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All topics are updated as new evidence becomes available and ourpeer review processis complete.Literature review current through: Aug 2013. | This topic last updated: Jul 11, 2013.

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 [1]. 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 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 PANDAS

syndrome is not clear[10].

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 injectablepenicillin Gmixed 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
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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 [13].

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 (PANDAS) 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 [15]. 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 immunefactors in 50 percent of cases at one month following acute infection [16].

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 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 [16]. 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].
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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) [6].

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) [13].

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 [15].

Antibiotics for group A streptococcus Antibiotic options for treatment of GAS pharyngitis include

penicillin (and other related agents includingampicillinandamoxicillin), cephalosporins, macrolides,

andclindamycin[19]. Sulfonamides 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 procainepenicillin Gin oil

containing aluminum monostearate; this preparation has since been supplanted by benzathine penicillin

G. There are data suggesting that benzathine penicillin G is effective for primary prevention of rheumatic

fever, although they are not definitive [21]. 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 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;

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 Oralpenicillin Vis 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".)

Amoxicillinis 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 GI absorption [43,44]. In addition, amoxicillin has activity

against the common pathogens that cause otitis media (which presents concurrently with GAS
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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 benzathinepenicillin G(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 is the combination of 900,000 units of benzathine penicillin

G plus 300,000 units of procaine penicillin.

Cephalosporins are acceptable alternatives in patients with recurrent GAS infection but are not

recommended as first line therapy [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 are more expensive than penicillin and may facilitate

development of antibiotic resistance [46,47]. (See'Recurrent infection'below.)

Antibiotic therapy directed against beta-lactamase producing upper respiratory tract flora (such

asamoxicillin-clavulanate) remains controversial and is not indicated in patients with acute pharyngitis

[2,56,57].

For patients with beta-lactam hypersensitivity, cephalosporins (cefuroxime,cefpodoxime,cefdinir,

andceftriaxone) may be used [38,44-50], in the absence of history of life threatening allergic reaction;

cross reactivity with penicillin is less likely for later generation cephalosporins than first generation

cephalosporins [45,58-60]. Macrolides (clarithromycin,azithromycinorerythromycin) 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,clindamycinis an appropriate choice [61].

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 withcefpodoxime,cefdinir, orazithromycinis 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].

Attempts to treat GAS pharyngitis with a single daily dose of penicillin have been unsuccessful. Although

some data suggest that once dailyamoxicillinmay 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,azithromycinand some cephalosporins

(includingcefixime,cefpodoxime,cefadroxilandcefdinir) are effective for eradication of pharyngeal

streptococci with once daily dosing [69,81-84].

Antibiotics for other organisms The differential diagnosis of acute pharyngitis is outlined separately

(table 2). (See"Evaluation of acute pharyngitis in adults".)
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The approach to treatment of infection due to streptococcus other than group A, influenza, infectious

mononucleosis, primary HIV infection, Neisseria gonorrhoeae, Mycoplasma pneumoniae, Chlamydophila

pneumoniae, and Corynebacterium diphtheriae is discussed separately. (See related topics.)

The approach to treatment of infection due to F. 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 Lemierres syndrome. Some favor empiric treatment with

penicillins or cephalosporins 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 Lemierres

syndrome [85,86]. Therefore, we favor antibiotic therapy for pharyngitis only in the setting of positive

diagnostic data [41]. (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

areerythromycinorazithromycin; data are limited to case reports and in vitro studies [87,88]. 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 [88].Clindamycin,doxycycline,ciprofloxacin,

andvancomycinare 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

[89,90].

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 [90]

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 [91]. Repeat treatment should be administered with an agent with greater beta-lactamase

stability than the previous agent [56]. If a penicillin was used for initial therapy, repeat treatment

withamoxicillin-clavulanateor 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 [89,91,92]:
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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 [56].

If adherence is uncertain, intramuscular benzathinepenicillin Gmay be chosen as the second course of

therapy. If a full course of penicillin was completed as initial therapy, a first generation cephalosporin

(such ascephalexin,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 includeamoxicillin-clavulanateorclindamycin.

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

withclindamycinoramoxicillin-clavulanatemay be beneficial since these agents have demonstrated high

eradication rates for pharyngeal streptococci (table 1)[56,61,93]. (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 [94,95]. This was

illustrated in a randomized trial including 187 children with recurrent pharyngitis, of whom 95 were

managed with tonsillectomy [94]. 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",

section on 'Recurrent infection'.)

Antibiotic failure in the treatment of streptococcal tonsil lopharyngitis is discussed separately.

(See"Antibiotic failure in the treatment of streptococcal tonsillopharyngitis".)

PREVENTION

Carriers In general, GAS resides in the oropharynx of streptococcus carriers in the absence of host

immunologic response to the organism [96]. 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 [91].

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
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tend to have very low 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[96]. Moreover, eradication of GAS from

the upper respiratory tract of carriers is much more difficult than eradication of GAS from patient with

acute infections [50,89,97]. In general, except for the circumstances described above, streptococcus

carriers do not require antimicrobial therapy. (See'Follow-up'above.)

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 [98,99]. 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.

INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The

Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at

the 5th

to 6th

grade reading level, and they answer the four or five key questions a patient might have

about a given condition. These articles are best for patients who want a general overview and who prefer

short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated,

and more detailed. These articles are written at the 10th

to 12th

grade reading level and are best for

patients who want in-depth information and are comfortable with some medical jargon.

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.)

Basics topics (see"Patient information: Sore throat in adults (The Basics)"and"Patientinformation: Strep throat in children (The Basics)"and"Patient information: Scarlet fever (The

Basics)")

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 (see'Goals of therapy'above):

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

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.)
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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.)

Oralpenicillin Vis the agent of choice for treatment of GAS pharyngitis in many clinical settings

given its proven efficacy, safety, narrow spectrum, and low cost.Amoxicillinis often used in place

of oral penicillin in children, since the taste of the amoxicillin suspension is more palatable thanthat of penicillin (table 1). First-generation cephalosporins are an acceptable alternative to

penicillin and amoxicillin 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 benzathinepenicillin Gmay 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

culture data (Grade 2C). We suggesterythromycinorazithromycinfor treatment of pharyngitis

due to A. 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.)
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