NEW YORK (360Dx) – Momentum Bioscience has developed an enzyme template generation and amplification (ETGA) technique that could contribute to hospitals' antimicrobial stewardship programs by reducing the time to validate a negative blood culture.
The Cardiff, Wales-based firm said that its ETGA test relies on blood culture growth that takes 12 to 15 hours and then combines phenotypic and molecular analyses to validate within 3 hours that the blood test is negative. Normally, that takes around five days to accomplish, Helen Bennett, Momentum's market development manager, said in an interview.
Reducing the amount of time spent confirming a negative result enables clinicians to act quickly to remove patients from antibiotics, which has "a knock-on effect" for achieving antimicrobial stewardship, Bennett said, adding that the test also has the potential to "significantly reduce" the length of stay in hospitals for patients suspected of sepsis but who turn out to be not infected.
Matthew Dryden, an infectious disease doctor at Hampshire Hospitals Foundation Trust, participated in a study that tested the utility of the test and published the results with colleagues on Friday in the International Journal of Pharmacy Practice.
He said that the test's concept goes against the grain from a clinical diagnostics perspective.
"People have to stop to think about it," he said, "because normally when you're doing a diagnostic test you're looking for a positive result. This test identifies patients that are not bacteremic or fungemic with a high level of specificity, and it appears to be among the most rapid tests available for giving an accurate negative result."
The UK observational study tested 246 patients with suspected sepsis. In 74 percent of cases where the Momentum Bioscience test gave a negative result, there was a positive antimicrobial stewardship outcome, the researchers said. These outcomes included taking patients off antibiotics, switching them to oral from intravenous antibiotics, discharging them from the hospital, and — in some instances — not starting them on antibiotics.
Momentum Bioscience's technology looks for all organisms that could contribute to sepsis, and it can confirm with a predictive value of 99.5 percent when a test result is negative, Bennett said.
Among the key pieces of the test is that it exploits DNA polymerase, an enzyme that repairs DNA and that also helps the growth of bugs that lead to bloodstream infections such as sepsis.
During testing, the system lyses a blood sample releasing the DNA-modifying enzymes that are then incubated along with a synthetic DNA substrate. "In our technology, we've created a DNA template that has a piece missing," Bennett said. "The enzyme wants to repair it and make it double-stranded, so it copies our template, and that's what we detect by PCR. Every DNA polymerase in a bacterial and fungal pathogen makes the same type of copy because we've put that substrate in the mix." If sepsis-causing microorganisms are not present in the sample, the system will not create a PCR target and no amplification will occur.
"We're saying that something exists in the blood culture that will lead to an infection, or nothing exists and the result is negative," but the test is not identifying or seeking out a particular pathogen, Bennett said.
Most tests in the market to manage sepsis are used with blood culture methods that grow pathogens, and they seek to identify the pathogens when results are positive. From there, a physician can decide whether to conduct an antimicrobial susceptibility test that evaluates whether the pathogen will respond to a given therapy, such as an antibiotic.
Physicians sometimes employ commercial tests that use procalcitonin, a biomarker that tells them whether the patient is responding to an antibiotic. These tests, taken together, provide information that help clinicians in the quest to detect sepsis and make treatment decisions, including whether to prescribe antibiotics, Vince Tumminello, director of market access in the US for BioMérieux, a provider of tests for infectious diseases including sepsis, said recently in an interview.
Dryden noted that the new test could be particularly useful for certain groups of patients, including those that present with signs of a possible infection but are already immunosuppressed. "If you can show at an early stage that these patients are not bacteremic, then you can avoid using antibiotics and eliminate the risk of increasing antibiotic resistance," Dryden said.
The test could also prove useful when patients suspected of having contracted sepsis present to an intensive care unit, he noted. "In clinically ill patients, one of the early signs of infection is a small physiological change in an organ parameter, such as renal function, liver function, respiratory requirements, or cardiovascular performance. If they are risk-averse, intensive care units could start antibiotics at that stage," Dryden said, so "having a marker that says the patient is not bacteremic" would alter the decision to proceed with antibiotics.
Some physicians start neonatal patients on broad-spectrum antibiotics for 24 to 48 hours just in case they are infected, Dryden said. If this test could be used on those patients to definitively determine they are not bacteremic, it would be possible to withhold more antibiotics in that group, he noted, adding that "There are a whole variety of patients who would benefit from this early test to avoid unnecessary use of antibiotics."
Bennett said that up to 70,000 newborns per year in the UK, and about 500,000 in the US are at risk for sepsis. Neonates with risk factors of infection in the UK usually receive the antibiotic gentamicin, but all antibiotics are toxic for babies, she said, adding that at 36 hours, the neonates may be given a second course.
In 2015, she and her colleagues did an economic study, with two neonatology units in the NHS system, of full-term babies who were suspected of having early onset sepsis.
"The study showed that by incorporating the ETGA test in diagnosing 600,000 babies, we could eliminate 40,000 doses of harmful antibiotics, and 17,500 patient bed-days per year," Bennett said.
The Momentum Bioscience test has been undergoing clinical trials since 2015.
"We wanted to get it out there and run clinical trials that test its utility," Sumi Thaker, the company's CEO, said in an interview. "We have three trials running and [the Hampshire Hospitals Foundations Trust study] is the first to report data."
Momentum Bioscience is conducting a series of studies with the objective of obtaining CE marking and US Food and Drug Administration clearance to market a commercial in vitro diagnostic test.
The firm is working to automate the test so that labs will find it easier to integrate it into their workflows. It will start a trial in the US in December that employs the automated version, Thaker said.
He noted that the firm anticipates receiving CE marking "toward the end of 2018 or in the beginning of 2019," and FDA clearance sometime in 2019.
The firm has received backing from Longwall Ventures, WrenCapital, and Finance Wales Cyllid Cymru. It is currently participating in a financing round with the objective of raising £2.5 million ($3.2 million), of which it has raised £1.4 million to date, Thaker said.
The firm is developing a new aspect to its test, he said. "The first part of our test rules out sepsis, but we've also recognized that our technology could be used to 'rule in,'" he said.
A slow-growing pathogen might take 20 hours, he said, but with the current test laboratorians are pulling the bottle from the incubator at 15 hours. In a case like this, "We can confirm whether a slow-growing pathogen exists, so we are developing that technology to expand on our current IP," Thaker said.