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What to D.O.: Reject Strep-versus-Virus Paradigm for Personalized Approach to Pharyngitis Patients

Schell, Elizabeth; Pescatore, Richard, DO

doi: 10.1097/01.EEM.0000546143.17664.c0
What to D.O

Dr. Pescatore is the director of emergency medicine research for the Crozer-Keystone Health System in Chester, PA. He is also the host with Ali Raja, MD, of the podcast EMN Live, which focuses on hot topics in emergency medicine: http://bit.ly/EMNLive. Follow him on Twitter @Rick_Pescatore, and read his past columns at http://bit.ly/EMN-Pescatore. Ms. Schell is a second-year medical student at Drexel University College of Medicine in Philadelphia. Follow her on Twitter @LizSchell923.

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The cases I find most fascinating in the emergency department are those where the more I learn, the less confident I am in my diagnosis and treatment. Nothing better exemplifies this paradox than the patient presenting with a sore throat.

It's an incredibly common patient complaint—1.8 million will leave our doors each year with the diagnosis of pharyngitis, and nearly a third of them will test positive for Group A strep (GAS). (CDEM; http://bit.ly/2JPYgEA.) As a medical student, it was easy to dichotomize this population into those with strep and those without—the presumably 66 percent of whom were suffering from viral pharyngitis.

The minority who tested positive for GAS would receive the much-sought antibiotic prescription, with my medical school textbooks and early strep exams assuring me that antibiotics would prevent the much-feared complications of streptococcal pharyngitis—the molecular mimicry leading to rheumatic heart disease, renal injury, or any number of suppurative infectious disasters.

As a resident insatiably consuming FOAM and cutting-edge emergency medicine literature, I developed a nihilistic approach to the patient with sore throat. Online and traditional sources alike began to challenge the paradigm of the risk of rheumatism and the benefits of antibiotics. Medical myth-busters suggested that the original concepts of antibody cross-reactivity and our role in preventing it were rooted in poorly-done and probably irrelevant studies conducted in the mid-20th century. (Circulation 1971;43[6]:915; http://bit.ly/2JUvZfR.)

The near-eradication of rheumatic fever from developed countries and the antigenic shift of common GAS bacteria supported a minimalistic approach to antibiotic treatment of strep throat. With no compelling evidence of benefit and clear risks of allergy and adverse drug reactions, the guideline-supported dichotomization of pharyngitis—antibiotics for GAS and no antibiotics for any other cause—simplified in my mind to an even more barebones approach: no testing, no antibiotics, and no fear of rheumatic bogeymen or mythical antigenic injury.

With time, experience, and even more exploration of data, though, I've come to appreciate pharyngitis as a more complex clinical conundrum than a simple separation of strep and viruses or antibiotics v. neglect. A growing literature base suggests that GAS is not the only bacterium that should be of concern in pharyngitis. Fusobacterium necrophorum (FN) was found in 23 percent of pharyngitis cases (Clin Infectious Diseases 2009;49[10]:1467; http://bit.ly/2JYyQV8), and is the causative bacteria in Lemierre syndrome and may be the leading cause of peritonsillar abscess. (Eur J Clin Microbiol Infect Dis 2008;27[8]:733; http://bit.ly/2JTOpxi.)

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FN v. GAS Pharyngitis

Robert Centor, MD, (of Centor Criteria fame) found in one cross-sectional study of students 15-30 years old, that FN pharyngitis was more common than strep pharyngitis and clinically resembled GAS pharyngitis. (Ann Intern Med 2015;162[4]:241; http://bit.ly/2JV2uKS.)

With no rapid diagnostic test yet developed for FN—and it will likely be years before such a test becomes widely available in EDs—perhaps we should have a higher index of suspicion for non-GAS bacterial causes of pharyngitis. Even then, the evidence on whether FN is truly a pathogenic bacterium or a normal flora not meriting routine antibiotic coverage is conflicted. FN has been found in throat swabs of up to 76 percent of asymptomatic controls (PLoS ONE 2018;13[1]: e0189423; http://bit.ly/2JUwOFt), but one study didn't find FN in any of its 100 control subjects. (J Med Microbiology 2004;53[Pt 10]:1029; http://bit.ly/2JTUMki.)

Regardless of one's threshold for antibiotic therapy, however, there remains a bewildering variation in antimicrobials employed. High rates of clindamycin, azithromycin, amoxicillin/clavulanate, and even doxycycline have been reported in the literature. Current guidelines recommend a 10-day course of penicillin to treat GAS pharyngitis, but multiple investigations have shown that amoxicillin is more commonly prescribed to all age groups. It tends to taste better than penicillin, and can be dosed once daily instead of twice daily like penicillin—which makes it an appealing alternative in children—but amoxicillin adds unnecessary exposure to broader-spectrum coverage and increased cost.

That small price difference on the individual patient level compounded over millions of prescriptions for pharyngitis, however, amounts to more than $4 million each year. When used as empiric therapy without a confirmed bacterial cause for pharyngitis, amoxicillin also risks the classic reaction of mononucleosis, one of the certain downsides of antibiotic use.

The strep-versus-virus dichotomy of sore throat represents a simplistic approach that ignores the real risk of non-GAS bacteria and their associated complications. With our evolving understanding of pharyngitis and its microbial milieu, the decision for applying antibiotics is more complex than the binary framework suggested by guidelines and the framework I once formed in medical school and more nuanced than the nihilistic attitude borne from more recent discussions.

We should eschew the strep-versus-virus paradigm in favor of a more considered and personalized approach to the patient with pharyngitis, with due consideration for non-GAS bacteria and, barring compelling reasons for substitution, provision of penicillin instead of broader agents when empiric therapy is deemed appropriate.

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