Disclosures: Michael E Pichichero, MD Nothing to disclose. Daniel J Sexton, MD Grant/Research/Clinical Trail Support: Cubist [C. difficile infection (Fidaxomycin)]. Consultant/Advisory Boards: Johnson & Johnson [Pelvic mesh-related infection]; Sterilis [Medical waste disposal systems]. Other Financial Interest: National Football League [Infection control program]. Morven S Edwards, MD Consultant/Advisory Boards: Novartis Vaccines [Group B streptococcus]. Elinor L Baron, MD, DTMH Employee of UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
INTRODUCTION — Group A streptococcal (GAS) tonsillopharyngitis presents with abrupt onset of sore throat, tonsillar exudate, tender cervical adenopathy, and fever, followed by spontaneous resolution within two to five days. Patients with sore throat lasting longer than one week usually do not have GAS tonsillopharyngitis.
Issues related to treatment and prevention of group A streptococcal tonsillopharyngitis will be reviewed here . A general approach to patients with pharyngitis and the factors responsible for antibiotic failure are discussed separately. (See "Evaluation of acute pharyngitis in adults" and "Approach to diagnosis of acute infectious pharyngitis in children and adolescents" and "Antibiotic failure in the treatment of streptococcal tonsillopharyngitis".)
GOALS OF THERAPY — Goals of antimicrobial therapy for eradication of group A Streptococcus (GAS) from the pharynx in the setting of acute streptococcal pharyngitis include:
●Reducing duration and severity of clinical signs and symptoms, including suppurative complications
●Reducing incidence of nonsuppurative complications (eg, acute rheumatic fever)
●Reducing transmission to close contacts by reducing infectivity
Considerations of treatment include ease of antibiotic administration and limited expense with as few adverse effects as possible [2-4].
Reducing clinical symptoms — Antibiotic therapy is most beneficial for hastening resolution of symptoms if instituted within the first two days of illness [5-9]. Antibiotic therapy is also beneficial for reducing suppurative complications such as peritonsillar abscess, cervical lymphadenitis, and mastoiditis. Additional issues related to antibiotic therapy for reducing clinical symptoms are discussed further below. (See 'Timing of therapy' below.)
Reducing nonsuppurative complications — Antibiotic therapy is primarily helpful for reducing the incidence of acute rheumatic fever as a nonsuppurative complication of GAS pharyngitis. The role of antibiotic therapy in decreasing the nonsuppurative complications of glomerulonephritis and pediatric autoimmune neuropsychiatric disorder associated with group A streptococci (PANDAS) syndrome is not clear .
Acute rheumatic fever — Although symptoms of GAS pharyngitis resolve without antibiotic therapy, persistence of the organism in the upper respiratory tract elicits an immune response that can set the stage for subsequent risk of acute rheumatic fever (ARF) if the strain is rheumatogenic and the host is genetically predisposed. In some populations, group G and group C streptococci may also play a role in ARF pathogenesis [11,12]. (See "Epidemiology and pathogenesis of acute rheumatic fever" and "Clinical manifestations and diagnosis of acute rheumatic fever", section on 'Predisposing factors'.)
The efficacy of penicillin for primary prevention of ARF was established in the early 1950s when military recruits with GAS tonsillopharyngitis received injectable penicillin G mixed in peanut oil or sesame oil with 2 percent aluminum monostearate [13,14]. GAS eradication and ARF primary prevention were optimized with injection schedules that provided at least 9 to 11 days of penicillin.
Subsequently, evaluation of GAS tonsillopharyngitis therapies has been based upon GAS eradication from the upper respiratory tract; it is assumed that such eradication is an adequate surrogate marker for efficacy in primary prevention of rheumatic fever. Antibiotic therapy can be helpful for prevention of rheumatic fever if initiated up to nine days following onset of symptoms .
Glomerulonephritis — Children younger than seven years of age appear to be at greatest risk of poststreptococcal glomerulonephritis. Although antibiotic therapy has efficacy for primary prevention of acute rheumatic fever, the role of antibiotics in the setting of GAS tonsillopharyngitis for prevention of poststreptococcal glomerulonephritis is not certain. (See "Differential diagnosis and evaluation of glomerular disease", section on 'Hematuria following upper respiratory infection'.)
PANDAS syndrome — Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci is discussed separately. It is not clear whether antibiotic therapy for GAS pharyngitis reduces the incidence of this syndrome. (See "Complications of streptococcal tonsillopharyngitis", section on 'PANDAS syndrome'.)
Reducing transmission — The rate of GAS transmission from an infectious case to close contacts (such as a family or school setting) is approximately 35 percent. Antibiotic treatment does have a role for preventing transmission of GAS; after 24 hours of treatment with penicillin, subsequent cultures are negative in about 80 percent of cases . Data on the duration of contagion for alternative antibiotics are not available. In untreated patients, GAS is eliminated from the upper respiratory tract by host immune factors in 50 percent of cases at one month following acute infection .
Additional issues related to antibiotic therapy for reducing transmission are discussed further below. (See 'Follow-up' below.)
TREATMENT — Antimicrobial therapy is warranted for patients with symptomatic pharyngitis if the presence of group A streptococci (GAS) in the pharynx is confirmed by culture or rapid antigen detection testing (RADT). The approach to establishing the diagnosis of acute streptococcal pharyngitis is discussed in detail separately. (See "Evaluation of acute pharyngitis in adults", section on 'Identifying patients with GAS'.)
Antimicrobial therapy may also be administered to mitigate the clinical course of pharyngitis due to group C and group G streptococci. The approach to antibiotic selection is as outlined in the following sections. However, treatment need not continue for 10 days since acute rheumatic fever is not a complication of infection due to these organisms; five days of treatment is sufficient [2,17,18]. (See "Group C and group G streptococcal infection".)
In general, antimicrobial therapy is of no proven benefit for treatment of pharyngitis due to bacteria other than Streptococcus (with the exception of relatively rare infections caused by other bacterial pathogens such as Corynebacterium diphtheriae and Neisseria gonorrhoeae). Such therapy unnecessarily exposes patients to the expense and potential hazards of antimicrobial drugs and contributes to the emergence of antibiotic resistant bacteria.
Timing of therapy — If clinical and/or epidemiologic factors point to a high index of suspicion for GAS pharyngitis while laboratory results are pending, it is appropriate to initiate empiric antimicrobial therapy. However, if laboratory testing does not confirm the diagnosis of GAS pharyngitis, antimicrobial therapy should be discontinued.
In the natural history of GAS pharyngitis, the incubation period is two to four days. Fever and constitutional symptoms usually resolve within three to four days, even in the absence of antimicrobial therapy . Clinical improvement has been observed up to 48 hours sooner in patients receiving penicillin versus placebo within the first two days of illness [5-9].
There is some concern that early therapy may suppress host antibody response and thereby increase risk for recurrent pharyngitis. In a study of 142 children with presumed GAS pharyngitis, those treated with penicillin at the initial office visit had a higher incidence of recurrent infection than those for whom treatment was delayed at least 48 hours (recurrent infection occurred eight times more frequently) .
Nonetheless, delaying treatment is not warranted in most cases of GAS tonsillopharyngitis. It may be a useful strategy for patients who have frequent, recurrent, mild to moderate infections to allow development of immunity to the infecting strain without increasing the risk of acute rheumatic fever. Antibiotic therapy delayed for up to nine days following onset of symptoms is still helpful for prevention of rheumatic fever (although may be less effective for prevention of suppurative complications) . However, this approach should not be considered if the patient is severely ill or if highly virulent or rheumatogenic strains are actively circulating within a community. Patients are considered no longer contagious after 24 hours of antibiotic therapy .
Antibiotics for group A Streptococcus — Antibiotic options for treatment of GAS pharyngitis include penicillin (and other related agents including ampicillin and amoxicillin), cephalosporins, macrolides, and clindamycin . Sulfonamides, fluoroquinolones, and tetracyclines should NOT be used for treatment of GAS pharyngitis because of high rates of resistance to these agents and their frequent failure to eradicate even susceptible organisms from the pharynx.
Intramuscular penicillin is the only therapy that has been shown to prevent initial attacks of rheumatic fever in controlled studies [14,20]. These studies were performed with penicillin G procaine in oil containing aluminum monostearate; this preparation has since been supplanted by penicillin G benzathine. There are data suggesting that penicillin G benzathine is effective for primary prevention of rheumatic fever, although they are not definitive . Other antimicrobials have been shown to effectively eradicate GAS from the upper respiratory tract, and it is assumed that such eradication is a surrogate for efficacy in primary prevention of rheumatic fever.
Resistance — Antimicrobial resistance has not been a significant issue in the treatment of GAS. No clinical isolate of GAS has demonstrated penicillin resistance, likely due to the organism's lack of altered penicillin-binding proteins and/or inefficient gene transfer mechanisms for resistance [22,23]. However, streptococcal strains tolerant to penicillin (eg, strains inhibited but not killed by penicillin in vitro, with ratio of minimum bactericidal concentration to minimum inhibitory concentration [MIC] of ≥32) have been described [24-27]. The clinical significance of such strains is not clear; they have been isolated in the setting of outbreaks in which penicillin treatment failure was observed, but there was no difference in failure rates among tolerant and susceptible strains. (See "Antibiotic failure in the treatment of streptococcal tonsillopharyngitis".)
There have been reports of relatively high levels of resistance to macrolide antibiotics in some regions of the United States and Asia; given the increasing use of macrolides for treatment of upper and lower respiratory tract infections, clinicians should be cognizant of local patterns of antimicrobial resistance [28-37].
Selection — Oral penicillin V is the agent of choice for treatment of GAS pharyngitis given its proven efficacy, safety, narrow spectrum, and low cost [2,38-42]. The appropriate duration is 10 days of therapy; dosing is outlined in the Table (table 1). This approach is extrapolated from studies performed in the 1950s demonstrating that treatment of streptococcal pharyngitis with intramuscular penicillin prevents acute rheumatic fever [14,20]. (See "Treatment and prevention of acute rheumatic fever".)
Amoxicillin is often used in place of oral penicillin in children, since the taste of the amoxicillin suspension is more palatable than that of penicillin. Some data suggest that oral amoxicillin may be marginally superior to penicillin, most likely due to better gastrointestinal (GI) absorption [43,44]. In addition, amoxicillin has activity against one-third of the common pathogens that cause otitis media (which presents concurrently with GAS tonsillopharyngitis in up to 15 percent of children, particularly those under four years of age). Dosing is outlined in the Table (table 1). (See "Acute otitis media in children: Treatment", section on 'Initial antimicrobial therapy'.)
Intramuscular penicillin G benzathine (single dose) may be administered to patients who cannot complete a 10-day course of oral therapy or to patients at enhanced risk for rheumatic fever (eg, those with history of previous rheumatic heart disease and/or living in crowded conditions). Injections of benzathine penicillin provide bactericidal levels against GAS for 21 to 28 days. The addition of procaine penicillin alleviates some of the discomfort associated with benzathine injections and may favorably influence the initial clinical response. The preferred product in children is the combination of 900,000 units of benzathine penicillin G plus 300,000 units of procaine penicillin (Bicillin C-R 900/300). (See Penicillin G benzathine-penicillin G procaine: Drug information). Dosing is outlined in the Table (table 1).
Cephalosporins are acceptable alternatives in patients with recurrent GAS infection but are not recommended as first-line therapy in national guidelines [45-52]. Cephalosporins have demonstrated better microbiologic and clinical cure rates than penicillin; these differences appear to be greater among children than adults, and some favor use of first-generation cephalosporins as first-line therapy in this group [53-55]. However, second- and third-generation cephalosporins may facilitate development of antibiotic resistance and are not favored as first-line therapy [46,47]. (See 'Recurrent infection' below.)
Antibiotic therapy directed against beta-lactamase-producing upper respiratory tract flora (such as amoxicillin-clavulanate) remains controversial and is not indicated in patients with acute pharyngitis, although it would be effective [2,56,57].
For patients with beta-lactam hypersensitivity, cephalosporins (cefuroxime, cefpodoxime, cefdinir, and ceftriaxone) may be used [38,44-50], in the absence of history of life-threatening allergic reaction to penicillin; cross reactivity with penicillin is not likely for later-generation cephalosporins than first-generation cephalosporins [45,58-60]. Macrolides (clarithromycin, azithromycin, or erythromycin) are an acceptable alternative for penicillin-allergic patients, depending on local resistance patterns [28,31-36]. For the rare patient with an erythromycin-resistant strain of GAS who is unable to tolerate beta-lactam agents, clindamycin is an appropriate choice .
Duration — In general, the conventional duration of oral antibiotic therapy to achieve maximal pharyngeal GAS eradication rates is 10 days, even though patients usually improve clinically within the first few days of treatment [62,63]. If penicillin is discontinued after three days of therapy, the probability of relapse is higher than if penicillin is discontinued after seven days of treatment (50 versus 34 percent, respectively) [14,16,20].
Five days of therapy with cefpodoxime, cefdinir, or azithromycin is an acceptable alternative approach, with rates of bacteriologic and clinical cure of streptococcal pharyngitis comparable with that of the conventional 10-day course of penicillin [33-36,41,64-76]. Three injections of ceftriaxone on sequential days (or every other day) are needed for optimal eradication.
Attempts to treat GAS pharyngitis with a single daily dose of penicillin have been unsuccessful. Although some data suggest that once-daily amoxicillin may be sufficient for treatment of GAS pharyngitis, others have shown that this approach is not adequate for effective eradication; further investigation is needed [77-80]. Among the alternative agents, azithromycin and some cephalosporins (including cefixime, cefpodoxime, cefadroxil, and cefdinir) are effective for eradication of pharyngeal streptococci with once-daily dosing [69,81-84].
The approach to treatment of infection due to Streptococcus other than group A, influenza, infectious mononucleosis, primary HIV infection, N. gonorrhoeae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Corynebacterium diphtheriae is discussed separately. (See related topics.)
The approach to treatment of infection due to Fusobacterium necrophorum is uncertain; further study is needed to better define the role of F. necrophorum in the epidemiology of pharyngitis and the associated risk between F. necrophorum pharyngitis and Lemierre’s syndrome. Some favor empiric treatment in the setting of negative diagnostic test results but at least three Centor criteria (fever, tonsillar exudate, swollen tender cervical adenopathy, or lack of cough) among patients 15 to 30 years of age, although it is uncertain whether this approach is effective for prevention of Lemierre’s syndrome [85-87]. In general, we favor treatment for pharyngitis only in the setting of a positive diagnostic test . Antibiotic therapy for pharyngitis attributed to F. necrophorum should consist of a penicillin or cephalosporin; azithromycin lacks activity. (See "Suppurative (septic) thrombophlebitis", section on 'Jugular vein' and "Evaluation of acute pharyngitis in adults", section on 'Evaluation'.)
The antibiotics of choice for treatment of infection due to Arcanobacterium haemolyticum are erythromycin or azithromycin; data are limited to case reports and in vitro studies [88,89]. In vitro studies show most strains to be susceptible to beta-lactam agents, although treatment failure may occur because of poor penetration into the intracellular space . Clindamycin, doxycycline, ciprofloxacin, and vancomycin are also effective agents.
Follow-up — Patients with GAS pharyngitis should have improvement in clinical symptoms within three to four days of initiating antibiotic therapy. Failure to observe a clinical response to antibiotics should prompt diagnostic reconsideration or the possibility of a suppurative complication. If acute streptococcal pharyngitis was diagnosed by rapid testing, the result may represent a false-positive finding; if the diagnosis was made by culture, the patient may be a pharyngeal carrier whose symptoms are likely attributable to an alternate process. (See 'Carriers' below.)
In general, test of cure is not necessary for asymptomatic patients or their close contacts following completion of a course of antimicrobial therapy. The majority of patients with GAS remaining in their upper respiratory tracts after completing a course of antimicrobial therapy are Streptococcus carriers [90,91].
However, follow-up test of cure is appropriate testing for asymptomatic index patients and their asymptomatic household contacts in the following circumstances:
●Individuals with history of rheumatic fever
●Individuals who develop acute pharyngitis during an outbreak of acute rheumatic fever or acute poststreptococcal glomerulonephritis 
●Spread of GAS among several family members
Asymptomatic patients and asymptomatic household contacts in the above circumstances with positive laboratory results should receive a standard course of antimicrobial therapy with one of the agents outlined above . Repeat treatment should be administered with an agent with greater beta-lactamase stability than the previous agent . If a penicillin was used for initial therapy, repeat treatment with amoxicillin-clavulanate or a first-generation cephalosporin may be used; if initial treatment was with a first-generation cephalosporin, a second- or third-generation cephalosporin may be used. (See "Evaluation of acute pharyngitis in adults" and 'Antibiotics for group A Streptococcus' above.)
Recurrent infection — In the setting of recurrent acute pharyngitis with positive repeat diagnostic testing, there are several possible explanations [90,92,93]:
●Persistence of Streptococcus carriage in the setting of viral infection
●Nonadherence with the prescribed antimicrobial regimen
●New infection with GAS acquired from household or community contacts
●Treatment failure (eg, repeat episode of pharyngitis caused by the original infecting strain); treatment failure is rare.
In the setting of a second episode of acute pharyngitis with positive repeat diagnostic testing, a repeat course of treatment is appropriate (table 1). Repeat treatment should be administered with an agent with greater beta-lactamase stability than the previous agent .
If adherence is uncertain, intramuscular penicillin G benzathine may be chosen as the second course of therapy. If a full course of penicillin was completed as initial therapy, a first-generation cephalosporin (such as cephalexin, cefadroxil) may be used; if a first-generation cephalosporin was used for initial therapy, a second- or third-generation cephalosporin (such as cefpodoxime, cefdinir) may be used. Alternative agents include amoxicillin-clavulanate or clindamycin.
It is not necessary to perform follow-up testing after the second course of therapy unless the patient remains or becomes symptomatic or unless special circumstances as outlined above are present. (See 'Antibiotics for group A Streptococcus' above and 'Follow-up' above.)
In the setting of multiple recurrent episodes, it may be difficult to distinguish true GAS pharyngitis from viral pharyngitis in the setting of streptococcal carriage. It is likely that most of these patients are carriers experiencing nonstreptococcal infections. This may be discernible by evaluating for the presence of GAS during asymptomatic intervals and/or by typing streptococcal isolates obtained during distinct episodes (with the expertise of a specialized laboratory). In these circumstances, treatment with clindamycin or amoxicillin-clavulanate may be beneficial since these agents have demonstrated high eradication rates for pharyngeal streptococci carriage (table 1) [56,61,94]. (See 'Carriers' below.)
For patients with as many as six GAS infections in a single year or three to four episodes in two consecutive years, tonsillectomy may be an appropriate therapeutic consideration [95,96]. This was illustrated in a randomized trial including 187 children with recurrent pharyngitis, of whom 95 were managed with tonsillectomy . The incidence of pharyngitis during the first two years of follow-up was significantly lower among the tonsillectomy group. (See "Tonsillectomy and adenoidectomy in children: Indications and contraindications", section on 'Recurrent infection'.)
Antibiotic failure in the treatment of streptococcal tonsillopharyngitis is discussed separately. (See "Antibiotic failure in the treatment of streptococcal tonsillopharyngitis".)
Carriers — In general, group A Streptococcus (GAS) resides in the oropharynx of Streptococcus carriers in the absence of host immunologic response to the organism . In temperate climates during the winter and spring, up to 20 percent of asymptomatic school-aged children may be carriers. About 25 percent of asymptomatic individuals in the households of index patients harbor GAS in their upper respiratory tracts . Streptococcal carriage may persist for many months. (See "Antibiotic failure in the treatment of streptococcal tonsillopharyngitis", section on 'Streptococcal carriage'.)
Carriers may demonstrate evidence of GAS in the upper respiratory tract during an episode of viral pharyngitis, suggesting acute streptococcal pharyngitis. In these circumstances, clinically distinguishing viral from streptococcal pharyngitis can be difficult. Useful clues may include patient age, season, local epidemiology, and the nature of presenting signs and symptoms. In addition, pharyngeal strep carriers tend to have low antistreptolysin O (ASO) titers; they may be just above detectable. (See "Evaluation of acute pharyngitis in adults".)
Streptococcus carriers are unlikely to spread the organism to close contacts and are at very low risk for developing suppurative complications or acute rheumatic fever . Moreover, eradication of GAS from the upper respiratory tract of carriers is much more difficult than eradication of GAS from patients with acute infection [50,90,98]. In general, except for the circumstances described above, Streptococcus carriers do not require antimicrobial therapy. (See 'Follow-up' above.)
Foodborne illness — Streptococcal contamination of food has been implicated in foodborne outbreaks of pharyngitis [99-103], and foodborne transmission of GAS pharyngitis by asymptomatic food service workers with nasopharyngeal carriage has been reported [102,104,105]. Factors that can reduce foodborne transmission of GAS pharyngitis include thorough cooking, complete reheating, and use of gloves while handling food [99,106].
Prophylaxis — Continuous antimicrobial prophylaxis is only appropriate for prevention of recurrent rheumatic fever in patients who have experienced a previous episode of rheumatic fever. (See "Treatment and prevention of acute rheumatic fever", section on 'Secondary prevention'.)
Vaccination — There is no vaccine against GAS available for clinical use, although development of this preventive measure is under investigation [107,108]. An important area of uncertainty is whether vaccine-induced antibodies may cross-react with host tissue to produce nonsuppurative sequelae in the absence of clinical infection.
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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient information: Sore throat in children (Beyond the Basics)" and "Patient information: Sore throat in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Goals of antimicrobial therapy for eradication of group A Streptococcus (GAS) from the pharynx in the setting of acute streptococcal pharyngitis include:
•Reducing duration and severity of clinical signs and symptoms, including suppurative complications
•Reducing incidence of nonsuppurative complications (eg, acute rheumatic fever)
•Reducing transmission to close contacts by reducing infectivity (see 'Goals of therapy' above)
●We recommend initiating treatment with antimicrobial therapy for patients with symptomatic pharyngitis if the presence of group A streptococci in the pharynx is confirmed by culture or rapid antigen detection testing (RADT) (Grade 1A). (See 'Treatment' above.)
●We suggest initiating treatment with antimicrobial therapy for patients whose clinical and/or epidemiologic factors point to a high index of suspicion for GAS pharyngitis while laboratory results are pending (Grade 2B). (See 'Treatment' above.)
●Oral penicillin V is the agent of choice for treatment of GAS pharyngitis in many clinical settings given its proven efficacy, safety, narrow spectrum, and low cost. Amoxicillin is often used in place of oral penicillin in children, since the taste of the amoxicillin suspension is more palatable than that of penicillin (table 1). First-generation cephalosporins are an acceptable alternative to penicillin and amoxicillin, especially in the setting of treatment failure or beta-lactam hypersensitivity. (See 'Selection' above.)
●Although most patients improve clinically within the first few days of treatment, the conventional duration of oral antibiotic therapy is 10 days to achieve maximal pharyngeal GAS eradication rates. Intramuscular penicillin G benzathine may be administered to patients who cannot complete a 10-day course of oral therapy. (See 'Duration' above.)
●We suggest NOT treating with antibiotics for pharyngitis in the absence of positive diagnostic data (Grade 2C). We suggest erythromycin or azithromycin for treatment of pharyngitis due to Arcanobacterium haemolyticum (Grade 2C). (See 'Antibiotics for other organisms' above.)
●In general, test of cure is not necessary for asymptomatic patients or their close contacts following completion of a course of antimicrobial therapy, except in unique circumstances. (See 'Follow-up' above.)
●We suggest a repeat course of treatment for patients with a repeat episode of acute pharyngitis and positive repeat diagnostic testing (Grade 2C). Patients warranting a repeat course of treatment may receive an agent with greater beta-lactamase stability than the previous agent. (See 'Recurrent infection' above.)
●Patients who are long-term streptococcal carriers may develop multiple episodes of pharyngitis due to viral infection. In such cases, repeatedly positive cultures or rapid antigen tests for GAS may be misleading, and further treatment for streptococcal pharyngitis may not be warranted. Carriers are unlikely to spread the organism to close contacts and are at very low risk for developing suppurative complications or acute rheumatic fever. Moreover, eradication of GAS from the upper respiratory tract of carriers can be difficult and is not necessary. (See 'Carriers' above.)
- Wessels MR. Clinical practice. Streptococcal pharyngitis. N Engl J Med 2011; 364:648.
- Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2009; 119:1541.
- Pichichero ME. Controversies in the treatment of streptococcal pharyngitis. Am Fam Physician 1990; 42:1567.
- Pichichero ME. Group A streptococcal tonsillopharyngitis: cost-effective diagnosis and treatment. Ann Emerg Med 1995; 25:390.
- Randolph MF, Gerber MA, DeMeo KK, Wright L. Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis. J Pediatr 1985; 106:870.
- Pichichero ME, Disney FA, Talpey WB, et al. Adverse and beneficial effects of immediate treatment of Group A beta-hemolytic streptococcal pharyngitis with penicillin. Pediatr Infect Dis J 1987; 6:635.
- Krober MS, Bass JW, Michels GN. Streptococcal pharyngitis. Placebo-controlled double-blind evaluation of clinical response to penicillin therapy. JAMA 1985; 253:1271.
- Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev 2000; :CD000023.
- Gilbert GG, Pruitt BE. School health education in the United States. Hygie 1984; 3:10.
- Potter EV, Svartman M, Mohammed I, et al. Tropical acute rheumatic fever and associated streptococcal infections compared with concurrent acute glomerulonephritis. J Pediatr 1978; 92:325.
- McDonald M, Currie BJ, Carapetis JR. Acute rheumatic fever: a chink in the chain that links the heart to the throat? Lancet Infect Dis 2004; 4:240.
- McDonald MI, Towers RJ, Andrews RM, et al. Low rates of streptococcal pharyngitis and high rates of pyoderma in Australian aboriginal communities where acute rheumatic fever is hyperendemic. Clin Infect Dis 2006; 43:683.
- Catanzaro FJ, Stetson CA, Morris AJ, et al. The role of the streptococcus in the pathogenesis of rheumatic fever. Am J Med 1954; 17:749.
- Denny FW, Wannamaker LW, Brink WR, et al. Prevention of rheumatic fever; treatment of the preceding streptococcic infection. J Am Med Assoc 1950; 143:151.
- Snellman LW, Stang HJ, Stang JM, et al. Duration of positive throat cultures for group A streptococci after initiation of antibiotic therapy. Pediatrics 1993; 91:1166.
- Brink WR, Rammelkamp CH Jr, Denny FW, Wannamaker LW. Effect in penicillin and aureomycin on the natural course of streptococcal tonsillitis and pharyngitis. Am J Med 1951; 10:300.
- Meier FA, Centor RM, Graham L Jr, Dalton HP. Clinical and microbiological evidence for endemic pharyngitis among adults due to group C streptococci. Arch Intern Med 1990; 150:825.
- Turner JC, Hayden FG, Lobo MC, et al. Epidemiologic evidence for Lancefield group C beta-hemolytic streptococci as a cause of exudative pharyngitis in college students. J Clin Microbiol 1997; 35:1.
- Betriu C, Sanchez A, Gomez M, et al. Antibiotic susceptibility of group A streptococci: a 6-year follow-up study. Antimicrob Agents Chemother 1993; 37:1717.
- Wannamaker LW, Rammelkamp CH Jr, Denny FW, et al. Prophylaxis of acute rheumatic fever by treatment of the preceding streptococcal infection with various amounts of depot penicillin. Am J Med 1951; 10:673.
- CHAMOVITZ R, CATANZARO FJ, STETSON CA, RAMMELKAMP CH Jr. Prevention of rheumatic fever by treatment of previous streptococcal infections. I. Evaluation of benzathine penicillin G. N Engl J Med 1954; 251:466.
- Coonan KM, Kaplan EL. In vitro susceptibility of recent North American group A streptococcal isolates to eleven oral antibiotics. Pediatr Infect Dis J 1994; 13:630.
- Horn DL, Zabriskie JB, Austrian R, et al. Why have group A streptococci remained susceptible to penicillin? Report on a symposium. Clin Infect Dis 1998; 26:1341.
- Van Asselt GJ, Mouton RP. Detection of penicillin tolerance in Streptococcus pyogenes. J Med Microbiol 1993; 38:197.
- Brett MS. Antibiotic susceptibilities and penicillin tolerance of group A streptococci isolated in New Zealand in 1990. J Antimicrob Chemother 1994; 33:668.
- Dagan R, Ferne M, Sheinis M, et al. An epidemic of penicillin-tolerant group A streptococcal pharyngitis in children living in a closed community: mass treatment with erythromycin. J Infect Dis 1987; 156:514.
- Stevens DL, Yan S, Bryant AE. Penicillin-binding protein expression at different growth stages determines penicillin efficacy in vitro and in vivo: an explanation for the inoculum effect. J Infect Dis 1993; 167:1401.
- Martin JM, Green M, Barbadora KA, Wald ER. Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh. N Engl J Med 2002; 346:1200.
- Seppälä H, Klaukka T, Vuopio-Varkila J, et al. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. Finnish Study Group for Antimicrobial Resistance. N Engl J Med 1997; 337:441.
- Cornaglia G, Ligozzi M, Mazzariol A, et al. Resistance of Streptococcus pyogenes to erythromycin and related antibiotics in Italy. The Italian Surveillance Group for Antimicrobial Resistance. Clin Infect Dis 1998; 27 Suppl 1:S87.
- Derrick CW, Dillon HC. Erythromycin therapy for streptococcal pharyngitis. Am J Dis Child 1976; 130:175.
- Richter SS, Heilmann KP, Beekmann SE, et al. Macrolide-resistant Streptococcus pyogenes in the United States, 2002-2003. Clin Infect Dis 2005; 41:599.
- Bachand RT Jr. A comparative study of clarithromycin and penicillin VK in the treatment of outpatients with streptococcal pharyngitis. J Antimicrob Chemother 1991; 27 Suppl A:75.
- Still JG, Hubbard WC, Poole JM, et al. Comparison of clarithromycin and penicillin VK suspensions in the treatment of children with streptococcal pharyngitis and review of currently available alternative antibiotic therapies. Pediatr Infect Dis J 1993; 12:S134.
- Hooton TM. A comparison of azithromycin and penicillin V for the treatment of streptococcal pharyngitis. Am J Med 1991; 91:23S.
- Casey JR, Pichichero ME. Higher dosages of azithromycin are more effective in treatment of group A streptococcal tonsillopharyngitis. Clin Infect Dis 2005; 40:1748.
- Logan LK, McAuley JB, Shulman ST. Macrolide treatment failure in streptococcal pharyngitis resulting in acute rheumatic fever. Pediatrics 2012; 129:e798.
- Gerber MA, Spadaccini LJ, Wright LL, et al. Twice-daily penicillin in the treatment of streptococcal pharyngitis. Am J Dis Child 1985; 139:1145.
- Snow V, Mottur-Pilson C, Cooper RJ, et al. Principles of appropriate antibiotic use for acute pharyngitis in adults. Ann Intern Med 2001; 134:506.
- American Academy of Pediatrics. Group A Streptococcal infections. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 29th ed, Pickering LK (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2012.
- 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; 55:1279.
- van Driel ML, De Sutter AI, Keber N, et al. Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database Syst Rev 2013; 4:CD004406.
- Gopichand I, Williams GD, Medendorp SV, et al. Randomized, single-blinded comparative study of the efficacy of amoxicillin (40 mg/kg/day) versus standard-dose penicillin V in the treatment of group A streptococcal pharyngitis in children. Clin Pediatr (Phila) 1998; 37:341.
- Curtin-Wirt C, Casey JR, Murray PC, et al. Efficacy of penicillin vs. amoxicillin in children with group A beta hemolytic streptococcal tonsillopharyngitis. Clin Pediatr (Phila) 2003; 42:219.
- Pichichero ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics 2005; 115:1048.
- Casey JR, Pichichero ME. Meta-analysis of cephalosporins versus penicillin for treatment of group A streptococcal tonsillopharyngitis in adults. Clin Infect Dis 2004; 38:1526.
- Casey JR, Pichichero ME. Meta-analysis of cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis in children. Pediatrics 2004; 113:866.
- Bisno AL. Are cephalosporins superior to penicillin for treatment of acute streptococcal pharyngitis? Clin Infect Dis 2004; 38:1535.
- Shulman ST, Gerber MA. So what's wrong with penicillin for strep throat? Pediatrics 2004; 113:1816.
- Gerber MA, Tanz RR, Kabat W, et al. Potential mechanisms for failure to eradicate group A streptococci from the pharynx. Pediatrics 1999; 104:911.
- Linder JA, Stafford RS. Antibiotic treatment of adults with sore throat by community primary care physicians: a national survey, 1989-1999. JAMA 2001; 286:1181.
- Pavesio D, Pecco P, Peisino MG. Short-term treatment of streptococcal tonsillitis with ceftriaxone. Chemotherapy 1988; 34 Suppl 1:34.
- Evidence-Based Pediatric Infectious Diseases, Isaacs D, Elliott E, Corlbert R, et al (Eds), Blackmill Publishing, Victoria, Austrailia 2007.
- Pichichero ME, Hoeger W, Marsocci SM, et al. Variables influencing penicillin treatment outcome in streptococcal tonsillopharyngitis. Arch Pediatr Adolesc Med 1999; 153:565.
- Kaplan EL, Oakes JM, Johnson DR. Unexpected individual clinical site variation in eradication rates of group a streptococci by penicillin in multisite clinical trials. Pediatr Infect Dis J 2007; 26:1110.
- Kaplan EL, Johnson DR. Eradication of group A streptococci from the upper respiratory tract by amoxicillin with clavulanate after oral penicillin V treatment failure. J Pediatr 1988; 113:400.
- Brook I. Treatment of patients with acute recurrent tonsillitis due to group A beta-haemolytic streptococci: a prospective randomized study comparing penicillin and amoxycillin/clavulanate potassium. J Antimicrob Chemother 1989; 24:227.
- American Academy of Pediatrics. Subcommittee on Management of Sinusitis and Committee on Quality Improvement. Clinical practice guideline: management of sinusitis. Pediatrics 2001; 108:798.
- Pichichero ME, Casey JR. Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis. Otolaryngol Head Neck Surg 2007; 136:340.
- Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media. Pediatrics 2013; 131:e964.
- Tanz RR, Poncher JR, Corydon KE, et al. Clindamycin treatment of chronic pharyngeal carriage of group A streptococci. J Pediatr 1991; 119:123.
- Kaplan EL, Gooch III WM, Notario GF, Craft JC. Macrolide therapy of group A streptococcal pharyngitis: 10 days of macrolide therapy (clarithromycin) is more effective in streptococcal eradication than 5 days (azithromycin). Clin Infect Dis 2001; 32:1798.
- Altamimi S, Khalil A, Khalaiwi KA, et al. Short-term late-generation antibiotics versus longer term penicillin for acute streptococcal pharyngitis in children. Cochrane Database Syst Rev 2012; 8:CD004872.
- Cohen R, Levy C, Doit C, et al. Six-day amoxicillin vs. ten-day penicillin V therapy for group A streptococcal tonsillopharyngitis. Pediatr Infect Dis J 1996; 15:678.
- Peyramond D, Portier H, Geslin P, Cohen R. 6-day amoxicillin versus 10-day penicillin V for group A beta-haemolytic streptococcal acute tonsillitis in adults: a French multicentre, open-label, randomized study. The French Study Group Clamorange. Scand J Infect Dis 1996; 28:497.
- Gerber MA, Tanz RR. New approaches to the treatment of group A streptococcal pharyngitis. Curr Opin Pediatr 2001; 13:51.
- McCarty J, Hedrick JA, Gooch WM. Clarithromycin suspension vs penicillin V suspension in children with streptococcal pharyngitis. Adv Ther 2000; 17:14.
- Tack KJ, Henry DC, Gooch WM, et al. Five-day cefdinir treatment for streptococcal pharyngitis. Cefdinir Pharyngitis Study Group. Antimicrob Agents Chemother 1998; 42:1073.
- Pichichero ME, Gooch WM, Rodriguez W, et al. Effective short-course treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis. Ten days of penicillin V vs 5 days or 10 days of cefpodoxime therapy in children. Arch Pediatr Adolesc Med 1994; 148:1053.
- Pichichero ME. Cephalosporins are superior to penicillin for treatment of streptococcal tonsillopharyngitis: is the difference worth it? Pediatr Infect Dis J 1993; 12:268.
- Pichichero ME. Shortened regimens for pharyngitis/tonsillitis. Hosp Pract 1996; 31(Suppl 1):14.
- Falagas ME, Vouloumanou EK, Matthaiou DK, et al. Effectiveness and safety of short-course vs long-course antibiotic therapy for group a beta hemolytic streptococcal tonsillopharyngitis: a meta-analysis of randomized trials. Mayo Clin Proc 2008; 83:880.
- Mehra S, van Moerkerke M, Welck J, et al. Short course therapy with cefuroxime axetil for group A streptococcal tonsillopharyngitis in children. Pediatr Infect Dis J 1998; 17:452.
- Boccazzi A, Tonelli P, De'Angelis M, et al. Short course therapy with cefitbuten versus azithromycin in pediatric streptococcal pharyngitis. Pediatr Infect Dis J 2000; 19:963.
- Casey JR, Pichichero ME. Metaanalysis of short course antibiotic treatment for group a streptococcal tonsillopharyngitis. Pediatr Infect Dis J 2005; 24:909.
- Adam D, Scholz H, Helmerking M. Short-course antibiotic treatment of 4782 culture-proven cases of group A streptococcal tonsillopharyngitis and incidence of poststreptococcal sequelae. J Infect Dis 2000; 182:509.
- Shvartzman P, Tabenkin H, Rosentzwaig A, Dolginov F. Treatment of streptococcal pharyngitis with amoxycillin once a day. BMJ 1993; 306:1170.
- Feder HM Jr, Gerber MA, Randolph MF, et al. Once-daily therapy for streptococcal pharyngitis with amoxicillin. Pediatrics 1999; 103:47.
- 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.
- Pichichero ME, Casey JR, Block SL, et al. Pharmacodynamic analysis and clinical trial of amoxicillin sprinkle administered once daily for 7 days compared to penicillin V potassium administered four times daily for 10 days in the treatment of tonsillopharyngitis due to Streptococcus pyogenes in children. Antimicrob Agents Chemother 2008; 52:2512.
- Pichichero ME, Disney FA, Aronovitz GH, et al. Randomized, single-blind evaluation of cefadroxil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis. Antimicrob Agents Chemother 1987; 31:903.
- Block SL, Hedrick JA, Tyler RD. Comparative study of the effectiveness of cefixime and penicillin V for the treatment of streptococcal pharyngitis in children and adolescents. Pediatr Infect Dis J 1992; 11:919.
- Adam D, Hostalek U, Tröster K. 5-day cefixime therapy for bacterial pharyngitis and/or tonsillitis: comparison with 10-day penicillin V therapy. Cefixime Study Group. Infection 1995; 23 Suppl 2:S83.
- Nemeth MA, Gooch WM 3rd, Hedrick J, et al. Comparison of cefdinir and penicillin for the treatment of pediatric streptococcal pharyngitis. Clin Ther 1999; 21:1525.
- Centor RM, Allison JJ, Cohen SJ. Pharyngitis management: defining the controversy. J Gen Intern Med 2007; 22:127.
- Centor RM. Expand the pharyngitis paradigm for adolescents and young adults. Ann Intern Med 2009; 151:812.
- Cooper RJ, Hoffman JR, Bartlett JG, et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med 2001; 134:509.
- Mackenzie A, Fuite LA, Chan FT, et al. Incidence and pathogenicity of Arcanobacterium haemolyticum during a 2-year study in Ottawa. Clin Infect Dis 1995; 21:177.
- Carlson P, Renkonen OV, Kontiainen S. Arcanobacterium haemolyticum and streptococcal pharyngitis. Scand J Infect Dis 1994; 26:283.
- Kaplan EL, Gastanaduy AS, Huwe BB. The role of the carrier in treatment failures after antibiotic for group A streptococci in the upper respiratory tract. J Lab Clin Med 1981; 98:326.
- Gerber MA. Treatment failures and carriers: perception or problems? Pediatr Infect Dis J 1994; 13:576.
- Schwartz RH, Wientzen RL Jr, Pedreira F, et al. Penicillin V for group A streptococcal pharyngotonsillitis. A randomized trial of seven vs ten days' therapy. JAMA 1981; 246:1790.
- Gerber MA, Randolph MF, Chanatry J, et al. Once daily therapy for streptococcal pharyngitis with cefadroxil. J Pediatr 1986; 109:531.
- Orrling A, Stjernquist-Desatnik A, Schalén C, Kamme C. Clindamycin in persisting streptococcal pharyngotonsillitis after penicillin treatment. Scand J Infect Dis 1994; 26:535.
- Paradise JL, Bluestone CD, Bachman RZ, et al. Efficacy of tonsillectomy for recurrent throat infection in severely affected children. Results of parallel randomized and nonrandomized clinical trials. N Engl J Med 1984; 310:674.
- Alho OP, Koivunen P, Penna T, et al. Tonsillectomy versus watchful waiting in recurrent streptococcal pharyngitis in adults: randomised controlled trial. BMJ 2007; 334:939.
- Kaplan EL. The group A streptococcal upper respiratory tract carrier state: an enigma. J Pediatr 1980; 97:337.
- Shulman ST, Gerber MA, Tanz RR, Markowitz M. Streptococcal pharyngitis: the case for penicillin therapy. Pediatr Infect Dis J 1994; 13:1.
- Kemble SK, Westbrook A, Lynfield R, et al. Foodborne outbreak of group a streptococcus pharyngitis associated with a high school dance team banquet--Minnesota, 2012. Clin Infect Dis 2013; 57:648.
- Levy M, Johnson CG, Kraa E. Tonsillopharyngitis caused by foodborne group A streptococcus: a prison-based outbreak. Clin Infect Dis 2003; 36:175.
- Katzenell U, Shemer J, Bar-Dayan Y. Streptococcal contamination of food: an unusual cause of epidemic pharyngitis. Epidemiol Infect 2001; 127:179.
- Decker MD, Lavely GB, Hutcheson RH Jr, Schaffner W. Food-borne streptococcal pharyngitis in a hospital pediatrics clinic. JAMA 1985; 253:679.
- Todd EC, Greig JD, Michaels BS, et al. Outbreaks where food workers have been implicated in the spread of foodborne disease. Part 11. Use of antiseptics and sanitizers in community settings and issues of hand hygiene compliance in health care and food industries. J Food Prot 2010; 73:2306.
- Sarvghad MR, Naderi HR, Naderi-Nassab M, et al. An outbreak of food-borne group A Streptococcus (GAS) tonsillopharyngitis among residents of a dormitory. Scand J Infect Dis 2005; 37:647.
- McCormick JB, Hayes P, Feldman R. Epidemic streptococcal sore throat following a community picnic. JAMA 1976; 236:1039.
- Kaplan EL. Editorial commentary: The epidemiology of group a streptococci: a need to understand the significance of the fertile fields. Clin Infect Dis 2012; 55:488.
- McNeil SA, Halperin SA, Langley JM, et al. Safety and immunogenicity of 26-valent group a streptococcus vaccine in healthy adult volunteers. Clin Infect Dis 2005; 41:1114.
- Pichichero ME. Group A streptococcal vaccines. JAMA 2004; 292:738.