Candida: New Rapid Blood Test Could Cut Mortality

Ricki Lewis, PhD

April 25, 2013

A new, rapid test for Candida infections of the bloodstream may cut mortality from 40% to 11%, according to a report published in the April 24 issue of Science Translational Medicine.

Lori A. Neely, PhD, from T2 Biosystems in Lexington, Massachusetts, and colleagues teamed polymerase chain reaction (PCR) and nanotechnology with T2 magnetic resonance (T2MR) technology to create an assay that identifies 5 common species of Candida fungus in just 3 hours, which is up to 25 times faster than the current gold standard of blood culture.

More than 100,000 cases of candidemia occur in the United States each year, and it is the fourth-leading cause of hospital-acquired infection. Immunocompromised individuals are at particularly high risk.

The infection is difficult to identify in blood culture with morphological examination and biochemical testing because the fungal cells are greatly outnumbered. Two to 5 days are typically required to grow enough cells to detect.

Part of the reason for the 40% mortality rate is time to diagnosis. Each hour of delayed treatment increases mortality of sepsis patients up to 8% or more, according to Eleftherios Mylonakis, MD, from Brown University in Providence, Rhode Island, one of the investigators in the study.

The new test, T2Candida, uses PCR to amplify Candida DNA in blood, which hybridizes to superparamagnetic nanoparticles coated with complementary DNA. The nanoparticles aggregate into "microclusters," which greatly alter the T2MR signal.

The approach effectively dampens "noise" DNA from other sources and detects the fungus at levels as low as 1 colony-forming unit/mL. "Spiked blood samples showed 98% positive agreement and 100% negative agreement between T2MR and blood culture," the researchers write.

The assay also performed well on 21 blinded clinical samples (serial samples taken from 3 patients). Accuracy was similar to conventional culturing, but the new assay worked even in the presence of antifungals.

For now, the new assay is a research tool, but the automated, portable device can be used to detect any molecular, immunoassay, or hemostasis target, the researchers write, by changing the oligonucleotide capture probes that festoon the nanoparticles.

Further investigation is needed to determine how accurately the approach can monitor response to treatment and to test the technique on more samples and at lower titers.

"The probes can differentiate Candida species, which is important due to decreased susceptibility or resistance of some species against some antifungals. Thus, this can guide clinicians to not only quick institution of antifungal therapy but also the right choice of antifungal agent," Jose L. Lopez-Ribot, PharmD, PhD, from the South Texas Center for Emerging Infectious Diseases at the University of Texas at San Antonio, told Medscape Medical News.

Dr. Neely and 10 coauthors are employees of T2 Biosystems, which funded the study. Dr. Lopez-Ribot has disclosed no relevant financial relationships.

Sci Transl Med. 2013;5:182ra54. Abstract

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