++
Streptococcus pyogenes is highly communicable.
Respiratory droplet spread is the major route for transmission of
strains associated with upper respiratory tract infection, although
skin-to-skin spread is known to occur with strains associated with
pyoderma. Foodborne outbreaks are not rare and often are associated
with egg-containing foods. Although uncommon, nursery outbreaks of
group A streptococcal infections have been reported. The incidence
of pharyngeal infection with group A streptococci is highest in
children ages 5 to15 years. Indeed, group A streptococcal pharyngitis
has been described as an “occupational disease” of
school aged children. Streptococcus pyogenes also
has the potential to produce outbreaks of disease in younger children in
group daycare. In temperate zones, pharyngeal infection is most
common during late autumn, winter, and early spring. Group A streptococcal
skin infections occur most frequently during the summer in temperate
climates but can occur year round in warmer climates.
+++
Clinical Manifestations
+++
Streptococcal
Pharyngitis
++
Acute pharyngitis represents one of the most common reasons children
are seen by primary care physicians. Yet, in spite of the common nature
of the infection, the diagnostic and therapeutic approach to the
child with pharyngitis or tonsillitis remains a source of controversy.5-7 Some
of the points debated among clinicians include the following: (1) Which children should
be tested for streptococcal pharyngitis? (2) How should
children be tested for streptococcal pharyngitis? (3) Whatantibiotic
therapeutic approach(s) should be used for streptococcal
pharyngitis?
++
In general, decisions about laboratory testing and antibiotic
therapy should be made only after careful consideration of clinical
findings and epidemiologic considerations. The most important historical
information in the evaluation of the complaint of sore throat is
that of the presence or absence of other symptoms of upper respiratory infection.
Children with bona fide streptococcal pharyngitis rarely
if ever have cough, rhinorrhea, or symptoms of a viral
upper respiratory infection (URI), and the diagnosis of streptococcal pharyngitis
can almost always be excluded with the clinical findings of coryza,
hoarseness, cough, or conjunctivitis. Although these are important
exclusionary criteria, the pediatrician must be aware that the signs
and symptoms of streptococcal pharyngitis may be nonspecific and
vary greatly depending on the age of the patient, the severity of
the infection, or the seasonal timing of the illness. Young infants
do not present with classic signs and symptoms of pharyngitis. Streptococcal
upper respiratory tract infections in infants and toddlers may instead
be characterized by low grade fever, anorexia, and a serous
nasal discharge (so-called streptococcosis). Conversely, some patients
may be toxic, with high fever, malaise, headache, and severe pain
on swallowing. Vomiting and abdominal pain may be prominent early
symptoms, simulating gastroenteritis or even acute appendicitis.
++
On physical examination, children with group A streptococcal
pharyngitis classically demonstrate tonsillopharyngeal erythema,
a red edematous uvula, palatal petechiae, and tender anterior cervical
adenitis. Typically, tonsils are enlarged and erythematous with
patchy exudate on the surface. The papillae of the tongue may be
red and swollen (so-called strawberry tongue). Cutaneous petechiae
have even been noted, and a scarlatiniform rash may be present
(Fig. 285-1). When the characteristic rash of
scarlet fever is present, a clinical diagnosis can be made with
increased confidence. However, it is difficult to consistently make
the diagnosis of streptococcal pharyngitis on clinical grounds alone.
Therefore, even the most experienced clinician should consider bacteriologic
confirmation of the diagnosis whenever possible. Obtaining appropriate
diagnostic testing for group A streptococcal pharyngitis before
therapy is instituted may prevent unnecessary antibiotic prescriptions
for viral pharyngitis.8
++
++
What kind of bacteriologic confirmation of the tentative diagnosis
of streptococcal pharyngitis is appropriate? If performed correctly,
a throat swab cultured on a blood agar plate has a sensitivity of
90% to 95% in detecting the presence of S
pyogenes in the pharynx. The specimen should be obtained
from the surface of both tonsils/tonsillar fossae and from
the posterior pharyngeal wall. Concern has been expressed regarding
the delay of 24 to 48 hours required for bacteriologic culture,
and clinicians often feel pressure to initiate therapy immediately,
prior to obtaining culture results. Since treatment of streptococcal
sore throat as long as 9 days after onset of symptoms is still effective
in preventing rheumatic fever, initiation of antibiotics is rarely
of urgent importance. Early antibiotic therapy may have beneficial
effects in relieving symptoms and allowing an earlier return to
school or daycare, but may have disadvantages. Some studies suggest
that children receiving immediate antibiotic therapy are more likely
to have symptomatic recurrences in the months following treatment
than are children who delay the initiation of therapy by 48 hours.
Delaying antibiotics may allow for an immune response to occur that
protects the child against reinfection. These questions continue
to be sources of controversy in the management of streptococcal
pharyngitis.9-11
++
When the diagnosis of streptococcal pharyngitis seems particularly
likely based on clinical findings, or an immediate decision about
antibiotic therapy is required, the use of rapid antigen detection
tests can be of value in confirming the diagnosis. Most rapid antigen
detection kits use antibody for detection of the group A carbohydrate
antigen in the cell wall. The specificity of these antibody tests
is superior to their sensitivity. Currently available rapid streptococcal
tests have a sensitivity of 70% to 90% compared
with standard throat cultures. The sensitivity may depend on the
inoculum obtained in the clinical sample: The sensitivity may be
no greater than 75% for colonization (or light growth on
culture) to approximately 95% in symptomatic pharyngitis (where
culture usually reveals a heavy growth). When clinical suspicion
or concern is high, a negative result with the rapid strep test
should be confirmed by throat culture. When identified by culture,
group A streptococcus does not require antibiotic susceptibility
testing.12
++
When a fine, diffuse erythematous rash (Fig. 285-1)
is present in the setting of acute streptococcal pharyngitis, the
illness is called scarlet fever. The modes of streptococcal transmission, age
distribution, and other epidemiologic features are identical to
those for streptococcal pharyngitis. The rash is caused by the pyrogenic exotoxins,
SPE A, B, C, and F. It often is noticed initially on the neck and
upper chest. It is a diffuse, finely papular, erythematous eruption producing
a bright red discoloration of the skin, which blanches on pressure.
The texture is that of fine sandpaper. The flexor skin creases, particularly
in the antecubital fossae, and the groin area may be unusually prominent
(Pastia’s lines). The circumoral skin is pale, giving the
appearance of pallor. Small vesicular lesions (miliary sudamina)
may appear on the abdomen, hands, and feet. Toward the end of the
first week of illness, the rash fades, followed by desquamation
over the trunk which progresses to the hands and feet. Scarlet fever
may be confused with roseola, Kawasaki disease, drug eruptions,
and toxin-mediated Staphylococcusaureus infections.
+++
Streptococcal
Skin Infections
++
The most common form of skin infection due to group A streptococcus
is superficial pyoderma. Also referred to as streptococcal
impetigo (or impetigo contagiosa), it occurs commonly in tropical
climates, but can be highly prevalent in temperate climates as well,
particularly during the summer months. Major risk factors that predispose
to this infection include local injury to skin caused by insect
bites, scabies, atopic dermatitis, and minor trauma. This form of
streptococcal infection is usually painless and the patient is usually
afebrile. Streptococcal impetigo usually has the highest incidence
in young children (ages 2–5 years). Streptococcal impetigo
usually appears first as a discrete papulovesicular lesion surrounded
by a localized area of redness. The vesicles rapidly become purulent
and then crusted, in contrast to the classic bullous appearance
of impetigo resulting from S aureus. Lesions are most
commonly encountered on the face and extremities. If untreated,
streptococcal impetigo is usually a mild but chronic illness, often
spreading to other parts of the body. Regional lymphadenitis may
be observed. Pyoderma-associated group A strains such as M/emm 49,
M/emm 55, and M/emm 57
are associated with poststreptococcal glomerulonephritis. The M/emm types
that give rise to streptococcal tonsillitis (eg, types 1, 3, 4,
5, 6, 12) uncommonly cause streptococcal impetigo.
++
Deeper soft tissue infections may occur as the result of S
pyogenes. A deeply ulcerated form of streptococcal impetigo,
ecthyma, may complicate streptococcal impetigo. This form of infection tends
to involve deeper layers of the skin and is encountered mainly in
the tropics. Streptococcal cellulitis is an acute, rapidly spreading
infection of skin and subcutaneous tissue that can follow burns,
wounds, surgical incisions, varicella infection, and mild trauma.
In contrast to impetigo, pain, tenderness, swelling and erythema,
and systemic toxicity are common, and patients may have associated
bacteremia. Prompt antibiotic therapy and careful serial examination
are crucial, as cellulitis may progress to necrotizing fasciitis. Perianal
cellulitis and vaginitis should be considered in children who complain
of perineal discomfort or vaginal discharge. Erysipelas is now a
relatively rare acute streptococcal infection involving the deeper
layers of the skin and the underlying connective tissue. The face
is a commonly involved site, especially in adults. The skin over
the affected area is swollen, red, and very tender, and superficial
blebs may be present. The most characteristic finding in erysipelas
is the sharply defined, slightly elevated border, in contrast to
the indistinct border of streptococcal cellulitis. Cultures obtained
by leading edge needle aspiration of inflamed areas will often result
in a positive culture.
+++
Necrotizing
Fasciitis
++
Necrotizing fasciitis resulting from S pyogenes (so-called
streptococcal gangrene) is an acute, rapidly progressive, severe
deep infection of the fascia and subcutaneous tissues and is associated
with extensive destruction of superficial and deep fascia. Recent
varicella infection has proven to be an important risk factor for
necrotizing fasciitis, although routine childhood immunization against
chickenpox has had an impact on the incidence of this complication.13 The
onset is heralded by diffuse erythematous swelling, with exquisite pain
at the affected site that typically seems incompatible with the
degree of swelling noted by the clinician. As the lesion progresses,
often quite rapidly, the skin becomes bluish gray. It is not uncommon
for large hemorrhagic bullae to appear over the area. The area of involvement
under the skin is usually much larger than seems evident from the
superficial examination of skin. Compartment syndromes often occur.
Repeated surgical debridement of necrotic tissue is crucial. Differentiating
streptococcal cellulitis from necrotizing fasciitis can be difficult;
therefore, careful frequent serial physical examinations are crucial.
Surgical consultation early in the course of infection is essential.
+++
Streptococcal
Toxic Shock Syndrome
++
Streptococcal toxic shock syndrome (TSS) is characterized by
hypotension and multiple organ failure.14 Criteria
proposed by a CDC Working Group on Severe Streptococcal Infections
for the diagnosis of streptococcal toxic shock are outlined in Table 285-1. There is considerable overlap
with streptococcal necrotizing fasciitis; most cases occur in association with
soft tissue infections. However, streptococcal TSS may occur in
association with other focal streptococcal infections, including pharyngeal
infection. Renal impairment occurs in approximately 80% of
patients, and hepatic dysfunction occurs in 65%. ARDS is often
present in severe cases and should be looked for. The pathogenesis
of streptococcal toxic shock syndrome appears to be related in part
to the ability of certain SPEs (A, C, and F) to function as superantigens.
++
+++
Other Suppurative
Complications
++
Suppurative complications resulting from the spread of streptococci
to adjacent structures are occasionally observed. Cervical adenitis,
peritonsillar abscess, retropharyngeal abscess, otitis media, mastoiditis,
and sinusitis occur in children in whom the primary
illness has gone unnoticed or in whom treatment of the pharyngitis
has been incomplete. S pyogenes may cause pneumonia,
parapneumonic effusion, and epiglottitis. Group A streptococcus
is a common etiology of acute hematogenous osteomyelitis. Isolated
bacteremia, meningitis, and endocarditis have been described, but
these are relatively rare manifestations of group A streptococcal
infection.
+++
Post-Infectious
Complications of Group a Streptococcus Infection
++
Acute rheumatic fever is
discussed in detail in Chapter 235, where the Jones criteria for
diagnosis are detailed. Only 25% to 40% ARF patients
have a positive throat culture at the time of presentation. The
most reliable evidence of an antecedent group A streptococcal infection is
often identification of a serologic response to the organism.19
++
Glomerulonephritis can follow group A streptococcal infections
of either the pharynx or the skin. Its occurrence requires the presence of so-called
nephritogenic strains of group A streptococci in the community.
Type 12 is one of the most common M/emm serotypes
causing post-streptococcal glomerulonephritis after pharyngitis,
and M/emm type 49 is a type commonly related
to pyoderma-associated nephritis. The latent period between the
group A streptococcal infection and the onset of glomerulonephritis
varies from 1 to 2 weeks after streptococcal pharyngitis, but is
approximately 21 days after pyoderma. Like ARF, the pathogenesis
of PSGN appears to be immunologically mediated (see Chapter 472).
++
Sydenham chorea is the most common cause of acquired chorea in
children and occurs most commonly between ages 5 and 15 years. It
is a cardinal feature of rheumatic fever and is sufficient alone
to make a diagnosis. SCH usually occurs several weeks to months after
untreated streptococcal infection (beta hemolytic streptococcus)
(see Chapter 566). In 1998 a syndrome known
as pediatric autoimmune neuropsychiatric disease associated with streptococci
(PANDAS) was described. Patients are usually prepubertal children
who develop multiple neuropsychiatric symptoms (tics and obsessive-compulsive
behavior), and it was suggested that this was temporally related
to group A streptococcal infection. Whether or not this syndrome
is related to streptococcal infection remains unconfirmed. There
is no evidence from controlled studies to support the efficacy of
continuous or suppressive antimicrobial therapy for these children.
(See Chapter 566.)
++
Treatment approaches for group A streptococcal infections vary
depending on the clinical syndrome. Worldwide, penicillin remains
the most widely used therapy. Remarkably, no penicillin-resistant
clinical isolates of S pyogenes have ever been
encountered. Penicillin therefore remains a drug of choice (except
in penicillin allergic individuals) for pharyngeal infections
as well as for complicated or invasive infections. For streptococcal
pharyngitis, the oral penicillin of choice is penicillin V. In many
clinical trials, a dose of 40 mg/kg/day has been
used. In general, 250 mg two or three times daily is recommended
for most children. In young children, amoxicillin has been used
because of its better taste. The most common reason for penicillin
failure is noncompliance. When oral treatment is prescribed, the
necessity of completing a full course of therapy must be emphasized.
Therapy with benzathine penicillin G is another option. In children
weighing more than 27 kg, 1,200,000 units has been the recommended
dose, and in children weighing less than 27 kg, 600,000 units. Injections
with preparations that contain procaine penicillin are less painful.
The total dose of penicillin is calculated based on the amount of
benzathine penicillin G, as procaine penicillin is rapidly excreted.
++
Even in compliant patients, recent reports have suggested that
penicillin fails to eradicate S pyogenes from up
to 30% of treated patients. Many theories have been proposed
to explain these apparent penicillin failures. The presence of β-lactamase
producing normal flora (particularly mouth anaerobes) has been proposed
as a potential mechanism by which penicillin could become inactivated,
rendering it ineffective. However, the efficacy of this theory has
never been conclusively demonstrated. It is more likely that many
of the “failures” of penicillin therapy occur
in patients in whom streptococcal pharyngitis has not been defined
rigorously enough. Some of these patients are streptococcal carriers
with intercurrent viral pharyngitis.
++
For penicillin-allergic patients, several alternative treatment
options are available. Oral cephalosporins are effective in the
treatment of streptococcal pharyngitis and generally are safe to
use in the penicillin-allergic patient. First-generation cephalosporins
are adequate and are often the least expensive option. Erythromycin estolate
and erythromycin ethylsuccinate are both effective, although caution
must be taken to note local antibiotic resistant rates, as greater than
5% of isolates of S pyogenes may be erythromycin
resistant in some regions of the United States and up to 30% in
some European countries. New macrolides and azalides such as clarithromycin
and azithromycin have similar susceptibility profiles to that of
erythromycin. A 5-day “short” course of azithromycin
has been approved by the Food and Drug Administration for streptococcal
pharyngitis (pediatric dose of 12 mg/kg once a day for
5 days), although recent studies suggest that bacteriologic failure
rates may be unacceptably high at this dose.
++
Treatment of the child with recurrent culture-positive pharyngitis
can be a difficult clinical management problem. It may be difficult
to differentiate a streptococcal carrier from the child with recurrent
bona fide streptococcal pharyngitis. Although most streptococcal
carriers do not require intervention, there are situations in which eradication
of the carrier state is desirable. These include families in which
there is inordinate anxiety about streptococci, families in which “ping pong” spread
has been occurring, or when tonsillectomy is being considered only
because of chronic carriage. A course of clindamycin (20 mg/kg/day
in three divided doses for 10 days) has been shown to be effective
in eradicating the carrier state.20
++
Antibiotic therapy for a patient with streptococcal impetigo
can prevent local extension of the lesions, spread to distant infectious
foci, and transmission of the infection, although the ability of
antibiotics to prevent post-streptococcal glomerulonephritis has
not been clearly demonstrated. Patients with superficial, isolated
lesions and no systemic signs can be treated with topical mupirocin.
However, if there are widespread lesions or systemic signs, oral
therapy with a β-lactamase stable agent should
be used, since mixed infections with S pyogenes and S aureus are
common.
++
Patients with invasive group A streptococcal infections (necrotizing
fasciitis, TSS, sepsis) should be treated with either intravenous penicillin
in combination with clindamycin or with clindamycin alone. The use
of an inhibitor of protein synthesis (such as clindamycin) is useful.
Furthermore, in vivo evidence of the lack of efficacy of penicillin
in deep tissue infections has been observed in animal models. This
effect, first described by Eagle in 1952, appears to be the result
of reduced expression of penicillin-binding proteins, the molecular
targets of penicillin, in the setting of the high inoculum of organisms
encountered in overwhelming infections.21 Supportive
care, including fluids, pressors, and often times mechanical ventilation, is
also a critical aspect of management of invasive streptococcal skin
and soft tissue infections.22 Prompt and repeated
surgical drainage, debridement, or fasciotomy is often indicated.
++
Long-term antibiotic prophylaxis to prevent streptococcal infections
is recommended for patients with a history of acute rheumatic fever
or rheumatic heart disease. The recommended regimen is 3 to 4 weekly
injections of 1.2 million IU of intramuscular benzathine penicillin
G, 250 mg of oral penicillin V twice a day, or 0.5 to 1 g of sulfadiazine
daily. Although no controlled studies have been carried out, 250
mg of erythromycin twice daily has been used in some patients in
this category.
++
The role of prophylaxis for household contacts of patients with
either acute streptococcal infection or nonsuppurative complications
is also controversial. Some authorities recommend that all contacts
should be cultured if there is a family history of rheumatic fever,
or when a patient with acute glomerulonephritis is identified. An
alternative approach is to treat all household contacts in the setting
of acute post-streptococcal glomenulonephritis (PSGN), in an effort
to reduce household transmission of nephritogenic strains. For invasive
group A streptococcal infections (necrotizing fasciitis, TSS), there
are no convincing data on which to predict risk to household contacts.23,24 However,
given the devastating nature of these infections, empiric antibiotic
therapy of household contacts should sometimes be considered.
++
The role of antibiotic prophylaxis for household contacts of
patients with acute streptococcal pharyngitis is generally limited
to contacts of patients who have had rheumatic fever. Many believe
that members of the family should have throat cultures, and those
family members who prove to be positive should be treated. In instances
in which PSGN is present in the family, it has been shown that many
members of the family may have subclinical infection and therefore should
be cultured and treated, as indicated. Apart from rheumatic fever
prophylaxis and the prevention of intrafamilial spread, there are
few strategies available to prevent streptococcal infection. Vaccines
containing multiple M-protein peptide epitopes have been engineered,
and show efficacy in animal models and in some preliminary studies
with human subjects.25,26,27 Until a vaccine is
available, clinicians must remain attentive to the diverse range
of diseases caused by this important pediatric pathogen.