Invasive candida infections are a major cause of death and disability in U.S. hospitals, preying on critically ill patients who are unable to fight the fungus off. While targeted therapies can help, the real challenge is identifying the infection in a timely manner and distinguishing it from other sepsis pathogens.
The magnetic resonance (T2MR) platform of Lexington, Massachusetts-based T2 Biosystems aims to address this need. It gained FDA clearance in 2014 for its T2Candida Panel, used in conjunction with the T2Dx instrument, by demonstrating it could rapidly detect the Candida species with 91.1 percent sensitivity and 99.4 specificity in a pivotal trial. Two peer-reviewed papers released last week show that the tests are holding up in the real world.
The first was based on the DIRECT2 trial, which compared the diagnostic performance of the T2Candida Panel against conventional blood cultures. The second paper reported on the company’s STAMP study, which asked whether the T2Sepsis Solution (which involves several of its products) could reliably indicate when a Candida infection was cleared. In both studies, the diagnostics significantly outperformed the status quo and hinted at some additional benefits, including lower healthcare costs and smarter use of antifungals.
According to Cornelius Clancy, an associate professor of medicine in the University of Pittsburgh’s Division of Infectious Diseases and a principal investigator in the DIRECT2 trial, T2 Biosystems has injected some much-needed innovation into the field.
“One of the things that’s important about Candida infections… is that if you looked at outcomes 20 years ago and you looked at outcomes now, they’re basically stuck where they were,” Clancy explained in a phone interview. “Even with better drugs, the needle has barely moved on outcomes in these infections and the reason is that the diagnostics have been suboptimal. With molecular diagnostics, we may finally be able to come up with treatment approaches that begin to reduce the mortality from this infection.”
Invasive candidiasis is typically detected through a culture; a blood sample is sent to a laboratory to see if a Candida species will grow. While this is considered the gold standard for detection, it’s a bronze-winning performance at best. Data from autopsy studies suggest the cultures correctly identify an infection in between 20-50 percent of cases. Crucially, the tests also take 2-5 days to deliver results.
A Deep-dive Into Specialty Pharma
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By comparison, the T2Candida Panel detected 89 percent of confirmed infections in the 152-patient DIRECT2 study. Results were delivered on average 4.4 hours after collection.
In other words, the technology did its job.
However, Clancy believes further research is needed to prove that patient outcomes were improved and overall healthcare costs were lowered. Previous studies have shown that early diagnosis and treatment of Candida can significantly reduce the mortality rate, but he noted that the DIRECT2 study was not powered to look at those endpoints.
Beyond individual outcomes, there may also be potential public health benefits. As with bacteria, fungi are increasingly resistant to the key therapies used to tackle them. This has led the scientific community to develop so-called “stewardship” programs that promote best practices for preserving the efficacy of antimicrobials, while still delivering the best possible care.
“There are some early reports coming out that if you incorporate a test like this into antifungal stewardship – so for example, having a program that’s going to systematically look at test results and use negative results to stop antifungal treatment earlier – that you can save costs,” Clancy explained. “But that’s going to have to be prospectively validated.”
A test that rapidly delivers a negative result could cut down on the ‘Hail Mary’ use of antifungals when an infection is suspected, yet the blood culture is still pending. Long-term, this can be a risk factor for antifungal resistance and it undoubtedly increases hospital pharmacy costs.
The T2Sepsis Solution could also fill in some knowledge gaps. In the STAMP study, the test improved physician’s ability to determine when a Candida infection had cleared.
“The problem right now is, we can’t use blood cultures to determine the length of treatment that’s ideal,” Clancy said. “Even if patients clear their blood cultures immediately, it doesn’t mean they’re going to have a better outcome than if it hangs around for a couple days. Therefore, we have to treat everyone the same, we have to give everyone at least two weeks of treatment.”
Reliable information that could indicate how long the treatment was needed could lower costs and antifungal use. A study by Healthcare Cost and Utilization Project (HCUP) and the Agency for Healthcare Research and Quality analyzed billings in 2013 and found that sepsis accounted for nearly $24 billion in annual costs, making it the most expensive condition to treat overall in the U.S.
“So that’s something with molecular diagnostics, in general, that’s quite exciting and, again, future studies are going to have to assess what type of strategy is going to be feasible,” he said.
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