Clinical Infectious Diseases Advance Access published September 9, 2012
Clinical Practice Guideline for the Diagnosisand Management of Group A StreptococcalPharyngitis: 2012 Update by the InfectiousDiseases Society of Americaa Stanford T. Shulman,1 Alan L. Bisno,2 Herbert W. Clegg,3 Michael A. Gerber,4 Edward L. Kaplan,5 Grace Lee,6Judith M. Martin,7 and Chris Van Beneden8 1Department of Pediatrics, Division of Infectious Diseases, Ann & Robert H. Lurie Children’s Hospital, Northwestern University Feinberg School ofMedicine, Chicago, Illinois; 2Department of Medicine, University of Miami Miller School of Medicine, Miami Veterans Affairs Healthcare System,Miami, Florida; 3Department of Pediatrics, Hemby Children’s Hospital and Eastover Pediatrics, Charlotte, North Carolina; 4Department of Pediatrics,Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; 5Department of Pediatrics, University of Minnesota Medical School, Minneapolis,Minnesota; 6Division of Infectious Diseases, Boston Children’s Hospital, Boston, Massachusetts; 7Department of Pediatrics, University of Pittsburgh,Pittsburgh, Pennsylvania; and 8Respiratory Diseases Branch, National Center for Immunization and Respiratory Diseases, Centers for Disease Controland Prevention, Atlanta, Georgia The guideline is intended for use by healthcare providers who care for adult and pediatric patients withgroup A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of Americaguideline and discusses diagnosis and management, and recommendations are provided regarding antibioticchoices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations aremade for the penicillin-allergic patient, which now include clindamycin.
recommendations on the management of this verycommon clinical condition among adult and pediatric Group A streptococcal (GAS) pharyngitis is a signifi- patients. The guideline addresses issues related to the cant cause of community-associated infections. This diagnosis of streptococcal pharyngitis and its treatment document constitutes a revision of the 2002 guideline in patients who are or are not allergic to penicillin. The of the Infectious Diseases Society of America guideline does not discuss active surveillance testing or (IDSA) on the treatment of GAS pharyngitis other prevention strategies. Each section of the guide- The primary objective of this guideline is to provide line begins with a specific clinical question and is fol-lowed by numbered recommendations and a summaryof the most-relevant evidence in support of the recom- Received 3 July 2012; accepted 10 July 2012.
aIt is important to realize that guidelines cannot always account for individual mendations. Areas of controversy in which data are variation among patients. They are not intended to supplant physician judgment limited or conflicting and in which additional research with respect to particular patients or special clinical situations. IDSA considersadherence to these guidelines to be voluntary, with the ultimate determination is needed are indicated throughout the document and regarding their application to be made by the physician in the light of each pa- are highlighted in the Future Research section.
Summarized below are the recommendations made Correspondence: Stanford T. Shulman, MD, Department of Pediatrics, Division of Infectious Diseases, Ann & Robert H. Lurie Children’s Hospital, Northwestern in the updated guidelines for the diagnosis and man- University Feinberg School of Medicine, 225 E Chicago Ave, Chicago, IL 60611 agement GAS pharyngitis. The Panel followed a process used in the development of other IDSA guidelines, Clinical Infectious Diseases The Author 2012. Published by Oxford University Press on behalf of the Infectious which included a systematic weighting of the strength Diseases Society of America. All rights reserved. For Permissions, please e-mail: of recommendation (ie, “strong” or “weak”) and quality of evidence (ie, “high,” “moderate,” “low,” or “very IDSA Guideline for GAS Pharyngitis • CID • 1 low”), using the GRADE (Grading of Recommendations Diagnostic testing or empiric treatment of asymptomat- Assessment, Development, and Evaluation) system ic household contacts of patients with acute streptococcal (Table ). A detailed description of the methods, background, pharyngitis is not routinely recommended (strong, moderate).
and evidence summaries that support each of the recommenda-tions can be found in the full text of the guidelines. Specific treatment recommendations regarding streptococcal pharyngitis III. What Are the Treatment Recommendations for Patients Witha Diagnosis of GAS Pharyngitis? Patients with acute GAS pharyngitis should be treated with an appropriate antibiotic at an appropriate dose for a I. How Should the Diagnosis of GAS Pharyngitis Be Established? duration likely to eradicate the organism from the pharynx (usually 10 days). Based on their narrow spectrum of activity, Swabbing the throat and testing for GAS pharyngitis by infrequency of adverse reactions, and modest cost, penicillin rapid antigen detection test (RADT) and/or culture should be or amoxicillin is the recommended drug of choice for those performed because the clinical features alone do not reliably non-allergic to these agents (strong, high).
discriminate between GAS and viral pharyngitis except when Treatment of GAS pharyngitis in penicillin-allergic in- overt viral features like rhinorrhea, cough, oral ulcers, and/or dividuals should include a first generation cephalosporin (for hoarseness are present. In children and adolescents, negative those not anaphylactically sensitive) for 10 days, clindamycin RADT tests should be backed up by a throat culture (strong, or clarithromycin for 10 days, or azithromycin for 5 days high). Positive RADTs do not necessitate a back-up culture because they are highly specific (strong, high).
Routine use of back-up throat cultures for those with a IV. Should Adjunctive Therapy With Nonsteroidal Anti- negative RADT is not necessary for adults in usual circumstances, inflammatory Drugs (NSAIDs), Acetaminophen, Aspirin, or because of the low incidence of GAS pharyngitis in adults and Corticosteroids Be Given to Patients Diagnosed With GAS because the risk of subsequent acute rheumatic fever is generally exceptionally low in adults with acute pharyngitis (strong, moder- ate). Physicians who wish to ensure they are achieving maximal Adjunctive therapy may be useful in the management sensitivity in diagnosis may continue to use conventional throat culture or to back up negative RADTs with a culture.
If warranted, use of an analgesic/antipyretic agent such as Anti-streptococcal antibody titers are not recommend- acetaminophen or an NSAID for treatment of moderate to ed in the routine diagnosis of acute pharyngitis as they reflect severe symptoms or control of high fever associated with GAS past but not current events; strong, high).
pharyngitis should be considered as an adjunct to an appro-priate antibiotic (strong, high).
II. Who Should Undergo Testing for GAS Pharyngitis? Aspirin should be avoided in children (strong, moderate).
Adjunctive therapy with a corticosteroid is not recom- Testing for GAS pharyngitis usually is not recommended for children or adults with acute pharyngitis with clinical andepidemiological features that strongly suggest a viral etiology (eg, V. Is the Patient With Frequent Recurrent Episodes of Apparent cough, rhinorrhea, hoarseness, and oral ulcers; strong, high).
GAS Pharyngitis Likely to Be a Chronic Pharyngeal Carrier of Diagnostic studies for GAS pharyngitis are not indicated for children <3 years old because acute rheumatic fever is rare in children <3 years old and the incidence of streptococcal pharyn- We recommend that clinicians caring for patients with gitis and the classic presentation of streptococcal pharyngitis are recurrent episodes of pharyngitis associated with laboratory uncommon in this age group. Selected children <3 years old evidence of GAS pharyngitis consider that they may be experi- who have other risk factors, such as an older sibling with GAS encing >1 episode of bona fide streptococcal pharyngitis at infection, may be considered for testing (strong, moderate).
close intervals, but they should also be alert to the possibility Follow-up posttreatment throat cultures or RADT are that the patient may actually be a chronic pharyngeal GAS not recommended routinely but may be considered in special carrier who is experiencing repeated viral infections (strong, Strength of Recommendations and Quality of the Evidence change our confidence in theestimate of effect.
performed) is likely to have animportant impact on our confidencein the estimate of effect and islikely to change the estimate.
at least 1 critical outcome is veryuncertain.
unlikely to change our confidencein the estimate of effect.
of effect and is likely to change theestimate.
Information is based on GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria [–]Abbreviation: RCT, randomized controlled trial.
We recommend that GAS carriers do not ordinarily We do not recommend tonsillectomy solely to reduce justify efforts to identify them nor do they generally require the frequency of GAS pharyngitis (strong, high).
antimicrobial therapy because GAS carriers are unlikely tospread GAS pharyngitis to their close contacts and are at little or no risk for developing suppurative or nonsuppura-tive complications (eg, acute rheumatic fever; strong, GAS is the most common bacterial cause of acute pharyngitis, responsible for 5%–15% of sore throat visits in adults and IDSA Guideline for GAS Pharyngitis • CID • 3 Antibiotic Regimens Recommended for Group A Streptococcal Pharyngitis Children: 250 mg twice daily or 3 times daily; adolescents and adults: 250 mg 4 times daily or500 mg twice daily 50 mg/kg once daily (max = 1000 mg); alternate: <27 kg: 600 000 U; ≥27 kg: 1 200 000 U 20 mg/kg/dose twice daily (max = 500 mg/dose) 7 mg/kg/dose 3 times daily (max = 300 mg/dose) 7.5 mg/kg/dose twice daily (max = 250 mg/dose) Abbreviation: Max, maximum.
a See Table 1 for a description.
b Avoid in individuals with immediate type hypersensitivity to penicillin.
c Resistance of GAS to these agents is well-known and varies geographically and temporally.
20%–30% in children Accurate diagnosis of streptococ- antimicrobials to large numbers of patients with nonstrepto- cal pharyngitis followed by appropriate antimicrobial therapy is coccal pharyngitis. Such therapy unnecessarily exposes pa- important for the prevention of acute rheumatic fever; for the tients to the expense and hazards of antimicrobial therapy.
prevention of suppurative complications (eg, peritonsillar Despite improvements in antimicrobial prescribing for chil- abscess, cervical lymphadenitis, mastoiditis, and, possibly, other dren and adults with acute pharyngitis, a substantial number invasive infections); to improve clinical symptoms and signs; of patients continue to receive inappropriate antimicrobial for the rapid decrease in contagiousness; for the reduction in therapy Inappropriate antimicrobial use for upper re- transmission of GAS to family members, classmates, and other spiratory tract infections, including acute pharyngitis, has close contacts of the patient []; to allow for the rapid resump- been a major contributor to the development of antimicrobial tion of usual activities; and for the minimization of potential resistance among common pathogens Estimated econom- adverse effects of inappropriate antimicrobial therapy.
ic costs of pediatric streptococcal pharyngitis in the United Although acute pharyngitis is one of the most frequent ill- States range from $224 million to $539 million per year, in- nesses for which pediatricians and other primary care physi- cluding indirect costs related to parental work losses ].
cians are consulted, with an estimated 15 million visits per year In addition to acute disease, streptococcal pharyngitis is im- in the United States only a relatively small percentage of portant because it can lead to the nonsuppurative postinfec- patients with acute pharyngitis (20%–30% of children and a tious disorders of acute rheumatic fever with and without smaller percentage of adults) have GAS pharyngitis. Moreover, carditis, as well as to poststreptococcal glomerulonephritis. Al- the signs and symptoms of GAS and nonstreptococcal pharyn- though acute rheumatic fever is now uncommon in most de- gitis overlap so broadly that accurate diagnosis on the basis of veloped countries, it continues to be the leading cause of clinical grounds alone is usually impossible [ acquired heart disease in children in areas such as India, sub- With the exception of very rare infections by certain other Saharan Africa, and parts of Australia and New Zealand [].
bacterial pharyngeal pathogens (eg, Corynebacterium diphther- This guideline updates the 2002 practice guidelines of the iae and Neisseria gonorrhoeae) (Table antimicrobial IDSA [The following 5 clinical questions are addressed in therapy is of no proven benefit as treatment for acute pharyn- gitis due to organisms other than GAS. Therefore, it is ex-tremely important that physicians exclude the diagnosis of How should the diagnosis of GAS pharyngitis be GAS pharyngitis to prevent inappropriate administration of appropriate healthcare for specific clinical circumstances” [Attributes of good guidelines include validity, reliability, repro- ducibility, clinical applicability, clinical flexibility, clarity, multidis- ciplinary process, review of evidence, and documentation ].
A panel of 8 multidisciplinary experts in the management of streptococcal pharyngitis in children and adults was convened in 2009. The panel consisted of internists and pediatricians, including adult and pediatric infectious disease specialists and The group convened a face-to-face meeting in 2009 in which an outline of the guideline was discussed and the process of guide- line development using the GRADE approach was explained.
The GRADE approach offers a structured, systematic, and trans- parent process to formulate recommendations on the basis of explicit criteria that go beyond just the quality of available evi- dence (Table ) This was followed by a series of telecon- ferences in which a list of clinical questions to be addressed in the guideline was generated, discussed, and prioritized.
We identified up-to-date valid systematic reviews from the MEDLINE database, PubMed, and the Cochrane Library, and in selected cases we also reference lists of the most recent nar- rative reviews or studies on the topic. Unless specified other- wise, the search period was 1980–2012 and was restricted to the English-language literature. Articles were also retrieved by searches for clinical diagnosis, laboratory diagnosis, symptoms and signs, and microbiology. The panel members contributedreference lists in these areas. The quality of evidence was eval- Abbreviations: CMV, cytomegalovirus; EBV, Epstein-Barr virus; HIV, humanimmunodeficiency virus.
uated after the literature review. We based our judgments onthese systematic reviews and, if applicable, on additionalstudies published after the reviews were done. When system- Who should undergo testing for GAS pharyngitis? atic reviews were unavailable, we evaluated the original studies What are the treatment recommendations for patients to inform judgments about the quality of the underlying evi- dence that were based on examination of these studies.
Should adjunctive therapy with NSAIDs, acetamino- Primary key search terms were as follows: phen, aspirin, or corticosteroids be given to patients with a Is the patient with frequent recurrent episodes of ap- parent GAS pharyngitis likely to be a chronic pharyngeal “Practice guidelines are systematically developed statements to The Panel met on >4 occasions via teleconference (including assist practitioners and patients in making decisions about subgroup calls) and once in person to complete the work on IDSA Guideline for GAS Pharyngitis • CID • 5 the guideline. The purpose of the teleconferences was to Epidemiologic and Clinical Features Suggestive of discuss the questions, distribute writing assignments, and fi- Group A Streptococcal and Viral Pharyngitis nalize recommendations. All members of the Panel participat-ed in the preparation and review of the draft guideline.
Feedback was obtained from external peer reviews. The guide-line was reviewed and approved by the IDSA Standards and Practice Guidelines Committee (SPGC) and the IDSA Boardof Directors prior to dissemination.
All members of the expert panel complied with the IDSA policy regarding conflicts of interest, which requires disclosure of any financial or other interest that might be construed as • Anterior cervical adenitis (tender nodes) constituting an actual, potential, or apparent conflict.
Members of the expert Panel were provided a conflict of inter- • History of exposure to strep pharyngitis est disclosure statement from the IDSA and were asked toidentify ties to companies developing products that might beaffected by promulgation of the guideline. Information was re- quested regarding employment, consultancies, stock owner-ship, honoraria, research funding, expert testimony, and membership on company advisory committees. The Panel made decisions on a case-by-case basis about whether an indi- vidual’s role should be limited as a result of a conflict. No lim- At annual intervals, the Panel chair, the liaison advisor,and the SPGC chair will determine the need for revisions Routine use of back-up throat cultures for those with a to the updated guideline on the basis of an examination of negative RADT is not necessary for adults in usual circum- current literature. If necessary, the entire Panel will recon- stances, because of the low incidence of GAS pharyngitis in vene to discuss potential changes. When appropriate, the adults and the risk of subsequent acute rheumatic fever is gen- Panel will recommend full revision of the guideline to the erally exceptionally low in adults with acute pharyngitis IDSA SPGC and the IDSA Board of Directors for review (strong, moderate). Physicians who wish to ensure they are achieving maximal sensitivity in diagnosis may continue touse conventional throat culture or to back up negative RADTswith a culture.
Anti-streptococcal antibody titers are not recommended in the routine diagnosis of acute pharyngitis as they reflectpast but not current events (strong, high).
I. How Should the Diagnosis of Group A StreptococcalPharyngitis Be Established? Swabbing the throat and testing for GAS pharyngitis by Acute GAS pharyngitis has certain characteristic epidemiolog- rapid antigen detection test (RADT) and/or culture should ical and clinical features [, (Table The disorder is pri- be performed because the clinical features alone do not reli- marily a disease of children 5–15 years of age, and, in ably discriminate between GAS and viral pharyngitis except temperate climates, it usually occurs in the winter and early when overt viral features like rhinorrhea, cough, oral ulcers, spring. Patients with GAS pharyngitis commonly present with and/or hoarseness are present. In children and adolescents, sore throat (generally of sudden onset), pain on swallowing, negative RADT tests should be backed up by a throat culture and fever. Headache, nausea, vomiting, and abdominal pain (strong, high). Positive RADTs do not necessitate a back-up may also be present, especially in children. On examination, culture because they are highly specific (strong, high).
patients have tonsillopharyngeal erythema, with or without exudates, often with tender, enlarged anterior cervical lymph respiratory tract infection in children, but their respective nodes (lymphadenitis). Other findings may include a beefy, roles, if any, in causing pharyngitis are unknown ].
red, swollen uvula; petechiae on the palate; excoriated nares GAS is the most common cause of bacterial (especially in infants); and a scarlatiniform rash. However, pharyngitis, but other bacteria can also cause acute pharyngitis none of these findings are specific for GAS pharyngitis. Con- (Table ). Arcanobacterium haemolyticum is a rare cause of versely, the absence of fever or the presence of clinical features acute pharyngitis that may be associated with a rash similar to such as conjunctivitis, cough, hoarseness, coryza, anterior sto- that seen in scarlet fever, particularly in teenagers and young matitis, discrete intra-oral ulcerative lesions, viral exanthema, adults , ]. N. gonorrhoeae can occasionally cause acute and diarrhea strongly suggest a viral rather than a streptococcal pharyngitis in sexually active persons, and infections with other bacteria, such as Francisella tularensis and Yersinia en-terocolitica, and mixed infections with anaerobic bacteria (eg, Vincent’s angina) are rare causes of acute pharyngitis. Other There is broad overlap between the signs and symptoms of pathogens, such as Mycoplasma pneumoniae and Chlamydo- streptococcal and nonstreptococcal (usually viral) pharyngitis, phila pneumoniae, are uncommon causes of acute pharyngitis.
and the ability to identify streptococcal pharyngitis accurately Other bacterial causes of acute pharyngitis include groups C on the basis of clinical grounds alone is generally poor and G β-hemolytic streptococci and C. diphtheriae [ Therefore, except when obvious viral clinical and epi- Group C streptococcus (GCS) is a relatively common cause demiological features are present, a laboratory test should be of acute pharyngitis among college students and adults [].
performed to determine whether GAS is present in the In addition to endemic pharyngitis, GCS can cause epidemic pharynx , Efforts have been made to incorporate the food-borne pharyngitis after ingestion of contaminated prod- clinical and epidemiological features of acute pharyngitis into ucts, such as unpasteurized cow’s milk. Family and school out- scoring systems that attempt to predict the probability that a breaks of GCS pharyngitis have also been described. Even particular illness is caused by GAS pharyngitis [, though there are several well-documented food-borne outbreaks These clinical scoring systems are helpful in identifying pa- of group G streptococcal (GGS) pharyngitis, as well as a com- tients who are at such low risk of streptococcal infection that munity-wide respiratory outbreak of GGS pharyngitis in chil- performance of a throat culture or an RADT is usually unnec- dren [the etiologic role of GGS in acute, endemic essary. However, the signs and symptoms of streptococcal and pharyngitis remains unclear. Acute rheumatic fever has not nonstreptococcal pharyngitis overlap too broadly for diagnosis been described as a complication of either GCS or GGS phar- to be made with the requisite diagnostic precision on the basis yngitis. Reports have attempted to link acute glomerulonephritis of clinical grounds alone. Even subjects with all clinical fea- with GGS pharyngitis, but a causal relationship has not been tures in a particular scoring system can be confirmed to have established. Acute glomerulonephritis as a complication of GCS streptococcal pharyngitis only about 35%–50% of the time, pharyngitis is extremely unusual. Therefore, the primary reason and this is particularly the case in children ]. The clini- to identify either GCS or GGS as the etiologic agent of acute cal diagnosis of GAS pharyngitis cannot be made with certain- pharyngitis is to initiate antibiotic therapy that may reduce the ty even by the most experienced physicians, and bacteriologic clinical impact of the illness. Currently, there is no convincing evidence from controlled studies of a clinical response to antibi-otic therapy in patients with acute pharyngitis and either GCS Several recent reports have documented the isolation of Fu- common cause of acute pharyngitis (Table ) ]. Respiratory sobacterium necrophorum from throat swabs of adolescents viruses, such as adenovirus, influenza virus, parainfluenza and young adults with nonstreptococcal pharyngitis [–].
virus, rhinovirus, and respiratory syncytial virus, frequently Some studies also suggest a role for F. necrophorum in cases of cause acute pharyngitis. Other viral agents of acute pharyngitis recurrent or persistent pharyngitis (with or without bactere- include coxsackievirus, echoviruses, and herpes simplex virus.
mia or Lemierre’s syndrome) []. F. necrophorum is the caus- Epstein-Barr virus is a frequent cause of acute pharyngitis that ative agent of most cases of Lemierre’s syndrome, which is often accompanied by the other clinical features of infec- requires urgent antibiotic therapy, [], but at present, the tious mononucleosis (eg, generalized lymphadenopathy and evidence for F. necrophorum as a primary pathogen in acute splenomegaly). Systemic infections with cytomegalovirus, pharyngitis in adolescents and young adults is only suggestive.
rubella virus, measles virus, and a number of other viral Further study is required to determine the role of F. necropho- agents may be associated with acute pharyngitis. Human rum in acute pharyngitis, as well as the necessity for and effec- metapneumovirus and human bocavirus may cause lower IDSA Guideline for GAS Pharyngitis • CID • 7 As is evident from this list of potential etiologic agents, directly from throat swabs, with shorter turnaround time.
GAS pharyngitis is the only commonly occurring form of Rapid identification and treatment of patients with GAS phar- acute pharyngitis for which antibiotic therapy is definitely in- yngitis can reduce the risk of spread, allowing the patient to dicated. Therefore, for a patient with acute pharyngitis, the return to school or work sooner, and can reduce the acute as- clinical decision that usually needs to be made is whether or sociated morbidity , ]. The use of RADTs for certain not the pharyngitis is attributable to GAS.
populations (eg, patients in emergency departments) was re-ported to significantly increase the number of patients appro- priately treated for streptococcal pharyngitis, compared with blood agar plate has been the standard for the documentation RADTs currently available are highly specific (approximately of the presence of GAS pharyngitis in the upper respiratory 95%) when compared with blood agar plate cultures , , tract and for the confirmation of the clinical diagnosis of acute False-positive test results are highly unusual, and therefore thera- streptococcal pharyngitis , If performed correctly, peutic decisions can be made with confidence on the basis of a culture of a single throat swab on a blood agar plate is 90%– positive test result Unfortunately, the sensitivity of most 95% sensitive for detection of GAS pharyngitis [].
of these tests is 70%–90%, compared with blood agar plate Several variables affect the accuracy of throat culture results.
For example, the manner in which the swab is obtained has The first RADTs used latex agglutination methods, were rel- an important impact on the yield of streptococci atively insensitive, and had unclear end points. Newer tests Throat swab specimens should be obtained from the surface based on enzyme immunoassay techniques offer increased of either tonsils (or tonsillar fossae) and the posterior pharyn- sensitivity and a more sharply defined end point [, ].
geal wall. Other areas of the oral pharynx and mouth are not More recently, RADTs that use chemiluminescent DNA acceptable sites. Healthcare professionals who try to obtain a probes or optical immunoassay have been developed; however, throat swab from an uncooperative child without immobiliz- optical immunoassays are no longer commercially available. A ing the neck may obtain a specimen that is neither adequate variety of RADTs are available, and they are not all equal in nor representative. In addition, false-negative results may be their performance characteristics [].
obtained if the patient has received an antibiotic shortly The practitioner should be aware that, for some of these tests, the Clinical Laboratory Improvement Act of 1988 does not The use of anaerobic incubation and selective culture media waive the need for certification; use of nonwaived tests requires may increase the proportion of positive culture results proper certification of the physician’s laboratory. Neither but there are conflicting data in this regard. The increased cost conventional throat culture nor RADTs accurately differentiate and effort associated with anaerobic incubation and selective acutely infected persons from asymptomatic streptococcal carri- culture media are difficult to justify, particularly for physicians ers with intercurrent viral pharyngitis. Nevertheless, they allow who process throat cultures in their own offices.
physicians to withhold antibiotics from the great majority of pa- Another variable that can affect the throat culture result is tients with sore throats for whom results of culture or RADT the duration of incubation. Once plated, a culture should be are negative. This is of extreme importance, because nationally incubated at 35°C–37°C for 18–24 hours before reading. Addi- up to 70% of patients with sore throats seen in primary care tional incubation overnight at room temperature may identify settings receive prescriptions for antimicrobials [while only a number of additional positive throat culture results. Thus, 20%–30% are likely to have GAS pharyngitis [, although initial therapeutic decisions may be made on the Both RADTs and throat cultures may be affected by spec- basis of overnight culture, it is advisable to reexamine plates at trum bias. This refers to the phenomenon that, with a greater 48 hours that yield negative results at 24 hours [ pretest probability of GAS pharyngitis, the sensitivities of The clinical significance of the number of GAS colonies on RADTs and throat culture are greater []. Because the sensi- the throat culture plate is problematic. Although patients with tivities of the various RADTs are <90% in most studied popu- true acute GAS pharyngitis are likely to have more strongly lations of children and adolescents [and because positive cultures than patients who are streptococcal carriers the proportion of acute pharyngitis due to GAS in children (ie, individuals with chronic GAS colonization of the and adolescents is sufficiently high (20%–30%), a negative pharynx), there is too much overlap in this regard to permit RADT should be accompanied by a follow-up or back-up accurate differentiation on this basis alone ].
throat culture in children and adolescents, while this is not A major disadvantage of throat cultures is the necessary in adults under usual circumstances, as noted above.
delay (overnight or longer) in obtaining results. RADTs have Measurement of anti-streptococcal antibody titers is often been developed for the identification of GAS pharyngitis useful for diagnosis of the nonsuppurative sequelae of GAS pharyngitis, such as acute rheumatic fever and acute glomeru- performed on selected patients with clinical symptoms and lonephritis []. However, such testing is not useful in the di- signs on physical examination that are suggestive of GAS.
agnosis of acute pharyngitis because antibody titers of the 2 While treatment early in the course leads to a more rapid most commonly used tests, antistreptolysin O (ASO) and anti- clinical cure in patients with acute GAS pharyngitis and de- DNase B, may not reach maximum levels until 3–8 weeks creases transmission of GAS to other children, the predomi- after acute GAS pharyngeal infection and may remain elevated nant rationale for treatment of this self-limited illness is to for months even without active GAS infection , prevent suppurative and nonsuppurative complications [].
In particular, treatment within 9 days of the onset of illness iseffective in preventing acute rheumatic fever (ARF) [].
II. Who Should Undergo Testing for Group A Streptococcal However, treatment of pharyngitis does not affect the develop- ment of poststreptococcal glomerulonephritis Testing for GAS usually is not recommended for chil- Special Considerations in the Diagnosis of Acute Pharyn- dren or adults with acute pharyngitis with clinical and epide- GAS causes only 5%–15% of cases of acute miological features that strongly suggest a viral etiology (eg, pharyngitis in adults []. However, the risk of acute cough, rhinorrhea, hoarseness, and oral ulcers; strong, high).
pharyngitis due to GAS among adults is higher for parents of Diagnostic studies for GAS are not indicated for children school-age children and for those whose occupation brings <3 years old because acute rheumatic fever is rare in children them into close association with children. The risk of a first <3 years old and the incidence of streptococcal pharyngitis attack of ARF is extremely low in adults, even with an undiag- and the classic presentation of streptococcal pharyngitis are nosed and untreated episode of streptococcal pharyngitis.
uncommon in this age group. Selected children <3 years old Because of these epidemiological distinctions, the use of a who have other risk factors, such as an older sibling with GAS clinical algorithm without microbiological confirmation has infection, may be considered for testing (strong, moderate).
been suggested as an acceptable alternative basis for diagnosisof infection in adults ]. In emergency department prac- tice, a 4-factor algorithm predicted a positive result of GAS GAS as a cause of pharyngitis is most commonly observed in throat culture with an accuracy of 32%–56%, depending on children 5–15 years of age in winter and early spring in tem- the number of required clinical features present [].
perate climates (ie, November–May), with characteristics as However, use of this diagnostic strategy would result in treat- noted above (see special considerations in the diagnosis of ment of an unacceptably large number of adults with non- acute pharyngitis in adults section below). Many studies have streptococcal pharyngitis; that is an undesirable result in this shown that clinical scoring systems can be useful in predicting age group, which has a low prevalence of GAS pharyngitis the likelihood of streptococcal infection [, , ] but and a very low risk of rheumatic fever or rheumatic carditis.
that laboratory confirmation is essential in making a precise However, because of the above noted features of acute pharyn- diagnosis because physicians often greatly overestimate the gitis in adults, exclusion of the diagnosis on the basis of nega- probability that GAS is the cause of pharyngitis [A test tive RADT results without confirmation by negative culture negative for GAS provides reassurance that the patient likely results is an acceptable alternative to diagnosis on the basis of has a viral cause of pharyngitis. A negative test result also throat culture results The generally high specificity of allows the clinician to safely avoid the use of antibiotics. Selec- RADT should minimize overprescription of antimicrobials for tive use of diagnostic studies for GAS on the basis of clinical treatment of adults. This latter point is of particular impor- features increases not only the proportion of positive test tance in view of national data indicating that antibiotics— results but also the proportion of patients who have positive frequently, the more expensive, broader-spectrum antibiotics— test results and who are truly infected rather than mere carri- are prescribed for approximately three-quarters of adults who consult community primary care physicians because of a sore Because of the general increase in rates of resistance to anti- throat []. Physicians who wish to ensure they are achieving biotics, antimicrobial therapy should be prescribed only for maximal sensitivity in diagnosis may continue to use conven- proven episodes of GAS pharyngitis [, , The vast tional throat culture or to back up negative RADT results with majority of children and adults with acute pharyngitis have a viral etiology and do not need antibiotic treatment, even Children <3 Years Old With Pharyngitis.
during peak months. Additionally, many experts support the noted that GAS infection in children <3 years old is often as- idea of being selective about which children should have a di- sociated with fever, mucopurulent rhinitis, excoriated nares, agnostic throat culture performed, to avoid identifying carriers and diffuse adenopathy and that exudative pharyngitis is rare rather than acutely infected youngsters. GAS testing should be IDSA Guideline for GAS Pharyngitis • CID • 9 A recent meta-analysis estimated higher prevalence rates of without treatment, fever and symptoms commonly resolve GAS pharyngitis among school-age children (37%) compared within a few days of the onset of illness ]. The persistence to children <5 years. (24%) providing support for of symptoms beyond that period suggests either the develop- routine diagnostic tests in this age group. However, the preva- ment of a suppurative complication or that the child may be a lence of GAS pharyngitis is significantly lower for children <3 chronic carrier of GAS (rather than acutely infected) with an years of age, ranging from 10% to 14%, and if a corresponding intercurrent community-acquired viral pharyngitis (see question rise in ASO is required, the prevalence can be as low as 0%– V about streptococcal carriers). Therefore, follow-up cultures 6% [Thus, diagnostic testing for GAS pharyngitis is are not routinely recommended. Follow-up testing after a not routinely indicated in children <3 years of age.
course of treatment with an appropriate antibiotic should be One of the main indications for prompt testing and treat- reserved for those patients who are at particularly high risk of ment of GAS pharyngitis is the prevention of ARF. Reports of ARF or who have recurrence of classic symptoms compatible ARF in children <3 years of age are very rare [, ]. Of with GAS pharyngitis, as described previously.
541 new cases of ARF reported from Salt Lake City, Utah, Despite the universal susceptibility of GAS to penicillin, only 5% involved individuals <5 years of age. For those pa- 7%–37% of children treated with an appropriate antibiotic for tients, the median age was 4 years [In countries where apparent streptococcal pharyngitis have a throat culture posi- ARF is more common than in the United States, the rate tive for GAS at the end of therapy ]. These children are among young children is also low , ]. This is thought considered bacteriologic failures. Under most circumstances, to be because it may take repeated exposures to GAS or these children are actually streptococcal carriers, and further priming of the immune system before there is an immune re- antimicrobial therapy is not indicated (see question V about sponse to streptococcal pharyngitis that can lead to rheumatic fever []. The low prevalence of GAS pharyngitis and the lowrisk of developing ARF in children <3 years of age limits the usefulness of diagnostic testing in this age group.
Asymptomatic carriage of GAS has been frequently noted among However, if a child is <3 years of age and there is household household contacts of patients with GAS pharyngitis contact with a school-aged sibling with documented strepto- Up to one-third of households include individual(s) who will coccal pharyngitis, then it is reasonable to consider testing the develop symptomatic GAS pharyngitis that warrants diagnostic child if the child is symptomatic. Previous family studies dem- testing and treatment . In studies examining the role of anti- onstrate a high rate of secondary streptococcal infections biotic prophylaxis of household contacts of patients with GAS among household contacts. The likelihood of the spread of in- pharyngitis, penicillin prophylaxis has not been shown to reduce fection in a family is as high as 25% if the index subject has the incidence of subsequent GAS pharyngitis [al- symptomatic pharyngitis [, and studies demonstrate that though a small, statistically significant effect on secondary illness up to one-third of persons in a semiclosed community devel- has been shown for cephalosporin prophylaxis Antibiotic oped symptomatic pharyngitis during an outbreak use has been associated with adverse side effects such as rash, Therefore, if a child is in day care or another setting with a diarrhea, and, rarely, anaphylaxis, and unnecessary use of broad- high rate of cases of GAS infections, then it is reasonable to spectrum antibiotics leads to concerns about the potential spread test symptomatic children and treat them if they are found to of antibiotic-resistant organisms in the population. Given the self-limited nature of GAS pharyngitis, high frequency of GASthroat carriage, limited efficacy of antibiotic prophylaxis, and po-tential concerns about the direct and indirect risks associated with antibiotic use, routine testing or treatment of asymptomatic Follow-up posttreatment throat cultures or RADT are household contacts of patients with GAS pharyngitis is not not recommended routinely, but may be considered in special Diagnostic testing or empiric treatment of asymptomatic household contacts of patients with acute streptococcal phar- yngitis is not routinely recommended (strong, moderate).
III. What Are the Treatment Recommendations for Patients When a patient is prescribed an antibiotic for treatment of streptococcal pharyngitis, a clinical response is usually achieved within 24–48 hours of therapy. It is important to note that Patients with acute GAS pharyngitis should be treated streptococcal pharyngitis is usually a self-limited disease. Even with an appropriate antibiotic at an appropriate dose for a duration likely to eradicate the organism from the pharynx therapy is preferred for patients deemed unlikely to complete (usually 10 days). Based on their narrow spectrum of activity, a full 10-day course of oral therapy.
infrequency of adverse reactions, and modest cost, penicillin Certain antimicrobials are not recommended for treatment or amoxicillin is the recommended drug of choice for those of GAS pharyngitis. Tetracyclines should not be used because non-allergic to these agents (strong, high).
of the high prevalence of resistant strains. Sulfonamides and Treatment of GAS pharyngitis in penicillin-allergic indi- trimethoprim-sulfamethoxazole should not be used because viduals may include a first generation cephalosporin (for those they do not eradicate GAS from patients with acute pharyngi- not anaphylactically sensitive) for 10 days, clindamycin or tis Older fluoroquinolones (eg, ciprofloxacin) have clarithromycin for 10 days, or azithromycin for 5 days (strong, limited activity against GAS pharyngitis and should not be used to treat GAS pharyngitis [Newer fluoroquinolones(eg, levofloxacin and moxifloxacin) are active in vitro against GAS, but they are expensive and have an unnecessarily broad When selecting an antimicrobial for treatment of GAS pharyn- spectrum of activity and are therefore not recommended for gitis, important issues to consider include efficacy, safety, anti- microbial spectrum (narrow vs broad), dosing schedule, A 10-day course of an oral cephalosporin is recommended compliance with therapy (ie, adherence), and cost. These for most penicillin-allergic individuals (Table Narrow-spec- factors influence the cost-effectiveness of antimicrobial therapy.
trum cephalosporins, such as cefadroxil or cephalexin, are A number of antibiotics have been shown to be effective in much preferred to broad-spectrum cephalosporins, such as ce- treating GAS pharyngitis (Table ). These include penicillin faclor, cefuroxime, cefixime, cefdinir, and cefpodoxime. Most and its congeners (eg, ampicillin and amoxicillin), as well as oral broad-spectrum cephalosporins are considerably more ex- numerous cephalosporins, macrolides, and clindamycin. Peni- pensive than penicillin or amoxicillin, and the former agents cillin, however, remains the treatment of choice because of its are more likely to select for antibiotic-resistant flora [].
proven efficacy and safety, its narrow spectrum, and its low Some penicillin-allergic persons (up to 10%) are also allergic cost , Penicillin-resistant GAS has never been to cephalosporins, and these agents should not be used in documented. Amoxicillin is often used in place of penicillin V patients with immediate (anaphylactic-type) hypersensitivity to as oral therapy for young children; the efficacy appears to be equal. This choice is primarily related to acceptance of the Clindamycin resistance among GAS isolates in the United States is approximately 1%, and this is a reasonable agent for In comparative clinical trials, once-daily amoxicillin (50 treating penicillin-allergic patients [].
mg/kg, to a maximum of 1000 mg) for 10 days has been An oral macrolide (erythromycin or clarithromycin) or shown to be effective for GAS pharyngitis [This some- azalide (azithromycin at a dose of 12 mg/kg/day, up to a what broader-spectrum agent has the advantage of once-daily maximum of 500 mg) is also reasonable for patients allergic to dosing, which may enhance adherence, and is relatively inex- penicillin. Ten days of therapy is indicated for all but azithro- mycin, which is given for 5 days. Erythromycin is associated Most oral antibiotics must be administered for the conven- with substantially higher rates of gastrointestinal side effects tional 10 days to achieve maximal rates of pharyngeal eradica- than the other agents. Strains of GAS resistant to these agents tion of GAS. Currently, the US Food and Drug Administration have been highly prevalent in some areas of the world and has approved cefdinir cefpodoxime , ], and have resulted in treatment failures In recent years, mac- azithromycin [] for a 5-day course of therapy for GAS phar- rolide resistance rates among pharyngeal isolates in most areas yngitis. However, many studies of short-course cephalosporin of the United States have been around 5%–8% One therapy lack strict entry criteria, include no assessment of com- study suggests that 10 days of clarithromycin may be more ef- pliance with therapy, and do not include serotypic or genotypic fective in eradicating GAS pharyngitis than 5 days of azithro- differentiation between infections for which treatment failed and newly acquired infections. In addition, the spectra of theseantibiotics are much broader than the spectrum of penicillin, USE OF ADJUNCTIVE THERAPEUTICS FOR STREP THROAT and, even when the antibiotics are administered for short IV. Should Adjunctive Therapy With NSAIDs, Acetaminophen, courses, they are more expensive []. Therefore, use of these Aspirin, or Corticosteroids Be Given to Patients Diagnosed With shorter courses of oral cephalosporins cannot be endorsed at Antimicrobials for GAS pharyngitis may be given either Adjunctive therapy is often useful in the management orally or parenterally. Intramuscular benzathine penicillin G IDSA Guideline for GAS Pharyngitis • CID • 11 If warranted, use of an analgesic/antipyretic agent such as V. Is the Patient With Frequent Recurrent Episodes of Apparent acetaminophen or an NSAID for treatment of moderate to GAS Pharyngitis Likely to Be a Chronic Pharyngeal Carrier of severe symptoms or control of high fever associated with GAS pharyngitis should be considered as an adjunct to an appro- We recommend that clinicians caring for patients with Aspirin should be avoided in children (strong, moderate).
recurrent episodes of pharyngitis associated with laboratory Adjunctive therapy with a corticosteroid is not recom- evidence of GAS consider that they may be experiencing >1 episode of bona fide streptococcal pharyngitis at close inter-vals, but they should also be alert to the possibility that the patient may actually be a chronic pharyngeal GAS carrier who Multiple studies, including randomized, double-blind, and is experiencing repeated viral infections (strong, moderate).
placebo-controlled studies, support the benefits of NSAIDs We recommend that GAS carriers do not ordinarily such as ibuprofen in reducing fever and pain relative to placebo justify efforts to identify them nor do they generally require among both children and adults with pharyngitis. No signifi- antimicrobial therapy because GAS carriers are unlikely to cant adverse events were noted. In other randomized, double- spread GAS pharyngitis to their close contacts and are at little blind, and placebo-controlled studies, significantly greater pain or no risk for developing suppurative or nonsuppurative com- relief with use of acetaminophen compared with placebo has plications (eg, acute rheumatic fever; strong, moderate).
been documented among both children and adults, although We do not recommend tonsillectomy solely to reduce improvement in symptoms was not always equivalent to that the frequency of GAS pharyngitis (strong, high).
Although aspirin has also been shown to reduce pain in adults with upper respiratory tract infection, we recommend against the use of aspirin for pain relief of pharyngitis in chil- Because routine posttherapy retesting is no longer advised for dren because of the risk of Reye syndrome.
patients with acute GAS pharyngitis, only those with recurrent Results from randomized, double-blind, placebo-controlled signs and symptoms of acute pharyngitis within weeks or studies demonstrate that corticosteroids decrease the duration months of completing therapy for an acute pharyngitis are and severity of signs and symptoms in GAS pharyngitis in likely to seek reassessment. If such symptomatic patients again adults and children, although the actual decrease in pain dura- have positive culture and/or RADT results, there are several tion is minimal (approximately 5 hours) It is diffi- possible explanations: noncompliance with the prescribed an- cult to compare the magnitude of the effect across the various tibiotics; a new GAS pharyngeal infection acquired from studies because of differences in the agent selected, route, and family contacts, classroom contacts, or other community con- dosage used; method of assessing pain; time of follow-up; and tacts; or chronic GAS carriage with intercurrent viral infec- limitations of follow-up by telephone The effect of con- tions A second episode of pharyngitis caused by comitant administration of NSAIDs and acetaminophen in the original infecting strain of GAS cannot be ruled out but is these patients is unclear. Although adverse effects of the therapy were not evident in the published data, long-term Chronic pharyngeal carriers have GAS present in the follow-up had not been done. Given the efficacy of antimicro- pharynx but have no evidence of an active immunologic re- bials, the self-limited nature of GAS pharyngitis, the efficacy sponse to the organism, such as rising anti-streptococcal anti- of systemic and some topical analgesics in decreasing the body titers [, During the winter and spring in acute symptoms of GAS pharyngitis, and the potential of temperate climates, as many as 20% of asymptomatic school- adverse effects of systemic steroids, we do not recommend use age children may be GAS carriers. They may be colonized by of corticosteroids in therapy of this illness.
GAS pharyngitis for ≥6 months and during that time may ex- A variety of topical agents have been marketed for therapy of perience episodes of intercurrent viral pharyngitis [, ].
acute pharyngitis. These include rinses, sprays, and lozenges.
Testing of such patients often demonstrates evidence of GAS Several contain topical anesthetics, such as ambroxol, lidocaine, in the pharynx, and thus they may mimic patients with acute and benzocaine, that may give temporary symptomatic relief.
streptococcal pharyngitis. Individuals who are identified as Lozenges may be effective but represent a choking hazard for chronic pharyngeal GAS carriers do not ordinarily require young children [Topical agents for pharyngitis in both further antimicrobial therapy. Carriers appear to be unlikely children and adults have recently been reviewed ]. A to spread the organism to their close contacts and are thought remedy commonly used in patients old enough to gargle— to be at very low risk, if any, for developing suppurative or warm salt water rinses—has not been studied in detail.
invasive complications or nonsuppurative complications (eg, Treatment Regimens for Chronic Carriers of Group A Streptococci 20–30 mg/kg/d in 3 doses (max = 300 mg/dose) Penicillin V: 50 mg/kg/d in 4 doses × 10 d (max = 2000 mg/d); rifampin: 20 mg/kg/din 1 dose × last 4 d of treatment(max = 600 mg/d) 40 mg amoxicillin/kg/d in 3 doses (max = 2000 Benzathine penicillin G: 600 000 U for <27 kg and 1 200 000 U for ≥27 kg; rifampin: 20 mg/ acute rheumatic fever) [, , Additionally, it is much single episode of pharyngitis associated with laboratory confir- more difficult to eradicate GAS pharyngitis from the throats mation of GAS that occurs shortly after completion of a of carriers than from patients with bona fide acute streptococ- course of appropriate antimicrobial therapy, treatment with cal infections , ]. This is particularly true for peni- any of the agents listed in Table is appropriate. Since patient cillin or amoxicillin therapy and may also be true for some adherence to oral antimicrobial therapy often is an issue, in- other antimicrobials [, , Clinical and epidemiolog- tramuscular benzathine penicillin G should be considered. For ical evidence suggests that, in published studies showing peni- these individual second episodes, it is not necessary to obtain cillin or amoxicillin to have relatively high failure rates for additional throat swab specimens for culture after the second eradicating GAS pharyngitis, the patient population was likely course of therapy unless the patient remains or becomes “contaminated” with chronic carriers symptomatic or unless one of the special circumstances noted Antimicrobial therapy is not indicated for the large majority of chronic streptococcal carriers. However, there are special An even more challenging clinical circumstance is the situations in which eradication of carriage may be desirable, person (usually a school-aged child or adolescent) who, within including the following: (1) during a community outbreak of a period of months to years, experiences multiple episodes of acute rheumatic fever, acute poststreptococcal glomerulone- acute pharyngitis for which culture and/or RADT results iden- phritis, or invasive GAS infection; (2) during an outbreak of tify GAS. It is likely that most of these patients are chronic GAS pharyngitis in a closed or partially closed community; streptococcal carriers who are experiencing repeated viral in- (3) in the presence of a family or personal history of acute fections. For patients with frequent discrete episodes, informa- rheumatic fever; (4) in a family with excessive anxiety about tion regarding the precise nature of the presenting signs and GAS infections; or (5) when tonsillectomy is being considered symptoms (Table ), the clinical response to antibiotic only because of carriage. A number of antimicrobial schedules therapy, and the presence or absence of GAS pharyngitis in have been demonstrated to be substantially more effective cultures of throat swabs obtained during asymptomatic inter- than penicillin or amoxicillin in eliminating chronic strepto- vals is helpful in distinguishing persistent carriage from recur- rent episodes of acute GAS pharyngitis. Serotyping or In routine practice, it is often difficult to differentiate a GAS genotyping of streptococcal isolates recovered from specimens carrier with an intercurrent viral infection from a patient with obtained during distinct episodes from an individual patient acute streptococcal pharyngitis. Helpful clues include patient may also assist in arriving at this determination because a age, season, local epidemiological characteristics (eg, the local carrier has persistence of the same strain of GAS over prevalence of influenza and/or enteroviral illnesses), and the time. Unfortunately, such studies are available only from spe- precise nature of the presenting signs and symptoms (Table cialized research laboratories and are unlikely to be available In many instances, however, the clinician may not be able within a practical time frame. There have been no definitive to distinguish persistent carriage from acute infection and will controlled studies of treatment of multiple repeated sympto- elect to administer another course of antimicrobials. For a matic episodes of culture-positive acute pharyngitis in the IDSA Guideline for GAS Pharyngitis • CID • 13 same person. However, the regimens listed in Table have 2. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging con- been reported to result in low rates of bacteriologic failure sensus on rating quality of evidence and strength of recommenda-tions. BMJ 2008; 336:924–6.
Continuous antimicrobial prophylaxis is not recom- 3. Guyatt GH, Oxman AD, Kunz R, et al. Going from evidence to rec- mended except to prevent recurrent ARF in patients who have ommendations. BMJ 2008; 336:1049–51.
experienced a previous episode of rheumatic fever.
4. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schune- mann HJ. What is “quality of evidence” and why is it important to If a physician suspects that “ping-pong” spread of infections is the explanation for multiple recurrent episodes of infections 5. Jaeschke R, Guyatt GH, Dellinger P, et al. Use of GRADE grid to within a family, it may be helpful to obtain throat swabs from reach decisions on clinical practice guidelines when consensus iselusive. BMJ 2008; 337:a744.
all family contacts simultaneously and to treat those for whom 6. Schunemann HJ, Oxman AD, Brozek J, et al. Grading quality of evi- culture or RADT results are positive. There is no credible evi- dence and strength of recommendations for diagnostic tests and dence that family pets are reservoirs for GAS pharyngitis or strategies. BMJ 2008; 336:1106–10.
that they contribute to familial spread.
7. Kish MA. Guide to development of practice guidelines. Clin Infect Tonsillectomy may be considered in the rare patient whose 8. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice symptomatic episodes do not diminish in frequency over time guideline for acute bacterial rhinosinusitis in children and adults.
and for whom no alternative explanation for recurrent GAS 9. Bisno AL. Acute pharyngitis: etiology and diagnosis. Pediatrics 1996; pharyngitis is evident. However, tonsillectomy has been dem- onstrated to be beneficial only for a relatively small group of 10. Ebell MH, Smith MA, Barry HC, Ives K, Carey M. The rational clin- these patients, and any benefit can be expected to be relatively ical examination. Does this patient have strep throat? JAMA 2000;284:2912–8.
11. Lindbaek M, Francis N, Cannings-John R, Butler CC, Hjortdahl P.
Clinical course of suspected viral sore throat in young adults: cohort study. Scand J Prim Health Care 2006; 24:93–7.
12. Wannamaker LW. Perplexity and precision in the diagnosis of strep- tococcal pharyngitis. Am J Dis Child 1972; 124:352–8.
Future research should focus on the following: (1) improved 13. Linder JA, Bates DW, Lee GM, Finkelstein JA. Antibiotic treatment rapid methods for diagnosis of acute GAS pharyngitis and for of children with sore throat. JAMA 2005; 294:2315–22.
14. Linder JA, Chan JC, Bates DW. Evaluation and treatment of pharyn- distinguishing acute infection from chronic pharyngeal car- gitis in primary care practice: the difference between guidelines is riage, (2) development of simpler or shorter therapeutic regi- largely academic. Arch Intern Med 2006; 166:1374–9.
mens for acute GAS pharyngitis, and (3) development of an 15. McCaig LF, Besser RE, Hughes JM. Trends in antimicrobial prescrib- affordable, safe, and effective GAS vaccine against the broad ing rates for children and adolescents. JAMA 2002; 287:3096–102.
16. Pfoh E, Wessels MR, Goldmann D, Lee GM. Burden and economic cost of group A streptococcal pharyngitis. Pediatrics 2008; 121:229–34.
17. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group a streptococcal diseases. Lancet Infect Dis 2005;5:685–94.
The Panel thanks Drs Robert Baltimore, Georges 18. Field MJL, Kathleen N. Institute of Medicine Committee to Advise Peter, and Michael Wessels, for their thoughtful reviews of the guideline; the Public Health Service on Clinical Practice Guidelines. Clinical and Jennifer Padberg and Vita Washington, for their overall guidance in practice guidelines: directions for a new program. Washington, DC: all aspects of the development of the guideline.
National Academy Press, 1990:52–77.
This work was supported by the Infectious Diseases 19. Breese BB. A simple scorecard for the tentative diagnosis of strepto- coccal pharyngitis. Am J Dis Child 1977; 131:514–7.
Potential conflicts of Interest. The following list is a reflection of what 20. McIsaac WJ, Kellner JD, Aufricht P, Vanjaka A, Low DE. Empirical has been reported to the IDSA. To provide thorough transparency, the validation of guidelines for the management of pharyngitis in chil- IDSA requires full disclosure of all relationships, regardless of relevancy to dren and adults. JAMA 2004; 291:1587–95.
the guideline topic. The reader of these guidelines should be mindful of 21. Poses RM, Cebul RD, Collins M, Fager SS. The accuracy of experi- this when the list of disclosures is reviewed. S. S. has served as a consultant enced physicians’ probability estimates for patients with sore throats.
to Novartis Vaccines and Merck Vaccines and received research support implications for decision making. JAMA 1985; 254:925–9.
from Quidel. A. B. has served as a consultant for SPD Development, Cor- 22. Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The nerstone BioPharma, and Rib-X Pharmaceuticals. All other authors report diagnosis of strep throat in adults in the emergency room. Med All authors have submitted the ICMJE Form for Disclosure of Potential 23. Kaplan EL, Top FH Jr, Dudding BA, Wannamaker LW. Diagnosis of Conflicts of Interest. Conflicts that the editors consider relevant to the streptococcal pharyngitis: differentiation of active infection from the content of the manuscript have been disclosed.
carrier state in the symptomatic child. J Infect Dis 1971; 123:490–501.
24. Hustedt JW, Vazquez M. The changing face of pediatric respiratory tract infections: how human metapneumovirus and human bocavirusfit into the overall etiology of respiratory tract infections in young 1. Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH.
children. Yale J Biol Med 2010; 83:193–200.
Practice guidelines for the diagnosis and management of group a 25. Mackenzie A, Fuite LA, Chan FT, et al. Incidence and pathogenicity streptococcal pharyngitis. Infectious Diseases Society of America.
of Arcanobacterium haemolyticum during a 2-year study in Ottawa.
26. Nyman M, Alugupalli KR, Stromberg S, Forsgren A. Antibody re- primary care physician. Pediatr Infect Dis J 2002; 21:420–6; quiz sponse to Arcanobacterium haemolyticum infection in humans. J 48. Johnson DR, Kurlan R, Leckman J, Kaplan EL. The human immune 27. Cimolai N, Elford RW, Bryan L, Anand C, Berger P. Do the beta- response to streptococcal extracellular antigens: clinical, diagnostic, and hemolytic non-group A streptococci cause pharyngitis? Rev Infect potential pathogenetic implications. Clin Infect Dis 2010; 50:481–90.
49. Wald ER, Green MD, Schwartz B, Barbadora K. A streptococcal 28. Turner JC, Hayden FG, Lobo MC, Ramirez CE, Murren D. Epidemi- score card revisited. Pediatr Emerg Care 1998; 14:109–11.
ologic evidence for Lancefield group C beta-hemolytic streptococci 50. Kaplan EL. The group A streptococcal upper respiratory tract carrier as a cause of exudative pharyngitis in college students. J Clin Micro- state: an enigma. J Pediatr 1980; 97:337–45.
51. Report of the Committee on Infectious Disease. Pickering LK, editor.
29. Meier FA, Centor RM, Graham L Jr, Dalton HP. Clinical and micro- 29th Edition, Group A Streptococcal Infections. Elk Grove Village, biological evidence for endemic pharyngitis among adults due to IL: American Academy of Pediatrics, 2012:668–80.
group C streptococci. Arch Intern Med 1990; 150:825–9.
52. Dajani A, Taubert K, Ferrieri P, Peter G, Shulman S. Treatment of 30. Gerber MA, Randolph MF, Martin NJ, et al. Community-wide out- acute streptococcal pharyngitis and prevention of rheumatic fever: a break of group G streptococcal pharyngitis. Pediatrics 1991; statement for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascu- 31. Amess JA, O’Neill W, Giollariabhaigh CN, Dytrych JK. A six-month lar Disease in the Young, the American Heart Association. Pediatrics audit of the isolation of Fusobacterium necrophorum from patients with sore throat in a district general hospital. Br J Biomed Sci 2007; 53. Wannamaker LW, Rammelkamp CH Jr, Denny FW, et al. Prophylax- is of acute rheumatic fever by treatment of the preceding streptococ- 32. Jensen A, Hagelskjaer Kristensen L, Prag J. Detection of Fusobacte- cal infection with various amounts of depot penicillin. Am J Med rium necrophorum subsp. funduliforme in tonsillitis in young adults by real-time PCR. Clin Microbiol Infect 2007; 13:695–701.
54. Rammelkamp CH Jr. Glomerulonephritis. Proc Inst Med Chic 1953; 33. Batty A, Wren MW, Gal M. Fusobacterium necrophorum as the cause of recurrent sore throat: comparison of isolates from persistent sore 55. Komaroff AL, Pass TM, Aronson MD, et al. The prediction of throat syndrome and Lemierre’s disease. J Infect 2005; 51:299–306.
streptococcal pharyngitis in adults. J Gen Intern Med 1986; 1:1–7.
34. Centor RM, Geiger P, Waites KB. Fusobacterium necrophorum bac- 56. Bisno AL. Acute pharyngitis. N Engl J Med 2001; 344:205–11.
teremic tonsillitis: 2 cases and a review of the literature. Anaerobe 57. Cooper RJ, Hoffman JR, Bartlett JG, et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann 35. Riordan T. Human infection with Fusobacterium necrophorum (Nec- robacillosis), with a focus on Lemierre’s syndrome. Clin Microbiol 58. Humair JP, Revaz SA, Bovier P, Stalder H. Management of acute pharyngitis in adults: reliability of rapid streptococcal tests and clini- 36. Snow V, Mottur-Pilson C, Cooper RJ, Hoffman JR. Principles of ap- cal findings. Arch Intern Med 2006; 166:640–4.
propriate antibiotic use for acute pharyngitis in adults. Ann Intern 59. Boisvert PL, Darrow D, Powers GF, et al. Streptococci in children.
37. Gerber MA. Diagnosis of pharyngitis: methodology of throat cul- 60. Shaikh N, Leonard E, Martin JM. Prevalence of streptococcal phar- tures. In: Shulman ST, ed. Pharyngitis: management in an era of de- yngitis and streptococcal carriage in children: a meta-analysis. Pedi- clining rheumatic fever. New York: Praeger, 1984:61–72.
38. Gerber MA. Comparison of throat cultures and rapid strep tests for 61. Nussinovitch M, Finkelstein Y, Amir J, Varsano I. Group A beta-he- diagnosis of streptococcal pharyngitis. Pediatr Infect Dis J 1989; molytic streptococcal pharyngitis in preschool children aged 3 months to 5 years. Clin Pediatr (Phila) 1999; 38:357–60.
39. Schwartz RH, Gerber MA, McCoy P. Effect of atmosphere of incuba- 62. Amir J, Shechter Y, Eilam N, Varsano I. Group A beta-hemolytic tion on the isolation of group A streptococci from throat cultures. J streptococcal pharyngitis in children younger than 5 years. Isr J Med 40. Brien JH, Bass JW. Streptococcal pharyngitis: optimal site for throat 63. Rimoin AW, Hamza HS, Vince A, et al. Evaluation of the WHO clin- culture. J Pediatr 1985; 106:781–3.
ical decision rule for streptococcal pharyngitis. Arch Dis Child 2005; 41. Kellogg JA. Suitability of throat culture procedures for detection of group A streptococci and as reference standards for evaluation of 64. Tani LY, Veasy LG, Minich LL, Shaddy RE. Rheumatic fever in chil- streptococcal antigen detection kits. J Clin Microbiol 1990; 28:165–9.
dren younger than 5 years: is the presentation different? Pediatrics 42. Randolph MF, Gerber MA, DeMeo KK, Wright L. Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis. J Pediatr 65. Gordis L. The virtual disappearance of rheumatic fever in the United States: lessons in the rise and fall of disease. T. Duckett Jones Memo- 43. Gerber MA, Shulman ST. Rapid diagnosis of pharyngitis caused by rial Lecture. Circulation 1985; 72:1155–62.
group A streptococci. Clin Microbiol Rev 2004; 17:571–80.
66. Ramanan PV, Premkumar S, Ramnath B. Youngest patient with 44. Tanz RR, Gerber MA, Kabat W, Rippe J, Seshadri R, Shulman ST.
Sydenham’s chorea: a case report. J Indian Med Assoc 2009; 107:246, 53.
Performance of a rapid antigen-detection test and throat culture in 67. Vinker S, Zohar E, Hoffman R, Elhayany A. Incidence and clinical community pediatric offices: implications for management of phar- manifestations of rheumatic fever: a 6 year community-based survey.
yngitis. Pediatrics 2009; 123:437–44.
45. Johnson DR, Kaplan EL. False-positive rapid antigen detection test 68. Paulo LT, Terreri MT, Barbosa CM, Len CA, Hilario MO. [Is results: reduced specificity in the absence of group A streptococci in rheumatic fever a more severe disease in pre-school children?]. Acta the upper respiratory tract. J Infect Dis 2001; 183:1135–7.
46. Nyquist AC, Gonzales R, Steiner JF, Sande MA. Antibiotic prescrib- 69. Ramanan PV, Anand K. Post varicella thrombosis. Indian Pediatr ing for children with colds, upper respiratory tract infections, and 70. Ellis NM, Kurahara DK, Vohra H, et al. Priming the immune system 47. Shet A, Kaplan EL. Clinical use and interpretation of group a strep- for heart disease: a perspective on group A streptococci. J Infect Dis tococcal antibody tests: a practical approach for the pediatrician or IDSA Guideline for GAS Pharyngitis • CID • 15 71. James WE, Badger GF, Dingle JH. A study of illness in a group of 94. Tack KJ, Henry DC, Gooch WM, Brink DN, Keyserling CH. Five- Cleveland families. XIX. The epidemiology of the acquisition of day cefdinir treatment for streptococcal pharyngitis. Cefdinir Phar- group A streptococci and of associated illnesses. N Engl J Med 1960; 72. Gastanaduy AS, Kaplan EL, Huwe BB, McKay C, Wannamaker LW.
95. Pichichero ME, Gooch WM, Rodriguez W, et al. Effective short- Failure of penicillin to eradicate group A streptococci during an out- course treatment of acute group A beta-hemolytic streptococcal break of pharyngitis. Lancet 1980; 2:498–502.
tonsillopharyngitis. Ten days of penicillin V vs 5 days or 10 days of 73. Dingle JH, Badger G, Jordan WS Jr. Illness in the home. Cleveland: cefpodoxime therapy in children. Arch Pediatr Adolesc Med 1994; Case Western Reserve University Press, 1964:97–119.
74. Musher DM. How contagious are common respiratory tract infec- 96. Portier H, Chavanet P, Waldner-Combernoux A, et al. Five versus tions? N Engl J Med 2003; 348:1256–66.
ten days treatment of streptococcal pharyngotonsillitis: a randomized 75. Brink WR, Rammelkamp CH Jr, Denny FW, Wannamaker LW.
controlled trial comparing cefpodoxime proxetil and phenoxymethyl Effect in penicillin and aureomycin on the natural course of strepto- penicillin. Scand J Infect Dis 1994; 26:59–66.
coccal tonsillitis and pharyngitis. Am J Med 1951; 10:300–8.
97. Hooton TM. A comparison of azithromycin and penicillin V for the 76. Zwart S, Rovers MM, de Melker RA, Hoes AW. Penicillin for acute treatment of streptococcal pharyngitis. Am J Med 1991; 91:23S–6S.
sore throat in children: randomised, double blind trial. BMJ 2003; 98. Gerber MA. Antibiotic resistance in group A streptococci. Pediatr 77. Middleton DB, D’Amico F, Merenstein JH. Standardized sympto- 99. Coonan KM, Kaplan EL. In vitro susceptibility of recent North matic treatment versus penicillin as initial therapy for streptococcal American group A streptococcal isolates to eleven oral antibiotics.
pharyngitis. J Pediatr 1988; 113:1089–94.
Pediatr Infect Dis J 1994; 13:630–5.
78. Peter G, Smith AL. Group A streptococcal infections of the skin and 100. Wickman PA, Black JA, Moland ES, Thomson KS. In vitro activities pharynx (second of two parts). N Engl J Med 1977; 297:365–70.
of DX-619 and comparison quinolones against gram-positive cocci.
79. Peter G, Smith AL. Group A streptococcal infections of the skin and Antimicrob Agents Chemother 2006; 50:2255–7.
pharynx (first of two parts). N Engl J Med 1977; 297:311–7.
101. Wilcox MH. The tide of antimicrobial resistance and selection. Int J 80. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat.
Antimicrob Agents 2009; 34(Suppl 3):S6–10.
Cochrane Database Syst Rev 2006:CD000023.
102. Colodner R, Rock W, Chazan B, et al. Risk factors for the develop- 81. Tanz RR, Shulman ST, Barthel MJ, Willert C, Yogev R. Penicillin ment of extended-spectrum beta-lactamase-producing bacteria in plus rifampin eradicates pharyngeal carriage of group A streptococci.
nonhospitalized patients. Eur J Clin Microbiol Infect Dis 2004; 82. Kaplan EL, Gooch IW, Notario GF, Craft JC. Macrolide therapy of 103. Pichichero ME. A review of evidence supporting the American group A streptococcal pharyngitis: 10 days of macrolide therapy Academy of Pediatrics recommendation for prescribing cephalospo- (clarithromycin) is more effective in streptococcal eradication than 5 rin antibiotics for penicillin-allergic patients. Pediatrics 2005; days (azithromycin). Clin Infect Dis 2001; 32:1798–802.
83. Klein JO. Management of streptococcal pharyngitis. Pediatr Infect 104. Tanz RR, Shulman ST, Shortridge VD, et al. Community-based sur- veillance in the united states of macrolide-resistant pediatric pharyn- 84. Kikuta H, Shibata M, Nakata S, et al. Efficacy of antibiotic prophy- geal group A streptococci during 3 respiratory disease seasons. Clin laxis for intrafamilial transmission of group A beta-hemolytic strep- tococci. Pediatr Infect Dis J 2007; 26:139–41.
105. Seppala H, Nissinen A, Jarvinen H, et al. Resistance to erythromycin 85. El Kholy A, Fraser DW, Guirguis N, Wannamaker LW, Plikaytis BD, in group A streptococci. N Engl J Med 1992; 326:292–7.
Zimmerman RA. A controlled study of penicillin therapy of group A 106. Schachtel BP, Thoden WR. A placebo-controlled model for assaying streptococcal acquisitions in Egyptian families. J Infect Dis 1980; systemic analgesics in children. Clin Pharmacol Ther 1993; 53: 86. No authors listed. Rheumatic fever and rheumatic heart disease.
107. Gehanno P, Dreiser RL, Ionescu E, Gold M, Liu JM. Lowest effective Report of a WHO Study Group. World Health Organ Tech Rep Ser single dose of diclofenac for antipyretic and analgesic effects in acute febrile sore throat. Clin Drug Investig 2003; 23:263–71.
87. Shulman ST, Gerber MA, Tanz RR, Markowitz M. Streptococcal pharyn- 108. Bertin L, Pons G, d’Athis P, et al. Randomized, double-blind, multi- gitis: the case for penicillin therapy. Pediatr Infect Dis J 1994; 13:1–7.
center, controlled trial of ibuprofen versus acetaminophen ( paraceta- 88. Feder HM Jr, Gerber MA, Randolph MF, Stelmach PS, Kaplan EL.
mol) and placebo for treatment of symptoms of tonsillitis and Once-daily therapy for streptococcal pharyngitis with amoxicillin.
pharyngitis in children. J Pediatr 1991; 119:811–4.
109. McNally D, Simpson M, Morris C, Shephard A, Goulder M. Rapid 89. Gerber MA, Tanz RR. New approaches to the treatment of group A relief of acute sore throat with AMC/DCBA throat lozenges: rando- streptococcal pharyngitis. Curr Opin Pediatr 2001; 13:51–5.
mised controlled trial. Int J Clin Pract 2010; 64:194–207.
90. Clegg HW, Ryan AG, Dallas SD, et al. Treatment of streptococcal 110. Olympia RP, Khine H, Avner JR. Effectiveness of oral dexamethasone pharyngitis with once-daily compared with twice-daily amoxicillin: a in the treatment of moderate to severe pharyngitis in children. Arch noninferiority trial. Pediatr Infect Dis J 2006; 25:761–7.
Pediatr Adolesc Med 2005; 159:278–82.
91. Lennon DR, Farrell E, Martin DR, Stewart JM. Once-daily amoxicil- 111. Bulloch B, Kabani A, Tenenbein M. Oral dexamethasone for the lin versus twice-daily penicillin V in group A beta-haemolytic strep- treatment of pain in children with acute pharyngitis: a randomized, tococcal pharyngitis. Arch Dis Child 2008; 93:474–8.
double-blind, placebo-controlled trial. Ann Emerg Med 2003; 92. Shvartzman P, Tabenkin H, Rosentzwaig A, Dolginov F. Treatment of streptococcal pharyngitis with amoxycillin once a day. BMJ 1993; 112. Wing A, Villa-Roel C, Yeh B, Eskin B, Buckingham J, Rowe BH. Ef- fectiveness of corticosteroid treatment in acute pharyngitis: a system- 93. Tack KJ, Hedrick JA, Rothstein E, Nemeth MA, Keyserling C, Pichi- atic review of the literature. Acad Emerg Med 2010; 17:476–83.
chero ME. A study of 5-day cefdinir treatment for streptococcal 113. Thomas M, Del Mar C, Glasziou P. How effective are treatments pharyngitis in children. Cefdinir Pediatric Pharyngitis Study Group.
other than antibiotics for acute sore throat? Br J Gen Pract 2000; Arch Pediatr Adolesc Med 1997; 151:45–9.
114. Gerber MA, Tanz RR, Kabat W, et al. Potential mechanisms for 125. Bass JW, Person DA, Chan DS. Twice-daily oral penicillin for treat- failure to eradicate group A streptococci from the pharynx. Pediatrics ment of streptococcal pharyngitis: less is best. Pediatrics 2000; 115. Martin JM, Green M, Barbadora KA, Wald ER. Group A streptococci 126. Gerber MA, Spadaccini LJ, Wright LL, Deutsch L, Kaplan EL. Twice- among school-aged children: clinical characteristics and the carrier daily penicillin in the treatment of streptococcal pharyngitis. Am J state. Pediatrics 2004; 114:1212–9.
116. Kaplan EL, Gastanaduy AS, Huwe BB. The role of the carrier in 127. Bass JW, Crast FW, Knowles CR, Onufer CN. Streptococcal treatment failures after antibiotic for group A streptococci in the pharyngitis in children. A comparison of four treatment schedules upper respiratory tract. J Lab Clin Med 1981; 98:326–35.
117. Shulman ST. Streptococcal pharyngitis: diagnostic considerations.
Pediatr Infect Dis J 1994; 13:567–71.
128. Stillerman M, Isenberg HD. Streptococcal pharyngitis therapy: com- 118. Chaudhary S, Bilinsky SA, Hennessy JL, et al. Penicillin V and rifam- parison of cyclacillin, cephalexin, and potassium penicillin V. Anti- pin for the treatment of group A streptococcal pharyngitis: a random- microb Agents Chemother (Bethesda) 1970; 10:270–6.
ized trial of 10 days penicillin vs 10 days penicillin with rifampin 129. Stillerman M, Isenberg HD, Moody M. Streptococcal pharyngitis during the final 4 days of therapy. J Pediatr 1985; 106:481–6.
therapy. Comparison of cephalexin, phenoxymethyl penicillin, and 119. Tanz RR, Poncher JR, Corydon KE, Kabat K, Yogev R, Shulman ST.
ampicillin. Am J Dis Child 1972; 123:457–61.
Clindamycin treatment of chronic pharyngeal carriage of group A 130. Disney FA, Dillon H, Blumer JL, et al. Cephalexin and penicillin in streptococci. J Pediatr 1991; 119:123–8.
the treatment of group A beta-hemolytic streptococcal throat infec- 120. Kaplan EL, Johnson DR. Eradication of group A streptococci from tions. Am J Dis Child 1992; 146:1324–7.
the upper respiratory tract by amoxicillin with clavulanate after oral 131. Disney FA, Breese BB, Green JL, Talpey WB, Tobin JR. Cephalexin penicillin V treatment failure. J Pediatr 1988; 113:400–3.
and penicillin therapy of childhood beta-hemolytic streptococcal in- 121. Paradise JL, Bluestone CD, Bachman RZ, et al. Efficacy of tonsillecto- fections. Postgrad Med J 1971; 47(Suppl):47–51.
my for recurrent throat infection in severely affected children.
132. Gerber MA, Randolph MF, Chanatry J, Wright LL, Anderson LR, Results of parallel randomized and nonrandomized clinical trials. N Kaplan EL. Once daily therapy for streptococcal pharyngitis with ce- fadroxil. J Pediatr 1986; 109:531–7.
122. Paradise JL, Bluestone CD, Colborn DK, Bernard BS, Rockette HE, 133. Jackson H. Prevention of rheumatic fever. A comparative study of Kurs-Lasky M. Tonsillectomy and adenotonsillectomy for recurrent clindamycin palmitate and ampicillin in the treatment of group A throat infection in moderately affected children. Pediatrics 2002; beta hemolytic streptococcal pharyngitis. Clin Pediatr (Phila) 1973; 123. Discolo CM, Darrow DH, Koltai PJ. Infectious indications for tonsil- 134. Kafetzis DA, Liapi G, Tsolia M, et al. Failure to eradicate Group A lectomy. Pediatr Clin North Am 2003; 50:445–58.
beta-haemolytic streptococci (GABHS) from the upper respiratory 124. Baugh RF, Archer SM, Mitchell RB, et al. Clinical practice guideline: ton- tract after antibiotic treatment. Int J Antimicrob Agents 2004; sillectomy in children. Otolaryngol Head Neck Surg 2011; 144:S1–30.
IDSA Guideline for GAS Pharyngitis • CID • 17

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