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With New Instrument and Assay Claims, BioMérieux Takes on Antibiotic Stewardship11 May, 2017
With a recently approved blood culture system, new indications for its procalcitonin (PCT) diagnostic assay, and an arsenal of molecular testing tools, bioMérieux is aiming to become a leader in the increasingly competitive field of antibiotic stewardship.
by Madeleine Johnson
NEW YORK (360Dx) – With a recently approved blood culture system, new indications for its procalcitonin (PCT) diagnostic assay, and an arsenal of molecular testing tools, bioMérieux is aiming to become a leader in the increasingly competitive field of antibiotic stewardship. Although stewardship has always been "in the DNA" of microbiology-oriented bioMérieux according to Stefan Willemsen, president and CEO of the US division, bioMérieux Inc, it is also increasingly on the radar of hospitals and physicians. This is particularly true given new guidelines from the US Centers for Disease Control and Prevention and The Joint Commission, and awareness campaigns such as the World Health Organization's list of superbugs. Reducing inappropriate use of antibiotics in hospitals through antimicrobial stewardship is postulated to help slow the development of resistant bacterial strains.
bioMérieux plans to highlight to its customers that rapid identification of pathogens enabled by its portfolio of instruments and tests, as well as certain antibiotic decision making enabled by its new PCT claims for sepsis and lower respiratory tract infections, will promote good stewardship and potentially save lives.
At the forefront of the firm's stewardship push is its BacT/ALERT Virtuo blood culture platform, which was cleared by the US Food and Drug Administration last month.
Willemsen said that while it is too early to report any uptake trends in the US, the system has been available in Europe for a while and customers there have appreciated that it is automated and "load-and-go," allowing cultures to be set up and run 24 hours a day. Non-automated systems, on the other hand, are typically more challenging to run in nighttime hours, when highly trained staff is more likely to be unavailable.
The new Virtuo system has also been designed to make it possible to remove individual culture bottles from the run at any time.
"That opens up possibilities to look at protocols in the hospital, together with physicians, pharmacists, [and] lab directors, to improve patient care and improve protocols to ensure that we have faster determination of bacterial infection," Willemsen said. "It generally takes less time forBacT/ALERT Virtuo, from the point-of-sample collection to colony growth, to provide actionable results, [and] this adds to the efficacy of molecular and mass spec platforms. It varies, but [molecular and mass spec] platforms often can be run with less culture growth — which means more time saved," he said.
And, if a molecular test happens to be a syndromic panel, such as the firm's BioFire Film Array line — which Willemsen noted had an installed base of 4,500 units at the end of the first quarter this year — this could further shorten the time to diagnosis. The FilmArray Blood Culture Identification (BCID) assay, for example, tests for 27 pathogens that can cause sepsis, including three common antibiotic resistance markers, and has a run time of about one hour. The firm has also purportedly been developing a lower respiratory tract infection panel for which it is conducting a clinical trial.
Mark Miller, bioMérieux's chief medical officer, noted that the company also develops stewardship-related companion assays in partnership with pharmaceutical companies developing new antibiotics.
For example, it has a line of gradient tests that give the minimum inhibitory concentration of an antibiotic needed to inhibit growth of cultured bacteria, called Etests. It also develops companion tests on its Vitek 2 system, an automated system that performs biochemical microbial identification and antibiotic susceptibility testing. "We collaborate with drug companies so that the launch of the antibiotic and the launch of the Etest go together, so that clinicians are able to do testing in the lab and have confidence in using the antibiotics," Miller said, adding that just about every new antibiotic that is launched globally is paired with one of the firm's tests.
bioMérieux is also participating in an evaluation called the infection-Carbapenem Resistance Evaluation Surveillance Trial, or iCREST, in Europe in partnership with AstraZeneca. The trial is both an epidemiological research project to determine the prevalence of carbapenem-resistant infections and an assessment of a new combination antibiotic — ceftazidime and avibactam — developed by AstraZeneca and Allergan to treat serious antibiotic-resistant infections. AstraZeneca will use bioMérieux’s chromID CARBA SMART chromogenic culture media and two types of bioMérieux Etest strips: ceftazidime/avibactam and meropenem, as a comparator.
Lab workers have highlighted that speed and accuracy of assays are particular requirements for adoption of sepsis-related testing. Similarly, getting information out as quickly as possible is now also part of the stewardship push with all of bioMérieux's products, Miller said.
In addition to Virtuo and FilmArray, this would include the Vitek MS MALDI-TOF mass spec system, which performs automated identification testing within minutes.
Some diagnostics manufacturers, such as Cepheid and Accelerate Diagnostics, for example, are also focusing marketing efforts on antibiotic stewardship with products for hospital acquired infections and identification and susceptibility testing.
However, "There aren't many companies that have so many pieces that address one particular problem," Miller said.
New indications for PCT
bioMérieux's PCT piece, meanwhile, has evolved over the past few years to include specific indications to aid in stewardship decisions.
PCT has been used off-label for some time to distinguish viral from bacterial infections, most commonly in Europe. Thermo Fisher Scientific has non-exclusively licensed PCT tests from its subsidiary Brahms to a number of firms, including Roche, Abbott, DiaSorin, FujireBio, Samsung, and Siemens. In addition to co-licensing and co-marketing relationships, Thermo Fisher also manufactures at least three PCT tests under its own brand.
Roche's Elecsys BRAHMS PCT is an electrochemiluminescence immunoassay for the determination of procalcitonin in human serum or plasma on the automated Roche Elecsys, Modular, and Cobas e immunoassay analyzers. bioMérieux's Vidas BRAHMS PCT test runs on the fully automated Vidas instrument, while Thermo's BRAHMS PCT sepsis test is an immunoassay.
Both Roche and bioMérieux have obtained FDA claims for using their PCT assays for sepsis. The two tests were cleared for marketing in the US last year to project 28-day mortality risk to sepsislike symptoms. Essentially, this was a prognostic indication, where an 80 percent drop in PCT levels on day four compared to day one when the patient began treatment would indicate that treatment was proceeding successfully and mortality at 28 days should be reduced.
bioMérieux had also previously approached the FDA for additional indications, Miller said.
"We recognized that there was a lot of literature out there [showing] that procalcitonin could be used to target those patients that did not have a bacterial infection and did not need antibiotics — so [the PCT test] had a very important negative predictive value," he said, noting that some 50 to 60 percent of patients get antibiotics at admission for what turn out to be viral infections. After an extensive global literature review, the firm presented its findings to the FDA and obtained clearance. The stewardship claims — which the firm notes are distinct from other company's PCT claims at this time — allow bioMérieux's test to be used to determine when it is appropriate to start and stop antibiotics for suspected pneumonia, and when to stop antibiotics in patients with sepsis.
With the latter, for example, when a patient's PCT level drops to more than 80 percent, "you can actually stop their antibiotics safely, thereby reducing the exposure of antibiotics in the ICU, which is a huge place for generating antibiotic resistance," Miller said.
In patients who present with suspected pneumonia, the firm showed that the PCT test can reduce antibiotic use by between 20 and 40 percent in the overall population — "which is huge," Miller said, given, for example, that the National Action Plan to Combat Antibiotic-Resistant Bacteria suggests reducing antibiotic use by 20 percent. "Here, with a single biomarker, you can probably do more than that."
The claims for the VIDAS BRAHMS PCT were also "really groundbreaking" for other reasons, he added. "It was the first time that a biomarker has ever been approved by the FDA for managing antibiotics and for using antibiotics appropriately." It was also one of the first times the agency has approved claims based on literature alone.
bioMérieux's time as the only player with antibiotic management claims may be limited, however, as it would seem that all of the Thermo Fisher licensees share similar core technology. On the other hand, a non-BRAHMS PCT test from Diazyme was cleared in April to aid in diagnosis and prognostication of sepsis progression, but that test has a specific warning against its use in antibiotic therapy decision making.
Willemsen highlighted that bioMérieux currently has "the vast majority" of the PCT market in the US, "because bioMérieux was the first company to have a claim on PCT, together with Brahms, the company that developed it," and he reiterated that only the bioMérieux VIDAS assay is approved by the FDA for antibiotic management.
However, "Now we have newcomers already in, or willing to enter, the market," he said. To his mind this is advantageous. "It means that more people are going to use it, that the awareness is growing. We have worked very hard in the last four years, when we were basically alone in this market, to promote VIDAS PCT and to go to every hospital that we have access to and explain the benefits of it."
Indeed, clinicians seem to have been receiving the stewardship messages, and some have already seen advantages to PCT testing.
For example, some are "incredibly aware of the relationship to overuse and misuse of antibiotics and the development of Clostridium difficle colitis," said Daniel Feinstein, director of the medical surgical intensive care unit at Cone Health in Greensboro, North Carolina.
Feinstein, who authored an opinion piece last week on the benefit of PCT testing to combat superbugs, said antibiotic stewardship is a crucial priority for all doctors, and "PCT is a strong piece to this fight."
His own use of the PCT test in his hospital has led to reductions in antibiotic use with no harm to patients, he said, as well as an overall reduction in antibiotic usage in the ICU since implementing a protocol following PCT values.
Feinstein said his hospital uses bioMérieux's test because it has higher upper limits of measurement, allowing doctors to understand the peaks and reductions in values with treatment more accurately. More importantly, past studies that use bioMérieux's PCT specifically and that show validity are important, and it is preferable to not use "a substitute that has not been studied well."
bioMérieux is now pursuing the possibility of bundling stewardship-related approaches and instruments in its sales strategies. "Hospitals are interested in looking at solutions much more than buying individual kits, and we're much more interested in selling solutions," Miller said. Willemsen pointed out that the US system of supplying to hospitals sometimes involves group purchasing organizations that offer large, integrated delivery networks that supply many locations. The company has been discussing bundling stewardship solutions with these customers, he said. "They can promote solutions to their member hospitals that include several pieces of the bioMérieux portfolio."
For hospitals that make individual purchasing decisions, the company is also addressing different constituents and customer groups that tend to use a subset of the firm's instruments, such as talking about blood culture and Vitek in the microbiology lab, or discussions of FilmArray with physicians. The "C-suite" of the hospital is also becoming more important, as they are subject to new cost controls and need to manage a budget. "Talking to these people about the positive effect on their readmissions and on use of antibiotics that our products can provide is another important channel to promote the use of those systems," said Willemsen.
Miller also pointed out the essential role diagnostics can play in cutting healthcare costs. "The old figures [saying that] about 70 percent of decisions in medicine are made on diagnostics but only 3 to 4 percent of healthcare expenses are in diagnostics are probably still true today," he said. "Diagnostics are undervalued and underutilized, but they have tremendous potential if used properly, and I think stewardship is one of the best examples of that."