With respiratory season upon us, emergency departments and urgent care centers will soon be admitting patients with Influenza-Like Illness, a medical diagnosis based on symptoms alone. In most cases, treatment will likewise be based solely on symptoms; however, treatment decisions can and should be informed by diagnosis, even in time-sensitive situations.
Empirical treatment of ILI has been an accepted and even recommended practice for decades, but it can jeopardize not only patients' outcomes, but also the viability of the medicines used to treat them. The problem of empirical treatment in relation to antimicrobial resistance is twofold. Patients with ILI are often treated with antibiotics, even though the most common cause for this set of symptoms is influenza, a viral infection. Alternatively, these patients are often automatically prescribed with influenza antivirals, which will be unnecessary if influenza is not the cause of infection and are optimally effective for influenza-infected patients only if administered within 48 hours of onset of symptoms.
In both scenarios, over-prescribing contributes to the growing public health crisis of AMR, which by 2050 is expected to kill more people in the world than cancer and diabetes combined.1 The problem is not limited to antibiotics. Many strains of influenza have already developed resistance to the older class of flu antivirals, the adamantanes. After four decades of effective use in the prophylaxis and treatment of influenza, global resistance to these drugs has increased dramatically among influenza viruses of the A/H3N2 subtype in recent years.2
The new class of influenza antivirals, the neuraminidase inhibitors oseltamivir and zanamivir, are currently suitable for all strains. However, sporadic resistance has already been observed with oseltamivir. During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide.3 During the 2009 flu pandemic, further reports of resistance occurred.
In response to growing problem of AMR, the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria issued a report in 2015 calling for the "establishment of antibiotic stewardship programs in all acute care hospitals and improved antibiotic stewardship across all healthcare settings."4 For acute care settings, a key component of this strategy should be the implementation of routine rapid point-of-care testing of admitted patients.
Traditionally, the "gold standard" of influenza screening has been viral culture or polymerase chain reaction; however, these methods do not deliver results quickly enough to be useful in selecting treatment options.5 In recent years, rapid molecular POC tests have been introduced that detect influenza and other viral and bacterial infections with lab-caliber accuracy in an actionable timeframe – as quickly as 8 minutes – facilitating immediate linkage to appropriate treatment or other clinical interventions. The availability of results during a patient visit has a direct impact on the use of antibiotics: research has shown that physician awareness of a rapid diagnosis of influenza decreases antibiotic use.6 Rapid diagnosis has also been shown to reduce hospitalizations, length of hospital stays, follow-up tests, and complications, thereby optimizing outcomes and reducing transmission of the virus. 7,8,9
During respiratory season, these issues become even more urgent because a range of seasonal viral and bacterial infections, notably, influenza and Respiratory Syncytial Virus, can present with similar symptoms yet require vastly different interventions. For example, because there is no approved treatment for RSV, the most common cause of severe respiratory illness such as bronchiolitis in children under two, infection control strategies are focused on reducing transmission – especially among vulnerable infants. Rapid testing can expedite the identification of RSV-infected children so that they can be separated from RSV-negative patients in the same ward or on the same floor. This is critically important because even though children with RSV infections typically recover in 1-2 weeks, many can continue to spread the virus for up to 3 weeks.10
Cases of Group A Streptococcus also peak during respiratory season, and overuse of antibiotics in the treatment of GAS has also contributed to alarming trends in resistance. GAS has developed resistance to clindamycin and to the macrolide class of drugs, including erythromycin, azithromycin and clarithromycin. Each year in the United States, erythromycin-resistant, invasive GAS causes 1,300 illnesses and 160 deaths.11 Unfortunately, in cases of suspected GAS infection, antibiotics are prescribed in 55% to 75% of cases, while GAS is confirmed in only 15% to 30% of these cases.12 Rapid identification and consequent prompt treatment of patients with pharyngitis due to GAS can reduce the risk of spread, can allow patients to return to school or work sooner, and may reduce the acute morbidity of this illness.13
Today, molecular platforms detect influenza, GAS and RSV infection with lab-caliber accuracy in an actionable timeframe – enabling providers to immediately link patients to appropriate treatment, withhold antibiotics as needed, and to implement other infection control measures. As a class, molecular tests exceed lab culture in sensitivity, partly due to the susceptibility of culture methods to virus loss, corruption, or inactivation during transport.
When it comes to diagnosing respiratory infections, hospital-based healthcare providers have traditionally had to choose between speed and performance when procuring diagnostics, because available tests offered only one or the other. Today, they can demand – and obtain – both, improving both the care and outcomes of their patients.
Norman Moore, PhD, is the scientific director of infectious disease for Alere. Dr. Moore plays an integral role in Alere's antimicrobial stewardship campaign (Test Target Treat™), which focuses on educating healthcare professionals on the role of rapid diagnostics in enabling improved treatment decisions as a way to combat the antibiotic resistance crisis.
Dr. Moore holds multiple patents and was the original inventor of the rapid urinary antigen tests for Legionella and S. pneumonia, among other assays. He has served on multiple National Institute of Allergy and Infectious Diseases (NIAID) grant committees, the Centers for Disease Control and Prevention (CDC) guideline group for rapid influenza testing, the Clinical Laboratory Standards Institute guideline committee for point-of-care infectious disease testing, and the College of American Pathology Point-of-Care Committee. Most recently, Dr. Moore was appointed to the Expert Panel on Point-of-Care Testing for the Clinical and Laboratory Standards Institute (CLSI). He is a frequent speaker at industry events and publishes widely on topics related to antibiotic stewardship and point-of-care testing for infectious diseases.
Dr. Moore received his Bachelor's Degree in biology and philosophy from Dartmouth College and his Ph.D. in microbiology from the University of New Hampshire.
1 O'Neill, J. Tackling drug-resistant infections globally: Final report and recommendations. The Review on antimicrobial resistance. May 2016.
2 Nelson MI, et al. The origin and global emergence of adamantine resistant A/H3N2 influenza viruses. Virology. 2009;388:270-278.
3 Dharan NJ, et al. Infections with oseltamivir-resistant influenza A (H1N1) virus in the United States. JAMA. 2009;301(10):1034-41.
4 The White House, Washington. National Action Plan for Combating Antibiotic-Resistant Bacteria. March 2015.
5 Bonner AB, et al. Impact of the rapid diagnosis of influenza on physician decision-making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial. Pediatrics. 2003;112(2):363-7.
6 Bonner AB, et al.
7 Blaschke AJ, Shapiro DJ, Pavia AT, et al. A national study of the impact of rapid influenza testing on clinical care in the emergency department. J Ped Infect Dis. 2014;3(2):112–118; doi: 10.1093/jpids/pit071. First published online November 13, 2013
8 Williams KM, Jackson MA, Hamilton M. Rapid diagnostic testing for URIs in children: impact on physician decision making and cost. Infect Med. 2002;19(3):109–111.
9 Bonner AB, Monroe KW, Talley LI, Klasner AE, Kimberlin DW. Impact of the rapid diagnosis of influenza on physician decision making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial. Pediatrics. 2003;112(2):363–367.
10 Centers for Disease Control (CDC): About RSV - Infection and Incidence. [Online]. Available from: http://www.cdc.gov/rsv/about/infection.html. Accessed: September 14, 2016.
11 The White House, Washington. National Action Plan for Combating Antibiotic-Resistant Bacteria. March 2015.
12 Maltezou, H.C. et al. (2008) Evaluation of a rapid antigen detection test in the diagnosis of streptococcal pharyngitis in children and its impact on antibiotic prescription. Journal of Antimicrobial Chemotherapy, 62:1407–1412.
13 Gerber, M.A. and Shulman, S.T. (2004) Rapid Diagnosis of Pharyngitis Caused by Group A Streptococci. Clin Microbiol Rev. 2004 Jul; 17(3). Doi 10.1128/CMR.17.3.571-580.2004.
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