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Ideas and Opinions |

Expand the Pharyngitis Paradigm for Adolescents and Young Adults

Robert M. Centor, MD
[+] Article, Author, and Disclosure Information

From the University of Alabama at Birmingham, Huntsville, Alabama.

Potential Conflicts of Interest: None disclosed.

Requests for Single Reprints: Robert M. Centor, MD, Huntsville Regional Medical Campus, University of Alabama at Birmingham, 301 Governors Drive, Huntsville, AL 35801; e-mail, rcentor@uab.edu.

Ann Intern Med. 2009;151(11):812-815. doi:10.7326/0003-4819-151-11-200912010-00011
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Current guidelines and review articles emphasize that clinicians should consider group A β-hemolytic streptococcus in the diagnosis and management of patients with acute pharyngitis. Recent data suggest that in adolescents and young adults (persons aged 15 to 24 years), Fusobacterium necrophorum causes endemic pharyngitis at a rate similar to that of group A β-hemolytic streptococcus. On the basis of published epidemiologic data, F. necrophorum is estimated to cause the Lemierre syndrome—a life-threatening suppurative complication—at a higher incidence than that at which group A streptococcus causes acute rheumatic fever. Moreover, these estimates suggest greater morbidity and mortality from the Lemierre syndrome. The diagnostic paradigm for adolescent pharyngitis should therefore be expanded to consider F. necrophorum in addition to group A streptococcus. Expanding the pharyngitis paradigm will have several important implications. Further epidemiologic research is needed on both F. necrophorum pharyngitis (especially clinical presentation) and the Lemierre syndrome. Clinicians need reliable diagnostic techniques for F. necrophorum pharyngitis. In the meantime, adolescents and young adults who develop bacteremic symptoms should be aggressively treated with antibiotics for F. necrophorum infection. Physicians should avoid macrolides if they choose to treat streptococcus-negative pharyngitis empirically. Finally, pediatricians, internists, family physicians, and emergency department physicians should know the red flags for adolescent and young adult pharyngitis: worsening symptoms or neck swelling (especially unilateral neck swelling). Adolescent and young adult pharyngitis is more complicated than previously considered.





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Keep Lemierre's syndrome in the back of your mind.
Posted on December 8, 2009
Ahmad Kaako
University of Tennessee, College of Medicine, Chattanooga
Conflict of Interest: None Declared

Based on a recent serious case of a sore throat we have seen in our facility (1), I concur with the importance of the spreading the awareness among health care providers and the ER physicians about Lemierre's syndrome and expanding the pharyngitis paradigm for young patients. Being one of the critical care team residents that time, I had the chance to take care of that young patient who presented with a simple complaint of sore throat then was complicated with serious life threatening issues. I keep that diagnosis in the back of my mind every time I see young patient with atypical presentation of sore throat. From my perspective, I believe that anecdotal evidence also has a significant role in practice change because the source of practice change was not only based on medical literature but also related to that anecdotal event.


(1) A sore throat--potentially life-threatening? Li HY, Grubb M, Panda M, Jones R. J Gen Intern Med. 2009 Jul;24(7):872-5. Epub 2009 May 10.

Conflict of Interest:

None declared

Expand the pharyngitis paradigm for adolescents and young adults
Posted on December 28, 2009
Professor Em. Marc De Meyere
Department of General Practice and Primary Health Care, University of Ghent, Belgium
Conflict of Interest: None Declared
To the editor, Robert Centor published an interesting article about the management of pharyngitis for adolescents and young adults (1). The data about the Lemierre syndrome oblige us to be vigilant, but we cannot agree with his conclusions especially as formulated in his second key summary point Use a penicillin or a cephalosporin for empirical treatment of rapid streptococcus-negative pharyngitis in adolescents and young adults. In his article, Centor mentions that we do not have data on the clinical presentation of F.necrophorum pharyngitis: Whether antibiotic therapy affects the duration and severity of pharyngitis symptoms or contagion is unknown, so these considerations cannot be included as a rationale for diagnosis and treatment. Nevertheless, without scientific evidence, Centor recommends to treat the 30% of the adolescents and young adults who present with at least 3 of the following symptoms: fever, tonsillar exudates, swollen tender anterior cervical adenopathy, or lack of cough.

In this era of evidence-based-medicine, it is surprising that an author can recommend such a management no clinical trial is realized to prove that this management is effective, which side-effects can be expected, and what are the possible consequences for rate of resistance and the costs for the community and the patient.

Surprising in a good sense, we found an alternative recommendation at the end of the article. Students and residents must learn the natural history of routine pharyngitis: resolution in 3 to 5 days. This is a basic option in more and more guidelines in Europe (2) and apparently even in North America. On the other hand, when disease does not resolve quickly, symptoms worsen, or unilateral neck swelling develops, physicians should consider an expanded differential diagnosis, including suppurative complications (peritonsillar abcess and the Lemierre syndrome). In those patients, physicians should obtain blood cultures and include clindamycin or penicillin-metronidazole We can agree with this management.

Attending clinical trials on this topic, including the Lemierre syndrome, it does not seem necessary to invent a new paradigm- nor to change the management of pharyngitis - even for adolescents and young adults.


1.Centor R. Expand the pharyngitis paradigm for adolescents and young adults. Ann Intern Med 2009;151:812-15.

2.Matthys J.,De Meyere M. et al. Differences among international pharyngitis guidelines: not just academic. Ann Fam Med 2007;5:436-43.

Conflict of Interest:

None declared

Changes in treatment strategies for acute pharyngitis may be premature
Posted on January 11, 2010
Alan L. Bisno, MD. MACP
University of Miami Miller School of Medicine, Miami, FL and University of Tennessee Health Science
Conflict of Interest: None Declared

The provocative Perspective article of Dec. 1, 2009 by Dr. Robert Centor (1) calls attention to the potential etiologic role of Fusobacterium necrophorum (Fn) in acute pharyngitis in adolescents and young adults. We question whether current data are adequate to support Centor's recommendations regarding changes in the treatment of pharyngitis in this age group. Citing recent studies from Europe reporting isolation rates of Fn of 10% from throat swabs, Centor concluded that Fn may cause 6000 cases of pharyngitis per one million adolescents per year. Whether Fn asymptomatically colonizes the oropharynx is not clear (2), but a recent Danish study (3) used real-time PCR to show that 21% of normal control subjects harbored Fn in the pharynx. Thus, we do not necessarily agree that isolation of Fn from a throat swab of a sore throat patient equates to causation. Establishing Fn as a causative agent of acute pharyngitis would minimally require the demonstration of a specific host immune response following isolation or identification of Fn during a symptomatic infection.

Given current knowledge, we think that two of Centor's recommendations are at best premature. The first is that adolescents and young adults with at least three of the Centor clinical criteria (fever history, tonsillar exudates, cervical adenitis, or lack of cough) (4) should receive empiric antimicrobial therapy. Based upon data in Centor's original report (5), we estimate that this strategy would result in empiric treatment of 60% of patients with non-group A streptococcal (GAS) pharyngitis. The proportion of these patients actually infected with Fn is at present simply unknown. The second recommendation is to abandon macrolides in treatment of acute pharyngitis in adolescents and young adults. This recommendation is not terribly controversial because at present macrolides are recommended only as one option in treatment of penicillin-allergic individuals. Nevertheless, many primary care providers find them useful for this indication because macrolide-resistant GAS is still rare in the US.

Like Centor, we are intrigued by the recent reports suggesting that Fn could be a significant cause of acute pharyngitis in adolescents and young adults. We urge that more definitive studies be performed before endorsing or adopting substantive changes in antimicrobial practice. If implemented now, such changes will undoubtedly lead to considerable excessive antimicrobial therapy of cases of viral pharyngitis in the age group for which they are recommended.


(1) Centor RM. Expand the pharyngitis paradigm for adolescents and young adults. Ann Intern Med 2009; 151(11):812-815.

(2) Riordan T. Human infection with Fusobacterium necrophorum (Necrobacillosis), with a focus on Lemierre's syndrome. Clin Microbiol Rev 2007; 20(4):622-659.

(3) Jensen A, Hagelskjaer KL, Prag J. Detection of Fusobacterium necrophorum subsp. funduliforme in tonsillitis in young adults by real- time PCR. Clin Microbiol Infect 2007; 13(7):695-701.

(4) Centor RM, Allison JJ, Cohen SJ. Pharyngitis management: defining the controversy. J Gen Intern Med 2007; 22(1):127-130.

(5) Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the emergency room. Med Decis Making 1981; 1(3):239-246.

Conflict of Interest:

ALB is a member and past chairman of the IDSA guideline committee on streptococcal pharyngitis.

Re:Expand the pharyngitis paradigm for adolescents and young adults
Posted on January 14, 2010
Robert M. Centor
UAB, Huntsville Regional Campus
Conflict of Interest: None Declared

To the Editor:

Matthys presents a rationale for not changing the pharyngitis paradigm for adolescents and young adults. I disagree, but perhaps did not make the point clear enough.

Our current paradigm has us focus solely on whether or not patients have a group A beta hemolytic streptococcal pharyngitis. I am suggesting that we should expand the paradigm to worry about Fusobacterium necrophorum pharyngitis also.

What are the implications of a new paradigm? We who study pharyngitis have an obligation to learn more about Fusobacterium necrophorum pharyngitis. Only through more knowledge might we prevent patients from the morbidity and mortality that can occur from that infection. Currently we encourage early diagnosis of Lemierre syndrome, but we would prefer preventing the syndrome. Only through a paradigm change will we collect the appropriate data to understand how to prevent the syndrome. Perhaps we will have better culture techniques; perhaps we will develop rapid tests; perhaps we can identify the infection based on clinical signs and symptoms. Regardless, expanding the paradigm will refocus our thinking about adolescent and young adult pharyngitis. I believe that my article makes that case convincingly.

Matthys excellent review of pharyngitis guidelines focuses on the acute sore throat and does not mention the natural history or an approach to evaluating patients whose symptoms worsen (1). Adding such a recommendation is a paradigm expansion. We should both teach this concept and add this consideration to textbooks and guidelines.

In critiquing my recommendations, Matthys raises the controversy concerning empiric antibiotics for adolescent and adult pharyngitis. This controversy persists despite the controversy having only a minor impact on unnecessary antibiotic use. Along with co-authors I have previously addressed this issue in a perspective (2). In that perspective we suggested that the empiric treatment of patients with 3 or more of the 4 signs and symptoms would only result in 7.5% of adolescents and young adults receiving antibiotic treatment without having either Group A beta strep or Group C beta strep pharyngitis.

Linder has shown that the problem of inappropriate antibiotic use would decrease dramatically if physicians would just avoid giving antibiotics to patients having 2 or less of the predictive signs and symptoms (3). In a decision analysis, we found that the decision between treating empirically and treating only rapid test positive patients was a "toss up (4)."

My main point though was that physicians should not use macrolides for empiric treatment in this age group. While I favor empiric therapy for this subset of patients, I specifically acknowledge that some physicians will rationally choose to not use empiric therapy.

For over 50 years, group A beta hemolytic streptococcus has occupied focus of pharyngitis evaluation. Unless we include Fusobacterium necrophorum as a potentially dangerous consideration, we will not make progress in either preventing Lemierre syndrome or at least making earlier diagnoses of this potential lethal complication.


1. Matthys J, De Meyere M, Van Driel M, De Sutter A. Differences Among International Pharyngitis Guidelines: Not Just Academic. The Annals of Family Medicine. 2007;5:436-443.

2. Centor R, Allison J, Cohen S. Pharyngitis Management: Defining the Controversy. J GEN INTERN MED. 2007;22:127-130.

3. Linder JA, Chan JC, Bates DW. Evaluation and treatment of pharyngitis in primary care practice: the difference between guidelines is largely academic. Arch Intern Med. 2006;166:1374-1379.

4. Singh S, Dolan JG, Centor R. Optimal management of adults with pharyngitis - a multi-criteria decision analysis. BMC Med Inform Decis Mak. 2006;6:14.

Conflict of Interest:

None declared

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