CM E
Pharyngitis and
Streptococcal Throat Infections
Judith M. Martin, MD
CM E EDUCATIONAL OBJECTIVES
1. Identify the major clinical mani-
festations of group A streptococ-
cal pharyngitis.
2. Review the available clinical labo-
ratory tests for diagnosis of group
A streptococcal infections.
3. Discuss the most appropriate treat-
ment for group A streptococcal
infections, including the drug(s) of
choice, alternative therapies, duration
of therapy, and ineffective agents.
Judith M. Martin, MD, is Associate Pro-
fessor of Pediatrics, University of Pitts-
burgh School of Medicine, Division of
Infectious Disease.
Address correspondence to: Judith M.
Martin, MD, Childrens Hospital of Pitts-
burgh of UPMC, Division of Infectious
Disease, One Childrens Hospital Drive,
4401 Penn Ave., AOB Suite 3200, Pitts-
burgh, PA 15224; fax: 412-692-7016. e-
mail: judy.martin@chp.edu.
Dr. Martin has disclosed no relevant fi-
nancial relationships.
doi: 10.3928/00904481-20091222-02
22 | www.PediatricSuperSite.com
3901Martin.indd 22
P
haryngitis is the term used to
describe any inflammation of
the pharynx. Sore throat is a
very common complaint for which
children and adolescents seek medical
care. Pharyngitis is primarily caused by
bacteria and viruses. When evaluating
a patient with a sore throat, it is impor-
tant to differentiate pharyngitis caused
by group A streptococcus (GAS) from
that caused by other pathogens. GAS is
the most common cause of pharyngitis
that is treatable with antibiotics. During
the winter, approximately 15% to 25%
of all cases of pharyngitis in children
will be caused by streptococcal infec-
tion.1 In adults, this number is closer to
10%.2 It is important to identify cases
of GAS pharyngitis because antibiotic
treatment leads to a more rapid clini-
cal cure and decreases transmission
of GAS to others. Treatment of GAS
pharyngitis can also prevent suppura-
tive and some non-suppurative compli-
cations. The suppurative complications
are those that occur shortly after the
initial infection (without any latency
PEDIATRIC ANNALS 39:1 | JANUARY 2010
1/6/2010 2:40:57 PM

period) and include peritonsillar and
retropharyngeal abscesses, acute otitis
media, cervical adenitis, and acute bac-
terial sinusitis. Nonsuppurative com-
plications occur after a latency period
of a few weeks and include poststrep-
tococcal glomerulonephritis and acute
rheumatic fever (ARF). In adults, the
importance of treating to prevent non-
suppurative complications is less ur-
gent. One exception is in the military or
in college dormitories where outbreaks
of ARF have been reported.
DIFFERENTIAL DIAGNOSIS
Most immunocompetent children
and adolescents who present with a sore
PEDIATRIC ANNALS 39:1 | JANUARY 2010
3901Martin.indd 23
CM E
throat have pharyngitis, which is pri-
marily caused by bacteria and viruses.
Bacterial etiologies of pharyngitis in-
clude Streptococcus pyogenes (or group
A streptococcus), as well as Corynebac-
terium diphtheriae, Arcanobacterium
haemolyticum, Neisseria gonorrheae,
group C and group G streptococci and
Mycoplasma pneumoniae. Viruses that
cause pharyngitis include Epstein-Barr
virus (EBV), herpes simplex virus
(HSV), adenovirus, enterovirus, hu-
man immunodeficiency virus (HIV),
cytomegalovirus (CMV), influenza,
and parainfluenza viruses. Pharyngitis
caused by viruses is very often associ-
ated with upper respiratory symptoms,
iStockphoto.com
such as rhinorrhea, nasal congestion,
and cough. Patients with pharyngitis
caused by GAS almost always do not
have cough or nasal symptoms.
Infections in the peripharyngeal area
tend to occur in the fascial space and
lymph nodes and may lead to a com-
plaint of a sore throat. Examples of these
types of infections include peritonsillar
abscess, parapharyngeal, retropharyn-
geal or prevertebral space infections. In
addition to a sore throat, the patient may
also have trismus or pain with swallow-
ing and eating. These patients may pres-
ent with fever and other signs of system-
ic toxicity. Stridor, airway obstruction or
drooling may also occur in patients with
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1/6/2010 2:40:57 PM

significant swelling of the tonsillar and
peritonsillar areas. On physical examina-
tion, there may be swelling of the face
and neck, with or without erythema of
the overlying skin. When the orophar-
ynx is examined, there may be pooling
of secretions in the mouth or asymmetry
of the tonsils or pharynx. Complications
of these infections include suppurative
jugular thrombophlebitis, or Lemierres
syndrome, which can be life threatening.
BACTERIAL CAUSES OF
PHARYNGITIS: GROUP A
STREPTOCOCCUS
GAS as a cause of pharyngitis is most
commonly observed in children aged 5 to
15 years. GAS appears in late winter and
early spring in temperate climates. It is
easily spread in classrooms and between
family members. Transmission is by in-
halation of large droplets or direct con-
tact with respiratory secretions. The in-
cubation period is 2 to 5 days. Untreated
patients are most contagious while they
are acutely ill; however, they may remain
infectious for approximately 2 weeks.
School-age children may develop
one to three streptococcal infections
each respiratory season.3 Some of
these infections are associated with
symptoms, whereas others are asymp-
tomatic or have atypical symptoms,
such as nasal discharge or conges-
tion accompanied by a sore throat.
One longitudinal study showed that
two-thirds of streptococcal infections
were not associated with recognizable
respiratory symptoms. Some children
develop numerous infections per year.
CLINICAL MANIFESTATIONS OF GAS
GAS pharyngitis commonly presents
with the abrupt onset of sore throat asso-
ciated with headache, fever, malaise, and,
occasionally, abdominal pain. The throat
pain often leads to decreased oral intake.
This is in contrast to the typical presenta-
tion of viral pharyngitis, which is usually
associated with upper respiratory symp-
24 | www.PediatricSuperSite.com
3901Martin.indd 24
CM E
toms, such as rhinorrhea, nasal conges-
tion, conjunctivitis, and cough. Clinical
examination alone cannot differentiate
pharyngitis caused by GAS from other
causes, unless a specific syndrome, such
as scarlet fever, is present. A combination
of typical clinical symptoms and signs on
physical examination may be highly sug-
gestive of GAS; however, only a minority
certain if cellular invasion is a necessary
Some children develop
numerous infections per year.
of episodes have all of the classic features.
The tonsils and pharynx may appear ery-
thematous, and an exudate is seen in 25%
of cases. Approximately 50% of children
with GAS pharyngitis also have tender
anterior cervical lymph nodes on physical
examination. GAS is also more likely to
be the cause of pharyngitis for children 5
to 15 years who present between Novem-
ber and May in temperate climates. Many
studies have shown that scoring systems
are useful in predicting the likelihood
of streptococcal infection.2,4-6 However,
laboratory confirmation is essential in
making a precise diagnosis because phy-
sicians often overestimate the probability
that GAS is the cause of pharyngitis.5
PATHOGENESIS
Group A streptococci are gram-posi-
tive cocci that can be divided into more
than 100 M-serotypes or M-types based
on the M protein. Their virulence is direct-
ly related to the M protein on the cell sur-
face that inhibits phagocytosis. Although
GAS is thought of as a pathogen, it can
be part of the normal flora of the pharynx
and skin. In the throat, colonization ap-
pears to be caused by fibronectin-binding
proteins. Adherence to pharyngeal epithe-
lial cells can lead to pharyngitis. It is not
step in the pathogenesis of pharyngeal in-
fection. Streptococcus pyogenes can also
elaborate exotoxins, which are respon-
sible for the rash that is seen in patients
with the clinical syndrome of scarlet fe-
ver. The originally described exotoxins
were types A, B, and C. More recently,
additional pyrogenic extoxins have been
discovered. The toxin is produced at the
site of infection and then enters the circu-
lation to exert its effect.
BACTERIAL CAUSES OF
PHARYNGITIS OTHER THAN
GROUP A STREPTOCOCCUS
A. haemolyticum is not a common
cause of pharyngitis and is difficult to
identify on a standard throat culture.
The organism grows slowly and is often
only observed after 72 hours of incuba-
tion. Clinical symptoms may include
fever, an exudative pharyngitis and a
rash that is pruritic and may appear to
be scarlatiniform. Clinical symptoms
will improve without any specific anti-
biotic therapy, although erythromycin is
the drug of choice when the infection is
recognized.
N. gonorrheae as a cause of pharyngi-
tis can be seen in adolescents and adults
who engage in oral-genital sex. There
are no distinguishing findings on physi-
cal examination. Selective media must
be used to isolate this organism from a
throat swab. Specific therapy with ceftri-
axone is needed to prevent disseminated
disease and further transmission.
Group C and group G streptococci can
cause pharyngitis in children and adults.
Group C and group G streptococci have
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been shown to cause post-streptococcal
glomerulonephritis. Often, the presence
of these organisms is not reported by
laboratories when evaluating a standard
throat culture. Antibiotic therapy is not
necessary for a clinical cure, nor is it
known to prevent glomerulonephritis.
Cornyne diphtheriae is extremely rare
in the Northern Hemisphere. Epidemic
disease has been documented in the for-
mer Soviet Union and in parts of Asia,
Africa, and the Middle East. Patients of-
ten have gradual onset of sore throat. It
can be distinguished from other causes
of pharyngitis on physical exam because
it produces a characteristic membrane
in the pharynx. Attempts to remove this
membrane can lead to bleeding. A speci-
men obtained from beneath the mem-
brane or a piece of the membrane can
be sent for culture. Selective media are
needed for isolation of this bacterium.
The laboratory should be notified if
diphtheria is the suspected diagnosis.
M. pneumoniae can cause an acute
bronchitis or an upper respiratory ill-
ness associated with a sore throat.
These patients often present with fe-
ver, malaise, nonproductive cough, and
headache. This is most commonly seen
in previously healthy school-aged chil-
dren and adolescents. Clinical symp-
toms will improve without any specific
antibiotic therapy.
VIRAL CAUSES OF PHARYNGITIS
Infectious mononucleosis is usually
caused by EBV. The most commonly rec-
ognized clinical syndrome consists of fe-
ver, severe pharyngitis, posterior and an-
terior cervical adenopathy, and prominent
constitutional symptoms, such as fatigue.
The illness occurs most often in adoles-
cents and usually lasts much longer than
the typical course expected with strepto-
coccal pharyngitis. Younger children can
also have EBV infection; however, their
clinical illness is likely to be mild and
may manifest as an uncomplicated viral
upper respiratory tract infection.
PEDIATRIC ANNALS 39:1 | JANUARY 2010
3901Martin.indd 25
CM E
Primary HIV infection can occur days
to weeks after sexual or blood exposure
of an infected individual. Clinical features
may include fever, pharyngitis, adenopa-
thy, rash, and an enlarged spleen. This
diagnosis should be suspected in patients
with a history of possible exposure.
Influenza is common in epidemic
form at specific times of the year. Symp-
toms often include the abrupt onset of
sore throat with high fever and myalgias.
Virus isolation and polymerase chain re-
action (PCR) tests are available to con-
firm this diagnosis. Rapid diagnostic
tests are specific but not very sensitive
and are not preferred for diagnosis. An-
tivirals are available for treatment.
HSV can lead to symptoms of a sore
throat, especially in adolescents and
young adults. It is often accompanied by
an exudative or ulcerative pharyngitis,
which is painful and leads to significantly
decreased oral intake. Tender cervical ad-
enopathy can be appreciated on examina-
tion. Because it is treatable with acyclovir
or its cogeners, the diagnosis should be
considered in sexually active patients. Vi-
ral culture is definitive.
Adenovirus can cause a variety of
clinical symptoms and is most commonly
seen in the late winter, spring, and early
summer. It should be considered if the pa-
tient presents with pharyngitis and bilat-
eral conjunctivitis, especially if it is hem-
orrhagic (pharyngoconjunctival fever).
Enteroviruses, especially the cox-
sackieviruses, can manifest as pharyn-
gitis, herpangina, stomatitis, and fever.
Small vesicles can be seen in the poste-
rior pharynx. The young child may also
have lesions on the hands and feet (hand-
foot-and-mouth disease). In temperate
climates, these infections are seen during
the summer months and early fall.
CMV can cause an acute infection and is
most commonly transmitted by respiratory
droplets. In an immunocompetent host, the
infection is often asymptomatic. However,
some patients may have a mononucleosis-
like syndrome with mild pharyngitis.
DIAGNOSIS
Many clinicians use one of several
rapid diagnostic tests to identify the
presence of GAS in the pharynx. These
tests, which are primarily based on ex-
traction and identification of the group A
carbohydrate antigen, yield results that
demonstrate high specificity but vari-
able sensitivity when compared with the
standard throat culture.7,8 Accordingly, it
is recommended that a throat culture be
performed for any patient with a nega-
tive rapid antigen test in whom GAS
pharyngitis is suspected.9-11
For children or adults who are tested
and found to be negative for GAS, the
most likely etiology is a viral infection
that usually resolves spontaneously. In
most circumstances, unless ulcerations
are seen on examination, viral cultures
of the pharynx are not helpful. How-
ever, if symptoms persist or if there are
other indications in the exam or history
that raise suspicion for one of the other
causes listed, then other diagnostic test-
ing should be considered.
Several clinical presentations should
prompt consideration for additional di-
agnostic testing.
1. Unusually severe symptoms asso-
ciated with difficulty swallowing, drool-
ing, hot potato voice, significant neck
swelling, or an asymmetrical appearance
of the tonsils or pharynx should prompt
consideration for the possibility of a
parapharyngeal space infection, retro-
pharyngeal space infection (in younger
children), or peritonsillar abscess. A
plain radiograph may demonstrate soft
tissue swelling; however, most patients
require a contrast enhanced computed
axial tomography (CT) scan, which can
further define the anatomy. Magnetic
resonance image (MRI) may also be
useful for further evaluation of possible
vascular involvement.
2. A history of oral-genital sexual
contact in a patient with severe pharyn-
gitis suggests the possibility of gonococ-
cal infection. The laboratory requisition
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 CM E
TABLE.
Recommended Therapy for the
Treatment of GAS Pharyngitis
Antimicrobial Agent Dose
Penicillin VK < 27 kg: 250 mg two to three times per day for 10 days
> 27 kg: 500 mg two to three times per day for 10 days
Penicillin G benzathine < 27 kg: Single dose of 600,000 units IM
> 27 kg: Single dose of 1.2 million units IM
Amoxicillin 50 mg/kg once a day (maximum 1000 mg per day) for 10 days
Erythromycin estolate 20-40 mg/kg/day for 10 days
Erythromycin
40 mg/kg/day, in 2 to 4 divided doses for 10 days
ethylsuccinate
Cephalexin 30 mg/day, in four divided doses for 10 days
Cefadroxil 30 mg/day, in two divided doses for 10 days
Azithromycin 12 mg/kg/day once daily for 5 days
must request culture for N. gonorrhoeae only for these patients. Some physi-
because the swab must be plated on se- cians begin antimicrobial therapy pend-
lective media. ing culture results and discontinue the
3. Persistent or severe sore throat with treatment if the throat culture is nega-
significant constitutional symptoms sug- tive. However, it is preferred to wait to
gests possible EBV infection. It is ap- initiate treatment until testing results
propriate to order a complete blood count confirm the presence of GAS. Treat-
with differential, monospot testing and/or ment within 9 days of the onset of ill-
EBV serologies. If there is also a history ness is effective in preventing ARF.12
of risky sexual behaviors, consider HIV Most physicians offices have rapid
RNA viral load or HIV DNA PCR to as- streptococcal antigen testing available,
sess for primary HIV infection. and most patients will be diagnosed im-
4. Vesicular lesions on oral-labial mediately.
margins or ulcerative lesions of the phar- Treatment of GAS pharyngitis leads
ynx suggest HSV, especially when there to a more rapid clinical cure and de-
is a history of oral-genital contact. A vi- creases transmission of GAS to other
ral culture or direct antigen for HSV is children. Treatment of GAS pharyngitis
appropriate. is effective in preventing ARF; however
5. Pharyngitis with abrupt onset, high it does not prevent the development of
fever, and myalgias during influenza sea- poststreptococcal glomerulonephritis.
son should prompt testing for influenza A. Because of the general increase in rates
of resistance to antibiotics, antimicro-
ANTIBIOTIC THERAPY bial therapy should be prescribed only
Either a positive rapid streptococ- for proven episodes of GAS pharyngi-
cal antigen test or a throat culture that tis. Furthermore, many experts support
is positive for S. pyogenes confirms a the idea of being selective in perform-
diagnosis of streptococcal pharyngitis ing diagnostic tests so as to avoid iden-
in the presence of appropriate clinical tifying GAS carriers rather than acutely
features. Antibiotics should be initiated infected youngsters.9-11
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3901Martin.indd 26
A clinical response in the symptoms
of streptococcal infection is usually
achieved within 24 to 48 hours after ini-
tiation of therapy. However, even with-
out treatment, fever and symptoms re-
solve within 3 to 4 days of the onset of
illness. Accordingly, the persistence of
symptoms beyond this time period sug-
gests either the development of a sup-
purative complication or that the child
may be a carrier of GAS (rather than
acutely infected), with the presenting
symptoms attributable to an alternate
cause of pharyngitis.
Penicillin remains the drug of choice
for the treatment of GAS pharyngitis.
Penicillins efficacy in preventing rheu-
matic fever is well established. Other
desirable features of penicillin include
low cost, a low incidence of side ef-
fects, and a narrow antimicrobial spec-
trum. There has been no documenta-
tion of resistance in GAS to penicillin.
Recommended therapeutic options for
the treatment for GAS pharyngitis are
shown in the Table. Penicillin V potas-
sium is traditionally given three to four
times a day. However, a study conduct-
ed by Gerber demonstrated that twice-
daily dosing of penicillin was as effec-
tive as three-times-per-day dosing.13
Treatment with penicillin should be
continued for 10 days because shorter
courses have shown decreased efficacy.
The use of a single dose of intramuscu-
lar penicillin G benzathine is as effec-
tive as oral penicillin and was the long-
time gold standard in the treatment of
GAS pharyngitis. The slow release for-
mulation can provide bactericidal levels
against GAS for as long as 28 days, en-
suring adequate serum levels of antibi-
otic. Benzathine penicillin is preferred
for those patients who are unlikely to
complete a full 10-day course of oral
therapy (see the Table for doses).
Amoxicillin has been shown to be
as effective as penicillin in eradicating
GAS, is more palatable, and provides
easier dosing. Because many children
PEDIATRIC ANNALS 39:1 | JANUARY 2010
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cannot take pills or capsules, amoxicil-
lin suspension is a common substitution
for penicillin. Most clinicians prescribe
amoxicillin two or three times daily. Re-
cent clinical studies have demonstrated
once daily dosing with 50 mg/kg of
amoxicillin (maximum dose 1,000 mg)
for a 10-day course to be effective for
GAS pharyngitis;14-17 this schedule has
been endorsed by the Committee on In-
fectious Disease of the American Acad-
emy of Pediatrics (AAP).10,11
Erythromycin remains the first alter-
native choice in patients who are aller-
gic to penicillin or amoxicillin. It has
been shown to be as effective as peni-
cillin in eradicating macrolide-sensitive
GAS from the pharynx. However, doc-
umented reports of erythromycin-resis-
tant GAS have occurred in Finland, Ja-
pan, Greece, and, most recently, in the
United States.18-21 Although previous
studies from the United States reported
low rates of GAS isolates that were re-
sistant to macrolides, more recent in-
vestigations have documented a broad
range of rates of resistance. Physicians
should take into consideration the re-
sistance rates in their community when
prescribing this class of antibiotics. Two
of the newer macrolides, azithromycin
and clarithromycin, are commonly used
instead of erythromycin because they
are only given once or twice a day. For
the patient who has an infection with a
macrolide-resistant strain of GAS and
cannot tolerate beta-lactam antibiotics,
clindamycin is a reasonable alternative.
However, clinicians should be aware
of the potential presence of inducible
clindamycin resistance in some strains
of macrolide-resistant GAS.18
Oral cephalosporins have been stud-
ied extensively in the treatment of GAS
pharyngitis and are highly effective.
Some studies have reported higher bac-
teriologic cure rates when treatment is
undertaken with cephalosporins, com-
PEDIATRIC ANNALS 39:1 | JANUARY 2010
3901Martin.indd 27
CM E
pared with the penicillins.22 Other
authors have not supported this con-
clusion, suggesting that the observed
differences may be attributable to the
inclusion of GAS carriers in these stud-
ies and a greater ability of cephalospo-
rins to eradicate the carrier state com-
pared with penicillin. Although there
are some advantages to the cephalo-
sporins, it is important to note that, as
a class, they are more expensive than
penicillin, are associated with greater
side effects, and have a broader spec-
trum of activity. Their routine use can-
not be endorsed at this time.
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