A Mayo Clinic research group that previously evaluated Abbott's PCR-electrospray ionization mass spectrometry platform to broadly identify fungal infections has now published research demonstrating the system's ability to identify Mycobacterium species and M. tuberculosis complex drug resistance determinants.
In the study published this month in the Journal of Clinical Microbiology, the group, led by Nancy Wengenack, an associate professor of laboratory medicine and pathology at Mayo, used Abbott's Plex-ID platform to correctly identify all M. tuberculosis complex (MTBC) isolates and more than 97 percent and 95 percent of non-tuberculosis mycobacterial isolates from characterized agar and broth cultures, respectively, to the species level.
In addition, the researchers demonstrated that Plex-ID had a high level of sensitivity and specificity for detecting resistance determinants for four common TB therapeutics compared to existing culture-based methods.
"This is basically a first look to prove that this technology and the calling algorithm, in terms of identifying these organisms, is working correctly," Wengenack told PCR Insider this week. "Obviously if it doesn't work well from culture, you might as well not even look at direct specimen. But it does work well from culture, and positive broth culture, so the next step would be to look at it in specimens like patient sputum … to see how well it identifies these organisms."
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, according to the company. The system can also analyze as many as 250 samples per day and can produce results within 8 hours, from sample preparation to identification.
In March, PCR Insider reported on the publication of a study from Wengenack's group that showed that Plex-ID is at least as good as culture-based methods for identifying fungal infections to the species level directly from respiratory specimens without prior knowledge of the offending organism (PCR Insider 3/28/2013).
The more recent paper, Wengenack said, "is kind of a continuation of the [fungi] studies we've already done with Plex-ID. Now we've looked at Mycobacteria — M. tuberculosis but also the non-TB Mycobacteria, which we actually see more often than TB in patients in the US."
The crucial advantage of Plex-ID, she said, is its potential to directly identify these organisms from nearly any sample type without going through the usual culture growth steps that are so common in microbiology laboratories. "It seems to be something we can use directly without having to wait for growth in culture," Wengenack said. "That sets it apart from other tests out there right now."
Cepheid's Xpert MTB/RIF, which has been on the market for some time in high-burden developing countries and which received 510(k) clearance in late July (PCR Insider 8/1/2013), is one of a very few platforms that can test for Mycobacteria directly from patient specimens. "But that's kind of a limited snapshot, just looking for TB, and we want to look for some of the other non-TB Mycobacteria, as well," Wengenack said.
In the JCM paper, Wengenack and colleagues compared the performance of the Plex-ID MDR-TB assay to identification using nucleic acid hybridization probes and 16S rDNA gene sequencing for 68 MTBC and 97 non-tuberculous mycobacterial isolates grown on agar, and 107 cultures grown in Becton Dickinson Bactec MGIT broth.
The Abbott system correctly identified all MTBC isolates and 97.9 percent and 95.8 percent of the NTM isolates from characterized agar cultures and MGIT broth cultures to the species level, respectively.
The Mayo researchers also compared MTBC resistance profiles from the MDR-TB assay to the agar method and found that the comparative sensitivities and specificities of Plex-ID for the detection of drug resistance were 100 percent and 92.3 percent for rifampin; 100 percent and 93.8 percent for isoniazid; 91.6 percent and 94.4 percent for ethambutol; and 100 percent and 100 percent for fluoroquinolones, respectively.
Both Mayo studies — as well as a number of other studies from independent research groups — demonstrate that Plex-ID has great potential as a clinical tool for diagnosing a broad range of bacterial, viral, and fungal specimens without prior knowledge of the infection. However, the platform may still be at least a year away from true clinical implementation.
The system is currently marketed for research use only in the US, and Wengenack noted that its lack of user friendliness and high cost — currently in the vicinity of $500,000 — still preclude broad adoption of the platform.
Abbott is supposedly addressing these issues with the development of a next-generation version of the platform that will be more user-friendly, appropriate for clinical diagnostic laboratories, and presumably less expensive.
A company spokesperson told PCR Insider in March that development of the new system was "well underway and expected to launch in the near future." However, the company did not respond this week to a request for an update on the development timeline.
As it nears market, the Mayo group hopes to be one of the earliest beta testers.
"They've kind of pulled it back from the market and are re-engineering it, because they've had some problems with some of their lines plugging and just some mechanical issues," Wengenack said. "They want to make it more user-friendly for the laboratory. The last I heard was late 2014. We're excited about getting a look at the new instrument once it comes out, because the old one does a good job of identifying all these organisms."
Wengenack said that her group will "look at Mycobacteria directly from sputum and other specimens as soon as we can get our hands on a new instrument."