BARCELONA, Spain – Nearly 10 years ago, former UK Prime Minister David Cameron commissioned economist Lord Jim O'Neill to compile a report on the rapidly growing global threat of antibiotic resistance.
Jointly sponsored by the UK government and the Wellcome Trust, that report was published in May 2016. Among its several main findings and recommendations, which have since been widely disseminated, was a call to promote new, rapid diagnostic tests to reduce the unnecessary use of antibiotics.
At the European Society of Clinical Microbiology and Infectious Diseases global congress (ESCMID Global) held here this week, O'Neill, former commercial secretary of the UK Treasury and chief economist for Goldman Sachs, joined clinicians and scientists to discuss progress made since the report and review remaining challenges as part of a symposium sponsored by Marcy l'Étoile, France-based international diagnostics firm BioMérieux.
O'Neill's report at the time estimated that approximately 700,000 deaths annually worldwide could be attributed to antimicrobial resistance, and predicted that number could balloon to 10 million people per year by 2050 if no coordinated actions were taken to mitigate the problem.
The good news, O'Neill noted at the symposium, is that there have been signs of progress — some of it related to public policy, and some of it not. For instance, he said, in a phenomenon he and his colleagues have referred to as the "Shake Shack effect," some antibiotic resistance overuse, particularly in the US, has been curbed by the growing desire by consumers to avoid factory-farmed meats.
In addition, the United Nations General Assembly plans to hold a high-level meeting on AMR this September, which should serve to retrain the spotlight on the issue. Nevertheless, O'Neill noted, the topic is not in the news cycle nearly enough. "Antimicrobial resistance needs its own Greta Thunberg or, when it comes to new antibiotics or drugs, its own Elon Musk," he said, noting that the issue needs more attention in order to pressure policymakers to initiate change.
His specific message to the symposium attendees, however, was that their work in researching, developing, and promoting the use of new, rapid diagnostic technologies remained imperative.
"At the time of that review, we learned that even if we get new antibiotics, [they will fail] unless we use them better — we say 'access not excess' — as too many places get them too easily and administer them too readily," O'Neill said. "We need a permanent reduction in treating these things like sweets."
He also proposed that the healthcare system needs to start embracing everyday modern technologies like smartphones "to help medical professionals know, rather than an educated guess, whether an antibiotic is needed, and if so, what kind of antibiotic. Why is technology in general not being made central in our health systems to empower physicians to show patients immediately: 'You don't need an antibiotic, here's the evidence'?"
The phrase "educated guess" came up frequently in the presentations of other scientists and clinicians during the symposium.
According to Romney Humphries, professor of pathology, microbiology, and immunology and director of the infectious disease laboratory and division of laboratory medicine at Vanderbilt University Medical Center, physicians in general mostly still pick antibiotics for patients mostly with educated guesses based on available data, "and do a pretty good job."
Nevertheless, for something like sepsis, the standard of care has a median turnaround time of nearly 60 hours.
The ideal test, she said, would identify both the organism and provide antibiotic resistance information at the point of care. "We are not anywhere close to that, but we have made lots of progress," she said.
For antibiotic resistance testing, current marketed solutions generally fall into two buckets: pathogen and resistance gene identification, and rapid phenotypic antimicrobial resistance testing (AST). "The first can be extremely fast but you're only detecting what you're looking for, and are available for only a very limited number of the thousands of resistance genes we might see in a day at our hospital," she said. Rapid phenotypic AST, meanwhile, can provide testing of several drug classes in anywhere from three to eight hours.
As previously reported by 360Dx, the market for these tests has been slowly recovering after the COVID-19 pandemic halted much of the momentum it had gained since the O'Neill report and diverted attention away from the issue.
BioMérieux has attempted to position itself at the front and center of this recharged market, dedicating approximately three-quarters of its R&D funding and making multiple acquisitions over the years to help solve the AMR issue, resulting in platforms like the BioFire BCID2 Panel — which tests positive blood culture samples for 43 targets associated with bloodstream infections including 10 antimicrobial resistance genes — and the Vitek Reveal rapid phenotypic AST system acquired along with Specific Diagnostics in 2022.
Patience and communication
Humphries' presentation focused on the use of rapid diagnostic testing for bloodstream infections, which have a greater sense of urgency than the more mundane example of patients visiting their physicians with general symptoms of a respiratory infection, for instance, and seeking answers and treatment.
In these situations, the risk of fostering additional AMR resistance through inappropriate use of antibiotics is just as high, but there is not the same level of mortality risk.
Physicians and their patients may benefit in these cases from using syndromic testing panels such as BioMérieux's BioFire Respiratory 2.1 panel, a highly multiplexed real-time PCR assay for 22 common respiratory pathogens that runs on the company's FilmArray systems.
The turnaround time for assays like these is about an hour, which the company frames as sufficient for providing information to physicians in real time to help diagnose their patients. But in practice, running panels like these takes much longer than an hour, especially if a sample is sent to a central laboratory for testing. And, the reality of modern healthcare is that busy patients are meeting with their busy doctors on average for just a few minutes.
In a pre-symposium media briefing, Humphries chalked this up to a general societal problem. "People need to be a little more patient," she said.
Céline Pulcini, a professor of infectious diseases at the Université de Lorraine in France, echoed this idea during the briefing, noting that "when an infection is not severe, we need to be patient. If I knew that I didn't have a bacterial infection, I wouldn't want antibiotics [given] the side effects," not to mention the potential contribution to the AMR problem.
Pulcini further noted that testing alone, in a vacuum, cannot solve the AMR crisis.
"Antimicrobial stewardship is a larger process than just the testing," she said. "We need better communication to physicians as to how to use the information wisely."
In her presentation, Pulcini focused on her work developing and evaluating what she calls "indicators and dashboards," including clinical decision support systems (CDSS), which she said are promising in the battle against AMR, "but a lot still needs to be done" to overcome system and economic constraints.
"One of the many problems we face in daily practice is we have too many data and data sources. Information technology tools are needed to help us," she said, harkening back to O'Neill's comments on empowering physicians with technological tools to help them more effectively make use of test results.
CDSS, however, are not easy to design and implement, Pulcini noted, with many different IT systems operating in parallel and a lack of standardization among the problems plaguing the field. She also noted that machine learning is a promising tool in this area, but that needs high-quality data from many sources and settings to develop accurate systems.
BioMérieux has been active in this area, as well, according to Céline Roger-Dalbert, executive VP of R&D at the company. In an emailed statement, Roger-Dalbert noted that the company offers "a comprehensive suite of IT solutions including CDSS, which facilitate laboratory workflow management, dashboards, quality indicators, and clinical decision-making. Our Vision suite featuring Clarion and Maestria plays a pivotal role in laboratories to manage data [and] analytics."
Meanwhile, for molecular-specific solutions, the company's Fireworks and Syndromic Trends dashboard "[support] the centralization of data from decentralized testing and provide tools to evaluate, at the local, regional, and global levels, epidemiologic trends in pathogens or resistance markers prevalence," Roger-Dalbert said.
Finally, she noted, BioMérieux also recently acquired Canadian CDSS developer Lumed, whose software can "help clinicians evaluate treatment options taking into consideration the local hospital data, the scientific literature, and guidelines."
True point of care
In a separate BioMérieux-sponsored symposium at ESCMID Global, Andrew Meltzer, an associate professor at the George Washington School of Medicine & Health Sciences and a practicing emergency medicine doctor, discussed top-level results of studies by his group and others demonstrating that while the information provided by panel tests may provide some peace of mind to patients, it does not necessarily change behavior in terms of prescribing antibiotics.
For instance, he cited one prominent study published in JAMA Network Open in 2022 that multiplex PCR point-of-care testing for respiratory pathogens did not reduce the overall prescribing of antibiotics in the emergency department (27.3 percent in the intervention group versus 28.5 percent in the control group) in a randomized clinical trial of more than 1,200 children.
In his own group's study, the results of which have not been published, there was a very slight but statistically insignificant change in antibiotic prescribing behavior of physicians when patients were tested with the BioFire respiratory panel.
"It takes time for provider behavior to change," Meltzer said. "These antibiotic prescriptions are often made right during the discussion with patients, and you really need to have that information when you have that conversation."
To that end, Meltzer and colleagues, along with BioMérieux, have embarked on another study to assess the effectiveness of the company's relatively new Spotfire point-of-care molecular testing platform, which received US Food and Drug Administration clearance and CLIA waiver last year alongside a syndromic respiratory panel called SpotFire R, which detects 15 common viral and bacterial respiratory pathogens. Just last month, the company also received FDA clearance and CLIA waiver for an updated test called the BioFire SpotFire Respiratory/Sore Throat (R/ST) panel.
The new study, called "Rapid Diagnosis of Viral Acute Respiratory Infection to Decrease Unnecessary Antibiotic Utilization in the Emergency Department" (RADIATE), aims to enroll 200 patients who visit the emergency department with complaints related to acute respiratory illness. These patients will be administered the SpotFire R test as part of their diagnostic work-up to see if the results of the test provide physicians with more timely, accurate information to potentially reduce the use of unnecessary antibiotics.
At the ESCMID Global symposium, Meltzer shared some very early data from this study, noting that researchers have thus far only enrolled 36 participants over the course of several weeks. So far, a little over half of tested patients had a viral infection according to the panel, and importantly, there has been no antibiotic utilization in these cases — a stark contrast to prior studies examining the use of a panel with a 60-minute-or-longer turnaround time. Meltzer said that the researchers have also seen a high level of satisfaction from patients and providers.
In her email, BioMérieux's Roger-Dalbert said that the new testing system and panels "allow healthcare providers at primary care or urgent care facilities to determine the causative agent of a patient's respiratory symptoms and decide if antimicrobial treatment is necessary during the patient's visit."
She further noted that the company "aims to fully leverage the new Spotfire technology to broaden testing in point-of-care settings. Panels for gastrointestinal infection, sexually transmitted infection, and women's health are being considered for their potential to enhance patient care during visits. This could significantly aid in prescribing the appropriate antibiotics by identifying the pathogen or co-infections and detecting common resistance markers associated with these infections."