SAN DIEGO – The T2 magnetic resonance assay for rapid diagnosis or rule-out of invasive candidiasis has the potential to significantly change the management and outcome of this common, deadly, and expensive disease, Dr. Peter G. Pappas asserted at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

This novel diagnostic instrument addresses a longstanding major unmet need in the field of infectious diseases: namely, the necessity for a substantially faster and more accurate test for invasive candidiasis than the decades-old current standard, which is automated blood cultures.

Blood cultures are notoriously insensitive. Indeed, they are negative in roughly 50% of patients with invasive candidiasis, mainly those with deep-seated, noncandidemic invasive candidiasis. And blood cultures are far too slow, taking 2-5 days to finalize results, explained Dr. Pappas, professor of medicine at the University of Alabama, Birmingham. “Management of invasive candidiasis involves time-critical decision making. The earlier we can approach the patient with specific therapy, the better the outcomes. That actually hasn’t been shown prospectively, but it’s a reasonable assumption based upon the available retrospective studies. We would like to be able to initiate effective treatment within 12-24 hours; that’s seldom possible with blood cultures,” he continued.

Dr. Pappas was principal investigator in the direct T2 pivotal clinical trial which led to Food and Drug Administration approval of the T2 magnetic resonance assay, known as the T2Candida platform. In this 1,801-patient multicenter study, the assay provided results in a mean of just over 4 hours with 91.4% sensitivity, 99.4% specificity, and a negative predictive value of 99.2%. In contrast, blood cultures, which were obtained in all participants, required an average of more than 120 hours to provide results (Clin Infect Dis. 2015 Mar 15;60[6]:892-9. doi: 10.1093/cid/ciu959).

At ICAAC 2015, the clinical trial was named one of the top 10 papers of the year in mycology.

Invasive candidiasis is a huge problem that’s seen little in the way of progress over the past 2 decades. Candida infections account for 6% of all hospital-acquired infections in the United States. More than 400,000 cases of invasive candidiasis occur annually worldwide. Attributable mortality rates of up to 49% have been reported. The disease is an important cause of prolonged hospitalization, with episodes adding an average of about $40,000 to the cost of a hospital stay.

The T2Candida test not only enables physicians to get effective antifungal agents started quickly, but a negative result will allow a drastic cutback in the now-routine use of empiric antifungal therapy prescribed during the lengthy wait for blood culture results. This will reduce needless exposure to drug side effects among uninfected patients, discourage the rise of resistant Candida strains, and substantially reduce health care costs.

Extrapolating from this trial’s data, and from other studies, Dr. Pappas said “the sweet spot” for the assay, where it has an impressively high 75%-85% positive predictive value, occurs when it is applied to patients with a pretest probability of invasive candidiasis in the 3%-10% range based upon well-known high-risk factors, including current cancer, neutropenia, organ or stem cell transplantation, having a central venous catheter, or being on steroid therapy.

The new assay bypasses blood cultures entirely, instead employing molecular diagnostics to directly analyze a whole blood sample. It can identify C. albicans and four other clinically relevant Candida species which collectively account for the vast majority of cases of invasive candidiasis. One of the reasons panelists at ICAAC 2015 named the T2Candida pivotal trial to their top-10 list of major papers in mycology is that the T2 magnetic resonance technology is a platform capable of also being applied to the diagnosis of other pathogens whose prompt diagnosis is critical.

Another advantage of the T2Candida platform is that the results are unaffected by antifungal therapy. In contrast, blood cultures become unreliable if a patient has empiric antifungal therapy onboard. In a separate presentation at ICAAC 2015, Dr. Pappas and coworkers presented interim results from an ongoing study that capitalizes on this advantage of the new technology.

To date, the study has enrolled 23 patients with culture-proven candidemia, all of whom underwent daily testing via both blood cultures and T2Candida during their first 7 days on antifungal therapy. Blood cultures remained positive for only two patients on-treatment, whereas T2Candida remained positive for nine patients on all 7 days and also detected one new case of intra-abdominal candidiasis missed by blood cultures.

Thus, the T2Candida platform may be an effective method not only for diagnosis of invasive candidiasis, Dr. Pappas observed, but for monitoring the response to therapy in the form of antifungal agents and/or removal of an offending contaminated catheter.

Dr. Pappas reported receiving research grants from and serving as an advisor to T2 Biosystems, which markets the assay. He has also received research support from Astellas, Gilead, and Merck.

bjancin@frontlinemedcom.com

New assay may be a game changer in invasive candidiasis