Plex-ID installed in their laboratory. "Thus, this study is the first to assess the performance of the Plex-ID system in the hands of a clinical mycology laboratory," they wrote. In addition, the Mayo study "is one of the first evaluations of the Plex-ID broad fungal assays kit ... [in] well-characterized culture isolates and directly from respiratory specimens."

Overall, the researchers lauded the Plex-ID system's potential to provide clinical labs with the ability to perform broad-range, direct identification of fungi without the need to grow the organism in culture first and without the need to have prior knowledge of what the organism might be, as is the case with PCR.

"This is a tremendous advancement in mycology but it comes with a significant cost, with the Plex-ID system priced in excess of $500,000, not including associated equipment and service contract fees," the researchers wrote. They also determined that the cost to analyze a single sample on the Plex-ID system would be about $160.

However, a significant advantage of the platform is that it can be adapted to multiple applications, including identification of bacteria, mycobacteria, parasites, and viruses, without prior knowledge of the offending organism, which may make Plex-ID "a more financially feasible option than it appears at first glance, especially among reference or public health laboratories," the researchers wrote.

Last April, Abbott received CE marking in the European Union to market Plex-ID platform along with three assays: Plex-ID Viral IC Spectrum, Plex-ID BAC Spectrum BC, and Plex-ID Flu (PCR Insider, 4/5/2012).

And in addition to the broad fungal assay, the company has also developed a BAC detection test, and offers a variety of RUO Plex-ID assays including tests for biothreats, Clostridium difficile, food-borne illnesses, methicillin-resistant Staphylococcus aureus, and multi-drug-resistant tuberculosis.

Abbott also said in November that it is planning to discontinue the current version of Plex-ID in favor of a next-generation system that would be more conducive to use in a clinical lab. Presumably this new platform would also be smaller and less expensive. However, a company spokesperson this week told PCR Insider only that the development of the new system is "well underway and expected to launch in the near future."

It remains unclear whether Abbott plans to seek US Food and Drug Administration approval for a newer version of the system.

For their part, the Mayo researchers are eagerly anticipating a next-generation version of the platform.

"We're excited, and kind of anxiously awaiting the re-release of the new platform, and are hoping to be one of the early groups to take a look at it," Wengenack said. The redesign, she added, was "mostly because of mechanical issues, not because of the science behind it or the detection algorithms — it's going to be more user-friendly."

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