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Finland's Abacus Diagnostica Looks to Submit MRSA Blood Culture, C. Diff Tests to FDA Next Year

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Finnish molecular diagnostics firm Abacus Diagnostica, fresh off winning a pair of key US patents covering its DNA testing technologies, plans to seek regulatory approval in the US next year for tests to detect Staphylococcus aureus and methicillin-resistant S. aureus in blood culture, and Clostridium difficile from stool samples, according to a company official.

The assays, which run on the company's GenomeEra CDX PCR system, would be the first two slated for commercialization in the US. In Europe, Abacus already offers MRSA/S. aureus tests using various sample types, and is planning to expand its test menu to include assays for C. difficile and two Streptococcus species by the end of this year.

Founded in 2004 as a spinout of the department of biotechnology at the University of Turku, Abacus has developed the GenomeEra CDX system as a platform technology to run a variety of clinical molecular diagnostic tests.

The integrated, sample-to-answer system features proprietary assay chip, thermal cycling, and detection technologies.

The GenomeEra CDX test chips use preloaded dry-reagent chemistry and fluidic channels to eliminate the need for user master mix preparation and reduce the risk of contamination. A sample is added to an inlet on the chip that is subsequently automatically heat sealed. The benchtop analysis instrument accepts holders that can carry four test chips each carrying distinct barcodes that are automatically registered.

Meantime, GenomeEra CDX's multi-block thermal cycler design contains multiple individually controlled thermal blocks that are each adjusted to a distinct temperature in the PCR process. The instrument automatically moves the test chips from one block to another before being moved into the readout phase.

The platform's detection scheme combines proprietary fluorescent lanthanide reporters with a homogenous, time-resolved fluorescence detection scheme. More specifically, the test chips are excited with ultraviolet light, which causes the lanthanide reporters to exhibit prolonged fluorescence, as opposed to the relatively short fluorescence lifetime of autofluorescence generated by various sample matrices.

"By applying a short delay between the sample excitation pulse and the fluorescence counting, the autofluorescence effect is eliminated, which has a significant impact on test sensitivity," according to the company's website.

The upshot is a DNA testing system that requires minimal user intervention and can provide a test result in about an hour, according to the company.

Many companies and academic groups are currently developing similar integrated testing platforms using a combination of different technologies. However, Abacus expects that its system has advantages over competing platforms in ease of use, speed, and accuracy, Mari Gylling, marketing and sales director at the company, told PCR Insider in an e-mail.

Gylling said that the company has patent applications and awarded patents covering its "all-in-one PCR assay chemistry," which requires "no handling of PCR reagents whatsoever;" for its "enhanced competitive probe technology," which provides sensitive detection of low-copy targets; and its time-resolved lanthanide labels.

Abacus also has IP in hand covering its "robust two-step endpoint detection technology," which provides "reliability of result interpretation;" and its pre-heated block thermal cycling technology, test chips, and sample prep method, Gylling said.

Indeed, last week Abacus was awarded US Patent No. 8,247,171, "Method for detection of presence of target polynucleotide in samples," which describes the homogenous time-resolved fluorescence detection method (PCR Insider, 8/21/2012). And in July the company won US Patent No. 7,972,838, "Method for stabilizing assay reagents, reagent container with stabilized assay reagents, and use thereof," describing its test chips (PCR Insider, 7/13/2012).

Several publications over the last few years have vetted the various technological components of Abacus's platform, but one of the first clinical studies using the platform was published earlier this year.

In a study published in May in the European Journal of Microbiology and Infectious Diseases, researchers from Finland's Vaasa Central Hospital evaluated the GenomeEra CDX MRSA/S. aureus blood culture test.

In the study, the scientists used Abacus's test to analyze 316 BacT/Alert and 433 BacTec blood culture bottles from BioMérieux and Becton-Dickinson, respectively, for the presence of methicillin-resistant S. aureus (MSSA), MRSA, and methicillin-resistant coagulase-negative staphylococci (MRCoNS).

The GenomeEra CDX test demonstrated 99.4 percent sensitivity for MSSA; 100 percent sensitivity for MRSA; and 99.3 percent sensitivity for MRCoNS. The test yielded one false positive MRSA result for a specificity of 99.8 percent.

The researchers noted that the test was able to detect viable cells in blood culture down to a level of 4 x 104 colony-forming units/milliliter; that it provided results within one hour after microbial growth detection; and that the "two-step, time-resolved fluorometric measurement method showed no interference from blood, charcoal, or culture media."

The paper's authors concluded that the GenomeEra CDX test "lacks all sample purification steps and [also] allows reliable and simplified pathogen detection in clinical microbiology laboratory settings without specialized molecular microbiology competence."

Abacus currently sells the CE Marked GenomeEra CDX platform in 13 European countries as well as the United Arab Emirates and Israel. The company began selling the system in the first quarter of 2011 and has since placed 34 units that are "either in routine or evaluation use," Gylling said.

The system's test menu in these countries currently comprises assays for MRSA/S. aureus from nasal and multi-swabs, culture plates, and blood culture tubes. According to Gylling, the company's CE Marked test pipeline includes assays for C. difficile from stool, slated to be available by the end of October; and S. pneumoniae and S. agalactiae (Strep B), both expected to be ready by the end of this year.

In 2013 Abacus plans to pursue CE Marking for "other critical pathogen-specific molecular diagnostic tests," Gylling said. The company also intends to file a submission with the US Food and Drug Administration sometime next year for both MRSA/S. aureus in blood culture and C. difficile in stool samples, she added.