Amoxicillin plus

A single injection of 1.2

million

Penicillin's efficacy in preventing rheumatic fever is well established, and is related to the eradication of the organism from the pharynx. This efficacy, however, is dependent upon prolonged, rather than high-dose, therapy.

Penicillin has been shown effective when therapy is started within 9 days of onset of symptoms of GAS pharyngitis (90). Other desirable features of penicillin include lower cost, lower side effects, and a narrow antimicrobial spectrum. There has been no documentation of resistance in GAS to penicillin; the minimal bactericidal concentration of penicillin G for GAS has remained 0.005 ?g/mL (reviewed in 76).

Erythromycin remains the first alternate choice in patients who are allergic to penicillin. Erythromycin estolate (20 - 40 mg/ kg/day) or erythromycin ethylsuccinate (40 mg/kg/day) given enterally in 2 to 4 divided doses has been shown as effective as penicillin in treatment of pharyngitis.

However, documented reports of erythromycin-resistant GAS have occurred in Finland, Japan, and, most recently, in the United States (57,58,75,92). In 1970, resistance to erythromycin in Japan had increased to 70% of all isolates, corresponding to a marked increase in macrolide use during that time (30).

Use of macrolides since then has declined, and a marked decrease in rates of erythromycin resistance has followed (30).

Resistance rates fell to 46% in 1981 and are currently at 3% (1989) (30). In Finland, erythromycin resistance reached 25% and was highest among strains isolated from soft tissue infections (75).

The newest macrolides, azithromycin and clarithromycin , have been shown highly effective in the treatment of GAS pharyngitis. They provide easier dosing schedules and thus improve patient compliance. Azithromycin has been shown to be efficacious in the treatment of GAS pharyngitis when given for only 3 - 5 days.

For example, a recent study comparing azithromycin (20 mg/kg, once daily for 3 days) with

penicillin

for

improvement

The ability of macrolides to prevent episodes of rheumatic fever has not been studied. Amoxicillin has been shown to be effective in eradicating GAS, is more palatable, and provides easier dosing than penicillin.

Oral cephalosporins have been extensively studied in the treatment of GAS pharyngitis and are highly effective.

In fact, some studies have suggested greater efficacy with cephalosporins than with penicillin, possibly because of their resistance to ?-lactamase producing organisms in the pharynx (70); other studies have not supported this (76).

Cephalexin can be given at 30 mg/day, in four divided doses for 10 days; cefadroxil , 30 mg/kg/day, in two divided doses forns10 days; cefaclor , 30 mg/kg/day in three divided doses for 10 days; cefuroxime axetil, 15 mg/kg/day in two

divided

In addition, cephalosporins as a class are more expensive than penicillin, are associated with greater side effects in general, and have a broader spectrum of activity.

In many areas, tetracycline resistance occurs in a high percentage of strains of GAS and thus, this drug is not recommended for treatment of pharyngitis. Sulfonamides , including trimethoprim-sulfamethoxazole, are ineffective in the treatment of GAS pharyngitis, though sulfadiazine has proven useful for prophylaxis in acute rheumatic fever (8,47).

Treatment failures in GAS pharyngitis are of major concern in the prevention of rheumatic fever.

Studies have reported failure rates as high as 30%, including studies of penicillin G given one time amoxicillin 1mg intramuscularly (76).

Noncompliance is thought to play a major role with oral treatments but does not account for all failures, however, it is unlikely that bacteriologic failures in the treatment of GAS are due solely to ?-lactamase-flora colonizing a patient's pharynx (76).

Some investigators have postulated that early treatment of GAS, within 48 h of symptoms, impairs the patient=s immune response by altering the course of the illness. In fact, studies have shown that delaying therapy for 3 to 5 days resulted in an increase in anti-streptolysin O antibodies but did not affect development of type-specific antibodies (32). Antibodies such as anti-streptolysin O, unlike

type-specific

Some bacteriologic and clinical failures may also represent infection with a tolerant strain or acquisition of a new strain of GAS.

In addition, GAS carriers with an intercurrent viral pharyngitis may be mistakenly diagnosed as patients with acute GAS

pharyngitis

Clindamycin has been extremely effective in the treatment of GAS.

It is unaffected by the activity of ?-lactamases, but is more expensive than penicillin and has been associated with development of pseudomembranous colitis in some patients.

In patients with recurring episodes of GAS pharyngitis or persistent, culture-positive, clinical GAS pharyngitis, it is often necessary to change antibiotic therapy. Usually, a 10 day course of amoxicillin/clavulanate , clindamycin, or an oral cephalosporin eradicates the GAS. Therapies shown to be effective in eliminating the carrier state include clindamycin (20 mg/kg/day in 3 divided doses over 10 days), amoxicillin/clavulanate given for 10 days, oral rifampin (20 mg/kg every 24 h

for

rifampin

Tonsillectomy may help reduce the number of acute infections in children with GAS pharyngitis (see below section VI AAdjunctive Therapy@).

S carlet Fever: Scarlet fever is characterized by high fever, circumoral pallor and a diffuse erythematous rash over the neck, trunk, face and limbs. There is a sandpaper consistency to the rash which blanches with pressure.

A white coating over the tongue resolves quickly leaving a strawberry appearance to the tongue owing to the swollen papillae.

The treatment of scarlet fever is the same as that for GAS pharyngitis as the disease usually results from infection of the pharynx with a streptococcal strain that elaborates one of the streptococcal pyrogenic exotoxin (8).

Scarlet fever can also result from GAS infections at other sites, such as the skin (8).

Patients in modern times resolve the illness in 5-7 days and by 10-14 days there may be impressive desquamation of the skin particularly over the hands and feet.

S oft-Tissue Infections Due to GAS: The second most common clinical manifestation of GAS is a localized, relatively benign, infection of the skin.

Recent reports have documented increased frequency and severity of invasive group A streptococcal infections of the skin and soft tissues, associated with group A streptococcal serotypes M-1 and M-3 (7).

This is of considerable interest because these serotypes are more often associated with episodes of pharyngitis. Strains of group A streptococci that cause skin infections normally differ from those that cause pharyngitis and can be identified by their M serotypes. The most common streptococcal M serotypes that cause pharyngitis (types 1, 3, 5, 6, 12, 18, 19, 24 and others), including M-1 and M-3, have rarely been identified in skin lesions (8). In contrast, "skin strains" have been found to colonize the pharynx but are rarely associated with acute episodes of pharyngitis (8). G AS Pyoderma (Streptococcal Impetigo, Impetigo Contagiosum, Ecthyma): Pyoderma is a term for a localized purulent infection of the skin and is used synonymously with streptococcal impetigo and impetigo contagiosa. Pyoderma is most common in children aged 2 to 5 years and occurs most commonly among economically disadvantaged children in tropical or subtropical climates but can occur in northern climates during the summer months.

It normally results from direct inoculation of the skin surface with GAS

following

Penicillin was effective treatment in the past but is now often associated with treatment failures. First line therapy includes dicloxacillin , cephalexin , or cefadroxil .

Erythromycin is an alternative for penicillin-allergic patients but must be used with caution in regions where erythromycin-resistant strains of S. Mupirocin ointment (applied to skin lesions 3 times daily for 10 days) has achieved cure rates comparable to those with enteral therapy but is more expensive.

While rheumatic fever is not an associated complication of pyoderma, skin infections caused by nephritogenic strains of group A streptococci are the major antecedent of post-streptococcal glomerulonephritis (reviewed in (7)). E rysipelas: Erysipelas is an acute inflammation of the skin with involvement of cutaneous lymphatic vessels. It is most commonly found in infants and adults over 30 years of age.

Historically, erysipelas most commonly involved the face.

However, recent reports document up to 85% of infections involving the legs and feet (7).

It is often preceded by a sore throat and

commonly