Group A Streptococcal Infection Medication

Treatment approaches for group A streptococcal infections vary depending on the clinical syndrome. Penicillin therapy, in general, remains the treatment of choice in most situations. Remarkably, no penicillin-resistant strains of S pyogenes have yet been encountered in clinical practice.^[10] Therefore, penicillin remains the drug of choice for pharyngeal infections as well as for complicated or invasive infections, except in individuals who are allergic to penicillin. In those patients who are allergic to penicillin, once-daily therapy with amoxicillin and azithromycin (50 mg/kg) is recommended.^[11] Approaches to antibiotic therapy of various streptococcal syndromes are considered below.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Penicillin VK ( Pfizerpen, Pen-Vee K, Beepen-VK)

Inhibits the biosynthesis of cell wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations are reached, and most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. For streptococcal pharyngitis, the PO antibiotic of choice is penicillin VK (phenoxymethyl penicillin). Penicillin VK is preferable to penicillin G because of its acid stability, allowing it to be dosed without regard to meals. The most common reason for penicillin failure is noncompliance. The drug is often discontinued before the 10-d course is completed because children usually appear to have recovered in 3-4 d. When PO treatment is prescribed, the necessity of completing a full course of therapy must be emphasized. Even in compliant patients, recent reports suggest penicillin fails to eradicate S pyogenes from about 15% of treated patients. Many theories have been proposed to explain these apparent penicillin failures.

The presence of beta-lactamase–producing normal flora (particularly organisms such as mouth anaerobes) is proposed as a potential mechanism by which penicillin may become inactivated. However, the clinical significance of this theory has never been conclusively demonstrated. Many of the failures of penicillin therapy are more likely to occur in studies where streptococcal pharyngitis has not been defined rigorously enough, and some of these patients may, in fact, be streptococcal carriers who had viral pharyngitis at study onset.

Penicillin G benzathine (Bicillin LA)

Interferes with synthesis of cell wall mucopeptides during active multiplication, which results in bactericidal activity. If noncompliance with PO therapy seems likely, parenteral therapy is indicated.

Formulation is painful when administered IM, and it is often combined with penicillin G procaine to minimize discomfort at the injection site. When this combination is used in a single injection, take care to ensure that an adequate amount of penicillin G benzathine is administered. The combination of 900,000 U of penicillin G benzathine and 300,000 U of penicillin G procaine is satisfactory for most children.

Erythromycin (EES, Ery-Tab, E-Mycin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.

In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose. PO erythromycin is an acceptable alternative for patients allergic to penicillin or cephalosporin antibiotics and is effective in the treatment of streptococcal pharyngitis. Erythromycin estolate and erythromycin ethylsuccinate are both effective, although note local antibiotic resistant rates because up to 5% of isolates of S pyogenes may be erythromycin resistant.

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Similar susceptibility profile to erythromycin but has fewer adverse effects.

Azithromycin (Zithromax)

Similar susceptibility profile to erythromycin, but has fewer adverse effects. Treats mild-to-moderate microbial infections.

Cephalexin (Keflex, Biocef)

First-generation cephalosporin arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin flora; used for skin infections or prophylaxis in minor procedures. PO cephalosporins are effective in the treatment of streptococcal pharyngitis.

Short-course regimens of PO cephalosporin therapy have been studied and offer obvious advantages from a compliance perspective. However, this must be balanced against the higher cost and unnecessarily broad spectrum of these agents.

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Patients with invasive group A streptococcal infections (eg, necrotizing fasciitis, TSS, sepsis) should be treated with IV penicillin in combination with clindamycin. Because the pathophysiology of invasive group A streptococcal infection is largely toxin mediated, the use of protein synthesis inhibitor (eg, clindamycin) offers a theoretical advantage.

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 occur because of high inoculum of organisms encountered in overwhelming infections (eg, necrotizing fasciitis, myositis, sepsis).

Large concentrations of organisms lead to rapid attainment of the stationary growth phase, which is associated with decreased expression of cell wall penicillin-binding proteins (PBPs), the molecular targets of penicillin. Decreased expression of PBPs in deep tissue infections with group A streptococci appears to render penicillin less effective. In contrast, clindamycin retains efficacy. Vigorous supportive care, including fluids, pressors, and mechanical ventilation, is also a critical aspect of management of invasive streptococcal skin and soft tissue infections. Prompt surgical drainage, debridement, fasciotomy, or amputation may be indicated.

Differentiating a streptococcal carrier with recurrent viral infection from a child with recurrent streptococcal pharyngitis may be difficult. Although most streptococcal carriers do not require medical intervention, situations arise in which eradication of the carrier state is desirable (eg, families in with an inordinate amount of anxiety about streptococci, families in which ping-pong spread has been occurring, when tonsillectomy is considered only because of chronic carriage). A course of clindamycin has been shown to be highly effective in eradicating the carrier state and should be tried in patients with recurrent or frequent episodes of culture-proven pharyngitis. Some children with recurrent streptococcal pharyngitis (7 culture-proven episodes in the preceding y) may benefit from tonsillectomy.