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Getting Strep Pharyngitis Right


An Expert Interview With Stanford Shulman MD


Laurie Scudder, DNP, NP, Stanford T. Shulman, MD

Nov 09, 2012Authors & Disclosures


Editors' Recommendations


Sore Throats Mostly Viral, Not Strep


Editor's Note:

The Infectious Diseases Society of America (IDSA) has just released a 2012 update of the Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis, its first update in 10 years.[1] Acute pharyngitis is common -- and most episodes, the guideline emphasizes, are not due to group A streptococcus (GAS). That does not, however, mean that patients with non-GAS pharyngitis are not receiving antibiotics. In fact, inappropriate treatment of acute pharyngitis with antibiotics is a major contributor to the rising incidence of antimicrobial resistance. Two articles just published in Archives of Internal Medicine document the continuing problem of overprescribing of antibiotics for viral infections.[2,3] In an invited commentary in Archives, Ralph Gonzales, MD, MSPH, Director of the Program in Implementation and Dissemination Sciences at the University of California, San Francisco, argued that the continuing high rate of antibiotic use is the result of a failure to translate evidence into practice.[4] Medscape spoke with Stanford Shulman, MD, lead author of the IDSA guideline and Professor of Pediatric Infectious Diseases at Northwestern University's Feinberg School of Medicine, about the evidence underpinning this new guideline and its usefulness in helping clinicians to translate this important guideline into practice.

Examining the Evidence


Medscape: Can you briefly review the process used by the guideline authors to evaluate evidence from the last 10 years when developing the updated guideline?


Dr. Shulman: The guideline committee carried out a comprehensive review of the published literature since release of the last document in 2002. Individual members of the guideline committee searched publications related to all topics to be included within the guideline. We included careful evaluation of a Cochrane review that had been published recently related to this topic.[5] We reviewed guidelines of other organizations who make recommendations related to this topic as well to make sure that we understood the nature of other organizational guidelines.


Medscape: Can you describe the strength of the evidence?


Dr. Shulman: I think the evidence is reasonably strong in most situations but certainly not all.

Diagnostic Recommendations


Medscape: The guideline strongly emphasizes the need to confirm a diagnosis of GAS and not to rely on clinical suspicion. The authors then go on to list the signs and symptoms that suggest a viral or bacterial etiology. However, the guideline notes that scoring systems based on clinical signs and symptoms are relatively poor predictors of the presence or absence of GAS. Is there any scenario in which treatment based on clinical suspicion alone is appropriate?


Dr. Shulman: The guideline does provide a list of symptoms that are commonly associated with GAS infections of the throat in addition to a list of separate signs and symptoms related to viral pharyngitis. Having laid out those signs and symptoms that are often present with GAS, it is still clear that those signs and symptoms are not sufficiently reliable or accurate to allow diagnosis of streptococcal pharyngitis to be made on clinical suspicion alone. There are simply too many false positives and some false negatives. With respect to the viral signs and symptoms, patients who have rhinorrhea, cough, mouth ulcers, and hoarseness are very unlikely to have bona fide streptococcal pharyngitis. So we can rely upon their presence to conclude on clinical grounds that the patient does not have a streptococcal pharyngitis and testing is not really indicated.


Is there any scenario in which treatment could be based on clinical suspicion alone? I think that there are a few circumstances where the epidemiology would suggest this is reasonable. For example, if one child in a family has signs and symptoms suggestive of strep and the diagnosis is then confirmed in that child, and a sibling or someone else in the household in short order presents with an identical or very similar clinical illness, it would be reasonable to assume that the same pathogen is in the household and the likelihood of that second child having streptococcal pharyngitis as well would be extremely high. That would be a scenario in which clinical suspicion would enable one to make a diagnosis.


Medscape: The guideline notes that rapid antigen detection tests (RADTs) have sufficient specificity for clinicians to make a decision to treat patients with a positive RADT. However, sensitivity is not ideal, and, therefore, negative RADTs in children, but not adults, should prompt clinicians to obtain a backup throat culture. Is this recommendation applicable to all clinical situations? What about situations where the RADT is obtained despite a clinical suspicion of a viral etiology in order to reassure an anxious parent? Can clinicians reasonably use an RADT to confirm a suspected viral etiology for pharyngitis?


Dr. Shulman: Unfortunately, what one intuitively might think is a very simple situation -- we either have a virus or we have a strep infection and it shouldn't be so complicated -- can become very complicated. The answer to your question is: no. If the clinical clues are all pointing towards a viral etiology, relying upon a rapid test or a culture can be very misleading. This gets us into a discussion of the very complicated problem of the chronic streptococcal carrier. There are many children, and a considerable number of young adults as well, who become at various times colonized in the throat with GAS that does not cause an infection in the sense of making the patient ill. Carriage in chronic carriers persists many months -- 6 and even 12 months has been documented. If the individual who is a chronic carrier gets a cold and has a throat swab done, the throat swab will be positive. A rapid test and even a culture cannot reliably distinguish between a person who has a bona fide streptococcal pharyngitis and one who is a chronically colonized individual who now has an intercurrent viral illness. You can't distinguish those individuals. So, it's really not recommended to do any testing if the clinician really believes that all the signs and symptoms point towards a virus.

What About Carriers?


Medscape: The identification and management of a suspected GAS carrier is one of the thorniest issues discussed in the guideline, which concludes that these individuals need not be identified or treated as they are unlikely to be infectious or to develop GAS complications. However, as you have clearly illustrated, unidentified carriers presenting with acute viral pharyngitis do end up being treated with antibiotics even if the clinician suspects a viral etiology. Is there any evidence that clinicians should attempt to eradicate the carrier state?


Dr. Shulman: On a routine basis, we believe the carrier state is not a serious issue that warrants attempts to eradicate it except in highly selected circumstances such as if there is a history of someone with rheumatic fever in the household and you do not want to have a carrier in the household. In general, it is not necessary. However, the scenario you posed earlier gets to the issue of how does one really establish the diagnosis of a GAS carrier? The patient who comes in with enough symptoms to raise the clinical suspicion of a possible streptococcal pharyngitis should be tested with a rapid test and/or throat culture. If positive, the patient should be treated. A common scenario is a child who, within a brief period of time, say a couple of months, after that initial episode, has repeated illnesses that have prompted throat swabs that are repeatedly positive. That raises the clinical suspicion that perhaps this is a child who really is not having bona fide streptococcal pharyngitis over and over again but may be a chronic streptococcal carrier.


One way to try to clarify that situation is to wait until this child is asymptomatic and in a normal state of health. Then, culture the patient at that point in time. Finding GAS in the throat of the asymptomatic child at that point pretty much clinches the diagnosis of the chronic streptococcal carrier. That can make it easier to deal with future episodes of sore throat. Knowing that a child or an adult is a chronic streptococcal carrier should alter the indications to swab in the future. If a patient who is known to be a carrier has marginal symptoms -- not really highly suggestive of a streptococcal pharyngitis -- that would be a circumstance where it is probably wise not to do any kind of testing. If, however, a child who is a chronic carrier comes in with every symptom that strongly points towards a possible streptococcal pharyngitis, you want to err on the side of caution. You should do a swabbing and testing of that particular child. But I think that you want to use a different scale in terms of whose throat you want to swab and test when you know a patient is a streptococcal carrier.


Medscape: And to clarify -- this is quite different from a recommendation to culture as a test of cure.


Dr. Shulman: That is correct. While some could argue it is similar to a test of cure, it is in very selected patients and very selective circumstances.


Medscape: Should a carrier be cultured subsequently to determine if the carrier state is still present?


Dr. Shulman: There has never been a recommendation that one should do that. There might be selective situations, depending on the epidemiology; for example, a household with someone who is at particularly high risk of acquiring GAS from the carrier -- even though in general we view carriers to be not at all highly contagious. Carriers seem to be at very little risk to themselves in terms of developing complications of strep and at very low risk to their contacts. They do not seem to shed organisms efficiently, in contrast to someone who has a bona fide infection with presumably higher numbers of strep cells that are more actively replicating and more metabolically active and more easily transmitted from patient to patient.



Treatment Recommendations


Medscape: Can you speculate as to why antibiotic therapy for acute pharyngitis remains so common?


Dr. Shulman: I think that is a really interesting question. If you have sit-down discussions with various pediatric practices, you find great variance in how commonly antibiotic therapy for acute pharyngitis is prescribed. Sometimes this occurs with no testing done, which we would consider to be quite inappropriate. Other times, testing is performed very frequently and patients with viral symptoms who are very likely to be carriers are indeed being treated over and over again. In some practices, the expectation has grown over time among the parents of the children in the practice that a child who is sick with a fever needs to come in to get an antibiotic. Generating that expectation among the patient/parent population then leads to real disappointment on the part of parents who bring their child in sick expecting an antibiotic and are told that one is not needed.


In contrast, other practices have assiduously worked to change the expectations of parents. There is a lot of lay literature about the major problem of antibiotic-resistant organisms in our society and the contribution of antibiotic overuse to that problem. In some practices, highly sophisticated parents come in, and -- in contrast to other group of parents -- you have to talk these parents into allowing their child to get a course of antibiotics when that's indicated.


What that tells me is, number one, parents obviously vary in their degree of sophistication about this issue. We can, as practitioners, try to educate them about the fact that antibiotics are great when they are needed, but they are not so great when not needed because they can induce antibiotic-resistant organisms, which are bad for the individual patient and bad for society. It may be faster to just write a prescription and send a family out the door. It takes a few extra minutes to explain why that would not be in the child's best interest. Over time, if I take those extra minutes, that will change the expectations of the parent population.


Medscape: The 2012 guideline reiterates the recommendation made in the 2002 guideline for use of penicillin or amoxicillin as first-line therapy for GAS pharyngitis in patients not allergic to these agents, a recommendation based on strong, high-quality evidence. Do data indicate that these agents are indeed used as a first choice by clinicians? What about recommendations for penicillin-allergic individuals? What agents are most appropriate?


Dr. Shulman: There are a few individuals in our country who have argued fairly strenuously that cephalosporins should be considered as first-line therapy for GAS pharyngitis in nonallergic patients. In areas where those folks have been quite vocal and influential, there is more cephalosporin use than in other areas. When I lecture to large groups of pediatricians and have asked for a show of hands about their first-line antibiotic choice for GAS pharyngitis, by far penicillin and especially amoxicillin have been the most commonly reported recommendations by pediatricians. In the family practice community, we don't have really up-to-date, scientifically sound surveillance on this point.


There is a new wrinkle related to amoxicillin in this guideline that I think is quite important. There are now 5 published clinical studies that demonstrate that single-daily-dose amoxicillin is highly efficacious for treatment of streptococcal pharyngitis if given for 10 full days.[6-10] It is as effective as 3- to 4-times-a-day penicillin or 2- to 3-times-a-day cephalosporins. Having the ability to give a once-daily dose of amoxicillin makes it very convenient to administer. Amoxicillin suspension tastes pretty good, so for young children that is a benefit as well. It should be emphasized that there are absolutely no GAS strains resistant to those drugs -- not a single one has ever been identified when tested in vitro against penicillin or amoxicillin. The same thing is true for cephalosporins -- no resistance whatsoever.


With respect to penicillin-allergic patients, erythromycin was a first-line recommendation in the past. That drug causes a fair amount of gastric distress. Erythromycin has been eliminated from the current guideline and replaced by azithromycin or clarithromycin, which are equivalent in their activity to erythromycin but much better tolerated.


However, there is some resistance to macrolide antibiotics among GAS. It varies from year to year and from geographic site to geographic site. On average in the United States, 5%-8% of GAS strains are macrolide resistant, at least in the studies that we've done, which are now a few years out of date.[11] But it fluctuates widely, and in real practice a clinician treating a penicillin-allergic patient with strep throat is not going to know the sensitivity of that particular child's strep to this class of antibiotics. That information is not going to be available on a real-time basis. Often, it can only be obtained by specifically asking the microbiology lab to test the organisms, and that takes several days and is not very practical.


So, having said that, the recommendations for the penicillin-allergic patient do include clarithromycin and azithromycin. I should highlight that the approved dosing for azithromycin in this situation is 12 mg/kg/day once a day for 5 days. Azithromycin is essentially the only agent that is given in a 5-day course as opposed to a 10-day course for all the other agents.


In addition, clindamycin for 10 days is highly efficacious, and the resistance rate of GAS to clindamycin is around 1%.[11]


The other potential recommendation for the penicillin-allergic individual is a first-generation cephalosporin with the caveat that you should not administer any cephalosporin to someone who has anaphylactic-type penicillin allergy that includes hives, wheezing, or frank anaphylaxis. If the symptoms attributed to penicillin allergy include only a mild rash of uncertain consequence but not hives, it should be fine to administer a cephalosporin in that situation. Cefadroxil, a first-generation cephalosporin, can be given once daily for 10 days.


Medscape: Can you review the recommendations for ancillary treatment with other pharmacologic and nonpharmacologic agents? Is there any role for surgery?


Dr. Shulman: There have been some publications in the last decade that have studied the potential adjunctive value of steroids in treating streptococcal pharyngitis. Our guideline does not endorse the use of steroids even in brief regimens. The trials are less than ideally performed, and our assessment is that the putative benefit is marginal at best. Because GAS pharyngitis is a self-limited illness, symptoms resolve quickly with antibiotic therapy, even more quickly than they do spontaneously. It is hard to demonstrate significant benefit from steroids. So we do not believe that they should play a role.


On the other hand, nonsteroidal medications could be administered for a short period of time to relieve high fever and severe discomfort and buy some time for the antibiotic to work. We do not believe that that should be a common and routine recommendation but one that should be individualized. I should also note the caveat that we do not recommend the administration of salicylate (aspirin) to children in this circumstance.


With respect to surgery, there has been much discussion and consideration of tonsillectomy as an intervention in the patient who is having apparent recurrent GAS pharyngitis episodes. The largest and best performed study from Pittsburgh conducted in patients who were thought to have recurrent GAS pharyngitis demonstrated a transient benefit with somewhat fewer pharyngitis episodes in the posttonsillectomy patients, but that benefit was only seen for a year.[12] After that year, the frequency of pharyngitis in the tonsillectomized and nontonsillectomized groups was essentially the same.


We also are concerned that many patients who are thought to have recurrent GAS pharyngitis are, in fact, the carriers we spoke about earlier who are having recurrent viral illnesses rather than having recurrent bona fide GAS pharyngitis. In any case, we do not feel that this particular surgical intervention is warranted except in very selected circumstances. Therefore, the guideline states that tonsillectomy should not be performed for the sole indication of recurrent streptococcal pharyngitis.





Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55:e86-e102. http://cid.oxfordjournals.org/content/early/2012/09/06/cid.cis629.full.pdf+html Accessed September 25, 2012.


Zhang Y, Steinman MA, Kaplan CM. Geographic variation in outpatient antibiotic prescribing among older adults. Arch Intern Med. 2012;172:1-7. http://archinte.jamanetwork.com/article.aspx?articleid=1362924 Accessed September 25, 2012.


Fairlie T, Shapiro DJ, Hersh AL, Hicks LA. National trends in visit rates and antibiotic prescribing for adults with acute sinusitis. Arch Intern Med. 2012;172:1513-1514.


Gonzales R, Ackerman S, Handley M. Can implementation science help to overcome challenges in translating judicious antibiotic use into practice? Arch Intern Med. 2012;172:1471-1473.


van Driel ML, De Sutter AIM, Keber N, Habraken H, Christiaens T. Different antibiotic treatments for group A streptococcal pharyngitis. The Cochrane Library. 2010. http://onlinelibrary.wiley.com/doi/10.1002

/14651858.CD004406.pub2/abstract;jsessionid=42C4D6A10E51E1B5D005209BA386E455.d03t03 Accessed October 22, 2012.


Feder HM Jr, Gerber MA, Randolph MF, Stelmach PS, Kaplan EL. Once-daily therapy for streptococcal pharyngitis with amoxicillin. Pediatrics. 1999;103:47-51. Abstract


Gerber MA, Tanz RR. New approaches to the treatment of group A streptococcal pharyngitis. Curr Opin Pediatr. 2001;13:51-55. Abstract


Clegg HW, Ryan AG, Dallas SD, et al. Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin: a noninferiority trial. Pediatr Infect Dis J. 2006;25:761-767. Abstract


Lennon DR, Farrell E, Martin DR, Stewart JM. Once-daily amoxicillin versus twice-daily penicillin V in group A beta-haemolytic streptococcal pharyngitis. Arch Dis Child. 2008;93:474-478. Abstract


Shvartzman P, Tabenkin H, Rosentzwaig A, Dolginov F. Treatment of streptococcal pharyngitis with amoxycillin once a day. BMJ. 1993;306:1170-1172. Abstract


Tanz RR, Shulman ST, Shortridge VD, et al. Community-based surveillance in the United States of macrolide-resistant pediatric pharyngeal group A streptococci during 3 respiratory disease seasons. Clin Infect Dis. 2004;39:1794-1801. Abstract


Paradise JL, Bluestone CD, Colborn DK, Bernard BS, Rockette HE, Kurs-Lasky M. Tonsillectomy and adenotonsillectomy for recurrent throat infection in moderately affected children. Pediatrics. 2002;110:7-15. Abstract






Edited by Mayzoo
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There is a lot of good information in this article. Of particular important to PANDAS parents and pediatricians is the info about drug resistance and abx preference. The only problem I see w/ this article is w/ pediatricians and their likelihood of thinking these guidelines would also apply to PANDAS kids. It does mention RF kids but I'd assume not many pediatricians relate the two conditions.


Came back to add, you can access the entire original journal publication, Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America, by clicking on the link in the first reference.

Edited by nicklemama
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