5/12/2017 Treatment and prevention of streptococcal tonsillopharyngitis - UpToDate

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Treatment and prevention of streptococcal tonsillopharyngitis

Author: Michael E Pichichero, MD

Section Editors: Daniel J Sexton, MD, Morven S Edwards, MD
Deputy Editor: Sheila Bond, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2017. | This topic last updated: Feb 16, 2017.

INTRODUCTION — Tonsillopharyngitis due to Streptococcus pyogenes, also known as group A

Streptococcus (GAS) (table 1 and table 2), 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 "Group A streptococcal
tonsillopharyngitis in children and adolescents: Clinical features and diagnosis" 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), although the severity of
signs and symptoms of GAS pharyngitis does not predict the likelihood of complications [10]. 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
[11].

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. (See "Acute rheumatic fever: Epidemiology and pathogenesis" and "Acute rheumatic fever:
Clinical manifestations and diagnosis".)

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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%
aluminum monostearate [12,13]. 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 [12].

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 "Glomerular disease: Evaluation and differential
diagnosis in adults".)

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. In one study including 47 children with pharyngitis and positive throat culture for GAS,
subsequent throat culture after 24 hours of treatment with penicillin was negative in about 80 percent of
cases [14]. In another study including 111 children with positive rapid antigen detection test (RADT) treated
with amoxicillin (50 mg/kg) by 5:00 pm on day 1, negative follow-up RADT the following morning was
observed in 91 percent of patients [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 immune factors 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 (GAS) in the pharynx is confirmed by culture or rapid antigen detection testing
(RADT) [17]. 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 [2,18,19]. (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.

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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].

Treatment is warranted for patients with negative rapid antigen detection testing but subsequent positive
culture results whose symptoms are resolving, in order to reduce the likelihood of transmission.

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) [12]. 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 [14].

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 [20]. 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 [13,21]. 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 [22]. 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 [23,24]. 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
[25-28]. 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 [29-39].

Selection — Oral penicillin V is the agent of choice for treatment of GAS pharyngitis given its proven
efficacy, safety, narrow spectrum, and low cost [2,40-44]. The appropriate duration is 10 days of therapy;
dosing is outlined in the Table (table 3). This approach is extrapolated from studies performed in the 1950s

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demonstrating that treatment of streptococcal pharyngitis with intramuscular penicillin prevents acute
rheumatic fever [13,21]. (See "Acute rheumatic fever: Treatment and prevention".)

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 [45,46]. 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 3). (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 penicillin G benzathine
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 penicillin G benzathine
plus 300,000 units of procaine penicillin (Bicillin C-R 900/300). Dosing is outlined in the Table (table 3).

Cephalosporins are acceptable alternatives in patients with recurrent GAS infection but are not
recommended as first-line therapy in national guidelines [47-54]. 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 [55-57].
However, second- and third-generation cephalosporins may facilitate development of antibiotic resistance
and are not favored as first-line therapy [48,49]. (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 [2,58,59].

For patients with penicillin hypersensitivity, cephalosporins (cefuroxime, cefpodoxime, cefdinir, and
ceftriaxone) may be used [40,46-52], in the absence of history of life-threatening allergic reaction to penicillin;
cross reactivity with penicillin is not likely for later-generation cephalosporins [47,60-62]. Macrolides
(azithromycin, clarithromycin, or erythromycin) are an acceptable alternative for penicillin-allergic patients,
depending on local resistance patterns, as resistance rates can be as high as 20 percent [2,32,34-37,43,63-
66].

There are a number of acceptable dosing regimens for azithromycin (table 3); these include the following:

● Five-day course

• 12 mg/kg (not to exceed 500 mg) on day 1, followed by 6 mg/kg (not to exceed 250 mg) on days 2
through 5 [36,43,63]

• 12 mg/kg (not to exceed 500 mg) on days 1 through 5 [2,64,66]

● Three-day course: 20 mg/kg (not to exceed 500 mg) on days 1 through 3 [37,65,66]

Data from studies in adults form the basis for the five-day course of 12 mg/kg on day 1 followed by 6 mg/kg
on days 2 through 5; data from studies in children form the basis for the five-day course of 12 mg/kg and the
three-day course of 20 mg/kg.

For the rare patient with an erythromycin-resistant strain of GAS who is unable to tolerate beta-lactam
agents, clindamycin is an appropriate choice [29,33,67]. (See "Allergy evaluation for immediate penicillin
allergy: Skin test-based diagnostic strategies and cross-reactivity with other beta-lactam antibiotics".)

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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 [68,69]. 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) [13,16,21].

Five days of therapy with cefpodoxime or cefdinir 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 [37,43,70-82]. Three injections of ceftriaxone on sequential days (or every other day) are
needed for optimal eradication.

Azithromycin may be administered as a five-day or three-day regimen [34-37,65,66]. (See 'Selection' above.)

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 [83-86].
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 [75,87-
90].

Antibiotics for other organisms — The differential diagnosis of acute pharyngitis is outlined separately
(table 4). (See "Evaluation of acute pharyngitis in adults".)

The approach to treatment of infection due to Streptococcus other than group A, influenza, infectious
mononucleosis, primary HIV infection, N. gonorrhoeae, Mycoplasma pneumoniae, Chlamydia 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 [91-93]. In general, we favor treatment for
pharyngitis only in the setting of a positive diagnostic test [43]. 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 [94,95]. 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 [95]. 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. Patients are considered no longer contagious after 24 hours of
antibiotic therapy [14]. Patients may return to daycare, school, camp, or work after 24 hours of antibiotics;
one study suggests children treated with amoxicillin for streptococcal pharyngitis by 5:00 pm may be
permitted to attend school the following day if afebrile and clinically improved [15].

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.)

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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 asymptomatic Streptococcus carriers
[96,97].

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 [97]
● 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 [98]. Repeat treatment should be administered with an agent with greater beta-lactamase stability than
the previous agent [58]. 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. First-generation cephalosporins
regimens include cephalexin and cefadroxil; second generation regimens include cefprozil, cefuroxime, and
cefaclor; third-generation cephalosporins include cefdinir, cefpodoxime, and cefixime. (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 [96,98,99]:

● 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 3). Repeat treatment should be administered with an agent with greater
beta-lactamase stability than the previous agent [58].

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 3) [58,67,100]. (See 'Carriers' below.)

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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 [101,102]. This was illustrated in a
randomized trial including 187 children with recurrent pharyngitis, of whom 95 were managed with
tonsillectomy [101]. The incidence of pharyngitis during the first two years of follow-up was significantly lower
among the tonsillectomy group. (See "Tonsillectomy and/or adenoidectomy in children: Indications and
contraindications", section on 'Recurrent throat infection'.)

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

PREVENTION

Carriers — In general, group A Streptococcus (GAS) resides in the oropharynx of Streptococcus carriers in
the absence of host immunologic response to the organism [103]. 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
[98]. 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 [103]. Moreover, eradication of GAS from the
upper respiratory tract of carriers is much more difficult than eradication of GAS from patients with acute
infection [52,96,104]. 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 [105-109], and foodborne transmission of GAS pharyngitis by asymptomatic food service workers
with nasopharyngeal carriage has been reported [108,110,111]. Factors that can reduce foodborne
transmission of GAS pharyngitis include thorough cooking, complete reheating, and use of gloves while
handling food [105,112].

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 "Acute
rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)'.)

Vaccination — There is no vaccine against GAS available for clinical use, although development of this
preventive measure is under investigation [113,114]. 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.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected
countries and regions around the world are provided separately. (See "Society guideline links: Streptococcal
tonsillopharyngitis".)

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-

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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 education: Sore throat in adults (The Basics)" and "Patient education: Strep
throat in children (The Basics)" and "Patient education: Scarlet fever (The Basics)")

● Beyond the Basics topics (see "Patient education: Sore throat in children (Beyond the Basics)" and
"Patient education: 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 3).
First-generation cephalosporins (such as cephalexin and cefadroxil) are acceptable alternatives 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.)

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● 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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GRAPHICS

Classification of streptococci commonly isolated from humans

Lancefield Hemolytic
Species Comments
antigen(s) reaction(s)

S. pyogenes A Beta Pyogenic; can be differentiated from beta-hemolytic anginosus

group strains with the group A antigen by the formation of
relatively large colonies and other phenotypic traits; agent of
pharyngitis and respiratory, skin, and other infections; can
cause nonsuppurative sequelae (acute rheumatic fever, acute
glomerulonephritis)

S. agalactiae B Beta, gamma Pyogenic; hemolytic reaction is weak; agent of

chorioamnionitis, puerperal sepsis, neonatal sepsis and
meningitis, and infections in nonpregnant adults

S. dysgalactiae C, G* Beta Pyogenic; formerly named S. equisimilis; can be differentiated

subsp. from beta-hemolytic S. anginosus group strains with the C or
equisimilis G antigen by the formation of relatively large colonies and
other phenotypic traits; agent of respiratory and deep tissue
infections, cellulitis, and septicemia

S. pneumoniae Not detected or Alpha S. pneumoniae, an agent of respiratory infections, otitis media
and the S. not useful for and meningitis, is a close relative of members of the S. mitis
mitis spp. differentiation spp. group, a viridans streptococcal group. The non-
group pneumococcal S. mitis spp. group members include S. mitis,
S. oralis, S. sanguinis, S. gordonii, and S. pseudopneumoniae.
Some non-pneumococcal species produce extracellular
polysaccharides ¶ and play roles in subacute bacterial
endocarditis and infections in neutropenic hosts.

S. anginosus A, C, F, G, or Alpha, beta, Viridans streptococcal group composed of three species: S.

spp. group no detectable gamma anginosus, S. constellatus, and S. intermedius; two
antigen subspecies of S. constellatus, S. constellatus subsp.
constellatus and S. constellatus subsp. pharyngis, have been
described; formerly known as S. milleri; beta-hemolytic
strains form small colonies compared with those of pyogenic
beta-hemolytic group A, C, and G streptococci and also differ
in other phenotypic traits; agents of purulent infections

S. bovis spp. D Alpha, gamma Viridans streptococcal group formerly known as group D
group nonenterococcal streptococci; species commonly isolated from
humans have been reclassified as S. gallolyticus subsp.
gallolyticus (formerly S. bovis biotype I), S. gallolyticus subsp.
pasteurianus (formerly S. bovis biotype II/2), S. infantarius
subsp. infantarius, and S. lutetiensis (formerly S. bovis
biotype II/1); some strains produce extracellular
polysaccharides; ¶ agents of endocarditis; isolated from blood
in patients with colonic cancer

S. mutans spp. Not useful for Alpha, gamma, Viridans streptococcal group; S. mutans and S. sobrinus spp.
group differentiation occasionally are commonly isolated from humans; produce extracellular
beta polysaccharides; ¶ agents of dental caries and endocarditis

S. salivarius Not useful for Alpha, gamma Viridans streptococcal group; S. salivarius and S. vestibularis
spp. group differentiation spp. commonly isolated from humans; strains in the S.
salivarius group may react with Lancefield group K antiserum
and may produce extracellular polysaccharieds;* infrequent
opportunists in compromised hosts

* Isolates with the group A antigen have also been described.

¶ Extracellular polysaccharides (dextran, levan) are thought to aid colonization and may play a role in virulence.

Reproduced from: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th ed, Bennett JE,
Dolin R, Blaser MJ (Eds), Saunders, Philadelphia 2014. Table used with the permission of Elsevier Inc. All rights reserved.

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Streptococci primarily isolated from animals that may occasionally cause human
infection

Lancefield Hemolytic
Species Comments
antigen(s) reaction

S. dysgalactiae C, L Alpha, beta, Pathogen of domesticated animals; participation in human

subsp. gamma infections not well documented
dysgalactiae

S. equi C Beta Agent of equine strangles; participation in human infections

subsp. equi not well documented

S. equi C Beta Agent of bovine mastitis and infection in other domesticated

subsp. animals; implicated in outbreaks of nephritis in humans
zooepidemicus

S. porcinus E, P, U, V Beta Swine are usual hosts; isolated from human female genital
tract; may cross react with commercially available group B
streptococcal grouping reagents

S. canis G Beta Dogs and other animals are usual hosts; documented as an
infrequent human pathogen

S. suis R, S, T Alpha, beta* Swine are usual hosts; isolated infrequently from cases of
human meningitis

S. iniae No detectable Beta Fish are usual hosts; isolated infrequently from cutaneous and
antigen systemic infection in humans

* Alpha-hemolytic on sheep blood agar, but some strains may be beta-hemolytic on horse blood agar.

Reproduced from: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th ed, Bennett JE,
Dolin R, Blaser MJ (Eds), Saunders, Philadelphia 2014. Table used with the permission of Elsevier Inc. All rights reserved.

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Treatment of pharyngitis due to group A Streptococcus

Adults Children and adolescents

Oral penicillin V* (phenoxymethyl penicillin)

500 mg two to three times daily for 10 days If ≤27 kg: 250 mg two to three times daily for 10 days
If >27 kg: 500 mg two to three times daily for 10 days

Amoxicillin ¶

500 mg twice daily for 10 days Δ 50 mg/kg per day orally (maximum 1000 mg per day)
for 10 days. May be administered once daily or in two or
three equally divided doses. Δ

Intramuscular penicillin, single dose

Penicillin G benzathine (Bicillin L-A) 1.2 million units ◊
If ≤27 kg: Penicillin G benzathine (Bicillin L-A) 600,000
units OR penicillin G benzathine-penicillin G procaine
(Bicillin C-R 900/300), administer 600,000
units benzathine component (ie, two-thirds of 1.2 million
unit premixed IM syringe). Bicillin C-R 900/300 consists
of benzathine penicillin G 900,000 units mixed with
procaine penicillin G 300,000 units.
If >27 kg: Penicillin G benzathine (Bicillin L-A) 1.2
million units ◊

Cephalexin ¶§

500 mg orally twice daily for 10 days 25 to 50 mg/kg per day orally in two equally divided
doses (maximum 1000 mg per day) for 10 days

For patients with potential severe hypersensitivity to beta-lactam antibiotics (eg, penicillin,
cephalosporins):

Azithromycin ¥

500 mg orally on day 1 followed by 250 mg orally 12 mg/kg/dose (maximum 500 mg/dose) orally on day 1
on days 2 through 5 followed by 6 mg/kg/dose (maximum 250 mg/dose)
orally on days 2 through 5

Clarithromycin ¥

250 mg orally twice daily for 10 days 7.5 mg/kg/dose (maximum 250 mg per dose) orally
twice daily for 10 days

Clindamycin

300 mg orally three times daily for 10 days If ≤70 kg: 7 mg/kg/dose (maximum 300 mg per dose)
orally three times daily for 10 days
If >70 kg: 300 mg orally three times daily for 10 days

* Oral penicillin V is the drug of choice for group A streptococcal pharyngitis.

¶ Dose alteration needed for severe renal insufficiency.
Δ Once-daily amoxicillin is recommended by the 2009 American Heart Association (AHA) guidelines. It is noninferior to
amoxicillin administered in multiple daily doses.
◊ Penicillin G benzathine-penicillin G procaine mixture (Bicillin C-R 900/300) is associated with less pain with injection
than penicillin G benzathine. However, it requires further study before routine use in adults or large adolescents is
acceptable.
§ Other cephalosporins are also acceptable (cefadroxil, cefprozil, cefaclor, cefuroxime, loracarbef, cefdinir, cefpodoxime,
cefixime, and ceftibuten). Cefpodoxime and cefdinir are US Food and Drug Administration (FDA) approved for 5 days of
therapy; all other cephalosporins require 10 days of therapy.
¥ There are a number of acceptable dosing regimens for azithromycin; these include five-day and three-day regimens
(refer to the UpToDate topic on treatment of streptococcal pharyngitis for additional discussion). The azithromycin doses
in the table are those provided by the Infectious Diseases Society of America (IDSA). The adult azithromycin dose
provided by the AHA consists of 12 mg/kg/dose (maximum 500 mg/dose) orally once daily for five days; the pediatric
azithromycin dose provided by the AHA and American Academy of Pediatrics (AAP) consists of 12 mg/kg/dose (maximum
500 mg/dose) orally once daily for five days. Limited data are available for a three-day regimen (pediatric dose 20
mg/kg/dose [maximum 500 mg/dose] orally once daily for three days; adult dose 500 mg orally once daily for three
days). Erythromycin is an acceptable alternative to azithromycin.

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Data from:
1. 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. Circulation 2009; 119:1541.
2. American Academy of Pediatrics. Group A Streptococcal Infections. In: Red Book: 2015 Report of the Committee
on Infectious Diseases, 30th, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of
Pediatrics, Elk Grove Village, IL 2015. p.732.
3. 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. The IDSA has published an erratum to this publication, which clarifies the dose of azithromycin:
http://cid.oxfordjournals.org/content/58/10/1496.1.full.
4. Cohen R, Reinert P, De La Rocque F, et al. Comparison of two dosages of azithromycin for three days versus
penicillin V for ten days in acute group A streptococcal tonsillopharyngitis. Pediatr Infect Dis J 2002; 21:297.

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Causes of acute pharyngitis

Estimated frequency,
Examples
percent

Common bacterial pathogens 15 Group A streptococci

Group C streptococci

Group G streptococci

Less common bacterial <5 Chlamydophila pneumoniae

pathogens (TWAR)

Mycoplasma pneumoniae

Arcanobacterium haemolyticum

Corynebactrium diphtheriae

Fusobacterium necrophorum

Neisseria gonorrheae

Treponema pallidum

Francisella tularensis

Viruses 50 Rhinovirus

Adenovirus

Influenza A and B

Parainfluenza

Coxsackievirus

Coronavirus

Echovirus

Herpes simplex virus

Epstein Barr virus

Human immunodeficiency virus

Cytomegalovirus

Respiratory syncytial virus

Metapneumovirus

No pathogen isolated 30

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