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Viral, bacterial diagnostics bolster antimicrobial stewardship
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Numerous viral and bacterial respiratory illnesses have overlapping symptoms. In many cases, it can be difficult for pediatricians to determine what a child should be diagnosed with, which can affect how the child is medically treated.
According to the CDC, at least 30% of antibiotics prescribed in the outpatient setting are inappropriately prescribed. Research presented at IDWeek last year suggested that approximately 14% of antibiotic prescriptions for children were made for respiratory conditions that did not require antimicrobial therapy. Experts have warned that unnecessary use of antibiotics contributes significantly to antimicrobial resistance.
Numerous tests have been developed for the purpose of differentiating between viral and bacterial illnesses and to ensure that patients are treated correctly. Distinguishing patients who need antibiotics from those who do not could promote antimicrobial stewardship in outpatient settings, according to experts.
“Identifying someone in the early stages of a viral infection can assist in containing or stopping the spread of a particular infection,” Rob Sambursky, MD, president and CEO of RPS Diagnostics, told Infectious Diseases in Children. “It can also prevent physicians from giving someone antibiotics that the patient does not need and contribute to antibiotic misuse.”
What tests are available?
According to P. Gigi Chawla, MD, MHA, chief of general pediatrics at Children’s Minnesota, pediatricians face several challenges when attempting to differentiate between bacterial and viral illnesses in their patients, including patient and parent expectations of diagnosis and treatment, the clinician’s time, the clinic’s lab capabilities and the expenses of running diagnostic tests. Moreover, some testing recommendations are conflicting.
“There is a lot of guidance available for clinicians, and I think there are a lot of mixed messages that clinicians get,” she told Infectious Diseases in Children. “There are situations where testing is not recommended, like for bronchiolitis, so there are also questions about whether we should be testing in the first place.”
Anupama Kalaskar, MD, a pediatric infectious disease consultant at Children’s Minnesota, told Infectious Diseases in Children that the type of tests pediatricians use depends on the setting — outpatient clinics or small town hospitals vs. larger hospitals — and the epidemiology of the pathogen.
“For example, rapid tests for influenza have been around for quite some time,” Kalaskar said. “The ability of rapid influenza diagnostic tests (RIDTs) to detect the virus is highly dependent on whether influenza is actively circulating in the community, or if it is the beginning of the season and there is not a lot of influenza going around. Additionally, there can be a lot of variability in the sensitivity of these tests depending on the platform used. Therefore, the FDA reclassified RIDTs with more stringent minimum performance requirements in 2017.”
In its most recent guideline update, the Infectious Diseases Society of America shifted its focus away from RIDTs and emphasized the importance of newer and highly accurate molecular tests — such as nucleic acid amplification tests (NAATs).
Kalaskar said infectious disease diagnostics have “really expanded in the last 5 years or so, and tests — mainly in the form of NAATs, such as real-time PCR-based tests — have been used more often.”
According to Kevin Outterson, JD, the N. Neal Pike Scholar in Health and Disability Law at Boston University and executive director at CARB-X — a nonprofit organization supporting the development of diagnostics, therapeutics and vaccines — more than 100 diagnostic technologies for viral and bacterial infections are in development, but it is difficult to pinpoint how many of these tests will make it to market and later be used in the pediatric health care setting.
Tests of the future
In a 2016 study, researchers from the Imperial College London showed that the presence of two genes — IFI44L and FAM89A — were able to predict bacterial infections with 100% accuracy.
Michael Levin, FRCPCH, professor of pediatrics at Imperial College London and co-author of the study, told Infectious Diseases in Children that this method of determining whether an infection is bacterial or not is “a long way from having a cheap, reliable, validated test which could be put in every hospital.”
One of the barriers to its development, he said, is that point-of-care tests are easier to develop when a test is identifying a protein compared with genes.
“Gene-based tests are more technically challenging to turn into a rapid test suitable to be used in EDs everywhere, but they are likely to be more accurate,” he said. “I think there have been a number of studies similar to ours using gene signatures that show they are likely to work.”
Most research to date, according to Sambursky, has focused on molecular testing.
“There are many problems with molecular testing,” he said. “You use these tests to identify pathogens in a very sensitive way. On one hand, this is fantastic, but you overidentify colonizing bacteria or viruses that are not necessarily causing a specific condition.”
Instead, he suggested that researchers should focus on the identification of important pathogen-associated systemic host response protein biomarkers that can distinguish between viral and bacterial infections. Sambursky’s company developed the FebriDx, a single-use, point-of-care test for acute upper respiratory infections that detects elevated levels of Myxovirus resistance protein A and C-reactive protein directly from finger-stick whole blood. He said it represents an easier approach to assess the host immune response, with a sensitivity of 95%, a specificity of 94%, and negative predictive value of 99% in febrile patients.
The test is not approved for use in the United States, but it recently launched in the European Union.
Moving forward, Levin theorized that future research will be focused on gene testing, but this would require biotechnology companies to develop a device that is both rapid and cost-effective.
In addition, Kalaskar said that once a new test is developed in the U.S., it must first be cleared by the FDA before clinical labs can adopt and validate it for use in children. This can be a lengthy process.
“The issue is that it takes time from development of the test until it can actually be used in a practical way in the clinical setting,” she said.
Barriers to use
Outterson told Infectious Diseases in Children that although better diagnostics could promote improved antibiotic use, there are barriers to their development and use.
“The difficulty is that once you develop a diagnostic device, you need the funding to finish clinical trials and then get regulatory approvals. However, this is not the last step,” he said. “You then have to convince payers to cover the test and providers to use it. You need to make a commercial case about its benefits. It is a daunting process, which explains why few companies are in the diagnostic space.”
Additionally, Kay Roy, PhD, MRCP, MB ChB, a consultant physician in respiratory and general internal medicine at West Hertfordshire Hospitals NHS Trust, England, told Infectious Diseases in Children that pressure from within the medical community may impact whether these tests are used.
“As point-of-care testing becomes more widely applied and accepted in the clinical arena, physicians will become more responsible for patient testing,” she said. “In the future, this will become more common. This influences a shift in health care delivery systems where lab tests are brought to the bedside.”
Roy added that physicians are leading a service that is traditionally and conventionally led within the lab, causing “some degree of apprehension from pathology services,” but effective patient management relies on improved communication and integrated decision-making processes between all specialties.
Outterson said that “a lot of hard work and diligence” are behind successful tests that are adopted into practice by physicians and trusted by patients.
‘In a perfect setting’
According to research published in Open Forum Infectious Diseases, 41 million antibiotic prescriptions are made every year, and approximately 90% of these are for acute respiratory infections. The researchers stressed that the development and widespread use of tests for viral and bacterial infections have the potential to reduce diagnostic uncertainty, pressure from patients and parents and the misuse of antibiotics.
The reduction of antibiotic misuse is of particular importance, with the CDC reporting at least 2 million antibiotic-resistant infections in the U.S. every year.
Chawla said pediatricians need tests that are cost-effective, deliver high-quality results and optimize clinics’ efficiency. She said it is challenging for outpatient practices to keep up with the pace of updating technology and educating staff to use this equipment. She suggested that a single test that could include multiple viruses and bacteria — like strep, pertussis, influenza and respiratory syncytial virus together — could optimize the diagnosis and treatment of patients but may be costly for patients and clinics.
Roy mentioned that tests like these, including the BioFire FilmArray multiplex PCR system (bioMérieux), are often employed in the lab setting but are simple enough to use in point-of-care. Specifically, the BioFire test has five panels that can detect numerous pathogens — including a respiratory panel, a gastrointestinal panel, a blood culture identification panel, a pneumonia panel, and a meningitis/encephalitis panel. She added that the ability to test for several different pathogens is an important step in maintaining antimicrobial stewardship efforts.
“Differentiating between viral and bacterial infections is honestly a lifelong challenge,” Chawla said. “It is certainly compounded by patients’ and parents’ expectations. They come in and want treatment, so I think from that standpoint, it moves all of us to find ways to differentiate viral and bacterial infections.” – by Katherine Bortz
- References:
- Bhattacharya S, et al. Sci Rep. 2017;doi:10.1038/s41598-017-06738-3.
- CDC: Antibiotic - Antimicrobial Resistance. https://www.cdc.gov/drugresistance/index.html. Accessed December 17, 2018.Fleming-Dutra KE, et al. JAMA. 2016;doi:10.1001/jama.2016.4151.
- Herberg JA, et al. JAMA. 2016;doi:10.1001/jama.2016.11236.
- Hersch A, et al. Abstract 170. Presented at: IDWeek 2018; Oct. 3-7, 2018; San Francisco.
- Joseph P, et al. Open Forum Infect Dis. 2018;doi:10.1093/ofid/ofy024.
- Oliver J, et al. PLoS Negl Trop Dis. 2018;doi:10.1371/journal.pntd.0006335.
- Rhedin S, et al. Pediatrics. 2014;doi:10.1542/peds.2013-2042.
- Shapiro N. et al. Ann Med. 2018:doi: 10.1080/07853890.2018
- Uyeki TM, et al. Clin Infect Dis. 2018;doi:10.1093/cid/ciy866.
- Zaas A, et al. Sci Transl Med. 2013;doi:10.1126/scietranslmed.3006.280.
- For more information:
- P. Gigi Chawla, MD, MHA, and Anupama Kalaskar, MD, can be reached at madeline.riggs@childrens.mn.org.
- Michael Levin, FRCPCH, can be reached at m.levin@imperial.ac.uk.
- Kevin Outterson, JD, can be reached at carbxpr@bu.edu.
- Kay Roy, PhD, MRCP, MB ChB, can be reached at kayroy2014@gmail.com.
- Rob Sambursky, MD, can be reached at sambursky@rpsdetectors.com.
Disclosures: Sambursky is an employee of RPS Diagnostics. Chawla, Kalaskar, Levin, Outterson and Roy report no relevant financial disclosures.