FDA has recently granted premarket notification (510(k)) clearance for the first blood test for direct detection of five yeast pathogens that cause bloodstream infections: Candida albicans or Candida tropicalis, Candida parapsilosis, and Candida glabrata or Candida krusei.

The T2Candida panel and the T2Dx instrument received clearance for the direct detection of Candida species in human whole blood specimens from patients with symptoms of, or medical conditions predisposing the patient to, invasive fungal infections. The panel test and instrument are the first two products of T2 Biosystems, Lexington, Mass, an in vitro diagnostics company focused on developing innovative products to improve patient health.

T2Candida and T2Dx, for the first time, provide sensitive detection of specific sepsis-causing pathogens directly from a whole blood specimen in approximately 4 hours. All other FDA-cleared detection systems require cultured blood samples for species-specific identification, and take at least 2 to 5 days to provide results.

Yeast bloodstream infections are a type of fungal infection that can lead to severe complications and even death if not treated promptly. These yeast pathogens may cause serious bloodstream infections—sepsis—in people with weakened immune systems, including severely ill patients in intensive care units, patients undergoing cancer treatment, and patients receiving immunosuppressive therapy following an organ transplant.

Sepsis is one of the leading causes of death in the United States and the most expensive hospital-treated condition, with costs to the healthcare system exceeding $20 billion each year, according to the US Department of Health and Human Services.

Mylonakis

Eleftherios Mylonakis, MD

“T2Candida and T2Dx have the potential to quickly change the hospital care paradigm and improve outcomes by offering a new and effective screening option for patients who are at-risk or suspected of having sepsis,” says Eleftherios Mylonakis, MD, PhD, professor of medicine and medical science at Brown University, and chief of the division of infectious diseases at Rhode Island Hospital and the Miriam Hospital. “Compared to current blood-culture based diagnostic methods, T2Candida and T2Dx give us an option that provides specific and dependable results in a matter of hours, not days, allowing us to direct the right therapy to our patients—potentially saving their lives.”

Studies have shown that if Candida can be diagnosed and treated with targeted therapy beginning within 12 hours of the presentation of symptoms, the associated mortality rate can be reduced from approximately 40% to 11%. Additionally, a typical patient with a Candida infection averages 40 days in the hospital, including 9 days in intensive care, resulting in an average cost per hospital stay of more than $130,000 per patient. In a study published in the American Journal of Respiratory and Critical Care Medicine, providing targeted antifungal therapy within 24 hours of the presentation of symptoms decreased the length of hospital stay by approximately 10 days and decreased the average cost of care by approximately $30,000 per patient.

Traditional methods of detecting yeast pathogens in the bloodstream can require up to 6 days, and even more time to identify the specific type of yeast present. The T2Candida panel and T2Dx instrument can identify five common yeast pathogens from a single blood specimen within 3 to 5 hours. Because yeast bloodstream infections are uncommon, and because false positive results are possible with the T2Candida test, FDA advises that physicians should perform blood cultures to confirm T2Candida results.

Gutierrez

Alberto Gutierrez, PhD

“By testing one blood sample for five yeast pathogens—and getting results within a few hours—physicians can initiate appropriate anti-fungal treatment earlier, and potentially reduce patient illness and decrease the risk of dying from these infections,” says Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Health in FDA’s Center for Devices and Radiological Health.

Due to the high mortality rate and cost of Candida infections, many hospitals initiate potentially inappropriate antifungal drugs while waiting for blood culture-based diagnostic results. A negative result from T2Candida may provide timely data, allowing physicians to avoid or suspend unnecessary antifungal treatment. This could result in a further reduction of treatment costs, as well as potentially helping to reduce antimicrobial resistant organisms, which the Centers for Disease Control and Prevention has called “one of our most serious health threats.”

T2Candida and T2Dx are the first diagnostic products powered by T2 Biosystems’s T2MR, an innovative and proprietary magnetic resonance-based diagnostic technology platform that offers a fast, sensitive, and simple alternative to existing diagnostic methodologies. To date, more than 100 peer-reviewed publications have featured T2MR in a variety of studies, including the direct detection and measurement of targets in various sample types, such as whole blood, plasma, serum, saliva, sputum, and urine.

The T2Candida and T2Dx system incorporates technologies that break the yeast cells apart, releasing their DNA. It then makes many copies of the target DNA, and detects the amplified DNA using magnetic resonance technology. If yeast DNA is found, T2Candida will also presumptively determine the species category to which it belongs—information that helps to guide healthcare providers in providing appropriate treatment.

FDA reviewed T2Candida and T2Dx through its de novo classification process, a regulatory pathway for certain novel low- to moderate-risk medical devices.

In their pivotal trial, T2Candida and T2Dx demonstrated a sensitivity of 91.1% and a specificity of 99.4%. The mean time to a positive result for T2Candida was 4.4 hours versus 129 hours for blood culture and species identification, the current gold standard. The mean time for a negative result for T2Candida was 4.2 hours, compared to 120 hours for blood culture.

FDA based its review on a clinical study of 1,500 patients, in which T2Candida correctly categorized nearly 100% of the negative specimens as negative for the presence of yeast. In a separate clinical study of 300 blood samples with specific concentrations of yeast, T2Candida correctly identified the organism in 84% to 96% of the positive specimens.

“FDA’s market authorization of T2Candida and T2Dx mark a significant milestone for our company, but more importantly for the more than 800,000 US physicians across the country in need of faster diagnostic results so they can make timely and informed treatment decisions for their patients,” says John McDonough, president and CEO of T2 Biosystems. “We believe the diagnostic capabilities offered by these products can support both improved clinical outcomes, as well as strong health economic benefits, and we look forward to working closely with the medical community to bring this novel diagnostic test to hospitals, physicians, and patients.”

For more information, visit T2 Biosystems.