Group A Streptococcal (GAS) Infections Treatment & Management

Physicians must be aware and concerned about the potential for life-threatening complications presented by infection with group A streptococci (GAS). Even seemingly minor infections (eg, pharyngitis, impetigo) may lead to fatal TSS.

Necessary procedures for the management of the diverse nature of GAS infections may include the following:

• Endotracheal intubation

• Thoracocentesis

• Lumbar puncture

• Abscess or skin aspiration

• Prompt surgical drainage

• Surgical débridement of devitalized tissue, fasciotomy, or amputation

In cases of shock, a central venous catheter or a wide-bore peripheral line may be needed immediately for fluid resuscitation.

Some children with recurrent streptococcal pharyngitis (7 culture-proven episodes in the preceding year) may benefit from tonsillectomy.

Children with GAS infection who appear unusually ill require aggressive inpatient evaluation and treatment. Streptococcal infections superimposed on varicella infection (chicken pox) represent a particularly high-risk situation. Aggressive treatment of such infections and close follow-up care are essential.

D ebridement in necrotizing fasciitis

As the lesion in necrotizing fasciitis progresses (approximately 48-72 h), the skin becomes bluish and dusky, and bullae containing yellow or hemorrhagic fluid appear. By the fourth to fifth day, frank gangrene is present, and extensive sloughing of skin occurs. Surgical débridement of necrotic tissue is a crucial adjunct to management. Consultation with a surgeon early in the course of infection is essential because débridement is often lifesaving.

Rehabilitation

Further inpatient care may be necessary in patients with group A streptococcal infections for rehabilitative reasons (eg, in cases of chorea or neuropsychiatric manifestations of infection) or for debilitating arthritis. Consultation with a physical medicine and rehabilitation (PMR) physician, neurologist, or rheumatologist may be useful in these situations.

Pharyngitis

Therapy for streptococcal pharyngitis is aimed primarily at preventing nonsuppurative and suppurative complications and decreasing infectivity. A 10-day course of penicillin V 250 mg twice daily in children and 500 mg twice daily or 250 mg 4 times daily in adults is very effective. A single intramuscular injection of 1.2 million units of penicillin G benzathine can be administered in patients who weigh more than 27 kg; 600,000 units is used in patients who weigh less than 27 kg. Amoxicillin is equally effective and may be better tolerated in children.

Timing of treatment

Sometimes families express concern regarding the delay of 24-48 hours that is required to obtain throat culture findings. Therefore, clinicians feel pressure to immediately initiate therapy, prior to obtaining the result of the culture. However, because starting treatment of GAS sore throat as long as 9 days after the onset of symptoms still effectively prevents rheumatic fever, initiation of antibiotics is seldom of urgent importance. However empiric treatment may be considered based on clinical judgement based on severity of the case and high suspicion for Gr A Strep. 

Early antibiotic therapy may have beneficial effects in relieving symptoms and allowing an earlier return to school or daycare, but early treatment may have disadvantages as well. Several controlled studies have shown 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.

Antibiotic considerations

In patients who are allergic to penicillin, erythromycin or the newer macrolides (eg, azithromycin, clarithromycin) appear to be effective. Oral cephalosporins are also highly effective in the treatment of streptococcal pharyngitis. Although eradication rates associated with cephalosporins may be superior to those achieved with penicillin, the latter is the recommended drug of choice by the American Heart Association and the Infectious Diseases Society of America. ^[2]

A meta-analysis comparing bacterial and clinical cure rates in patients with GAS tonsillopharyngitis found that short-course cephalosporin treatment was superior to 10 days of penicillin for bacterial cure rate, that short-course penicillin therapy was inferior to 10 days of penicillin, and that clinical cure rates were similar to bacterial cure rates. ^[30]

Treatment failure

Treatment failures are uncommon but may occur. If symptoms recur, the throat should be recultured and another course of treatment should be prescribed, preferably with an oral cephalosporin. An asymptomatic carrier state, as evidenced by positive throat culture results obtained on a weekly basis, is not treated with antibiotics.

The most common reason for oral antibiotic failure for streptococcal pharyngitis is noncompliance. Use of the drug is often discontinued before the 10-day course is completed, because individuals usually appear to have recovered in 3-4 days. When oral treatment is prescribed, the necessity of completing a full course of therapy must be emphasized.

Even in compliant patients, reports suggest that penicillin fails to eradicate S pyogenes in 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 in which streptococcal pharyngitis has not been defined rigorously enough, and some of the studies' patients may, in fact, be streptococcal carriers who had viral pharyngitis at the onset of these trials.

Strains of GAS resistant to macrolides have been highly prevalent in some areas of the world and have resulted in treatment failures. The IDSA 2012 guidelines state macrolide resistance rates among pharyngeal isolates in most areas of the United States have been around 5-8%. ^[2]

Impetigo

Streptococcal pyoderma is treated with oral antibiotics (eg, penicillin or erythromycin) for 10 days. However, because concomitant Staphylococcus aureus infection may occur, therapy with cephalexin or cefaclor is suggested. Treatment of pyoderma may not prevent nephritis if the patient is infected with a nephritogenic strain.

Toxic shock syndrome

IV polyspecific immunoglobulin G (IVIG) has been reported to be efficacious as an adjunctive therapy in patients with GAS TSS.

Necrotizing fasciitis

Treatment of necrotizing fasciitis consists of antibiotic therapy, supportive therapy for associated shock, and prompt surgical intervention.

Early and extensive surgical intervention is currently advocated for necrotizing fasciitis. However, a medical regimen, which includes IVIG, may allow an initial nonoperative or minimally invasive management approach, thus limiting the need for extensive débridement and amputation. ^[31]

GAS remain susceptible to beta-lactam antibiotics. Clinical failures of penicillin therapy for streptococcal infections may occur. The failure rates in patients with invasive infections are higher because of the larger number of organisms.

Clindamycin may be more effective in invasive infections. Unlike with penicillin, the efficacy of clindamycin is unaffected by the size of the inoculum and the stage of bacterial growth. In addition, clindamycin inhibits the production of toxin by streptococci.

When treating severe cellulitis Staph aureus should be kept in consideration as a possible alternative pathogen or co-pathogen. Emipric treatment with Vancomycin or Ceftriaxone may be considered and antibiotics should be streamlined based on culture. Clindamycin should be used for toxin inhibition in case of sepsis or septic shock. Patient's allergies should be kept in consideration. 

Linezolid also provides broad spectrum gram positive coverage and has toxin inhibition property. 

Routine throat culture is unnecessary in asymptomatic patients who have completed a course of antibiotic therapy, except in special circumstances. Symptoms that persist after a treatment course may have several explanations, including the following:

• Persistent carriage in the face of intercurrent viral infection

• Noncompliance with the prescribed antimicrobial regimen

• A new GAS infection acquired from family, the classroom, or community contacts

• A recurrent episode of pharyngitis caused by the original infecting strain of GAS (ie, treatment failure)

Streptococcus carriers are unlikely to spread the organism to their close contacts and are at very low risk, if any, of developing suppurative complications or nonsuppurative complications (eg, ARF). Continuous antimicrobial prophylaxis is not recommended except to prevent the recurrence of rheumatic fever in patients who have experienced a previous episode of this disease.

Follow-up culturing of throat swabs is not routinely indicated in asymptomatic patients who have received a complete course of therapy for GAS pharyngitis (A-II), except in those with a history of rheumatic fever. Follow-up throat culturing should also be considered in patients who develop acute pharyngitis during outbreaks of ARF or acute PSGN, during outbreaks of GAS pharyngitis in closed or partially closed communities, or when a "ping-pong" spread of GAS infection has been occurring within a family (B-III). ^[2]

Long-term antibiotic therapy to prevent streptococcal infection is indicated for patients with a history of acute rheumatic fever or rheumatic heart disease. The recommended regimen is 1.2 million international units of benzathine penicillin G injected every 3-4 weeks, 250 mg of oral penicillin V twice daily, or 0.5-1 g of sulfadiazine daily.

Household contacts

The role of prophylaxis for household contacts of individuals with either acute streptococcal disease or nonsuppurative complications is uncertain. The currently available evidence does not justify routine chemoprophylaxis in close contacts. Some authorities recommend that cultures be obtained from all contacts if a family history of rheumatic fever is noted or when a patient with acute glomerulonephritis is identified.

All household contacts of a patient with invasive GAS disease should be informed of the clinical manifestations of invasive disease and counseled to seek immediate medical attention upon development of such symptoms.

An alternative approach to prophylaxis is to treat all household contacts in the setting of acute PSGN in an effort to eradicate household transmission of nephritogenic strains. For invasive GAS infections (eg, necrotizing fasciitis, TSS), no data are available on which to base assessment of risk to household contacts. However, because of the devastating nature of these infections and the observation that invasive disease may be due to clonal outbreaks of more virulent strains, empiric antibiotic therapy of household contacts seems warranted.

Prospects for streptococcal vaccines

Apart from rheumatic fever prophylaxis and the prevention of intrafamily spread, few strategies are available to prevent streptococcal infection. ^[32]

A streptococcal vaccine could be a promising tool for disease prevention, but an effective vaccine would have to provide protection from multiple serotypes. Furthermore, theoretical concern that vaccine-induced antibodies could injure host tissue and precipitate rheumatic fever is recognized.

Multivalent vaccines that contain multiple M-protein peptide epitopes have been engineered and show efficacy in animal models but have not yet entered clinical trials. ^[33] However, several vaccine candidates against GAS infection are in varying stages of preclinical and clinical development, and the hope is that one of these vaccines will reach licensure within the next decade. ^[34] Only the multivalent N-terminal vaccine has entered clinical trials over the last 30 years.

Consultations relating to GAS infections can include the following:

• Surgeon - For necrotizing fasciitis and bone and joint infections

• Critical care specialist - For epiglottitis and TSS

• Nephrologist - For PSGN

• Neurologist - For chorea and PANDAS syndrome

• Infectious diseases specialist - For assistance in differential diagnosis and broad management issues

• Cardiologist - For carditis

• Dermatologist - For skin conditions

• Pathologist - For analysis of biopsies and other intraoperative specimens

• Ear, nose, and throat (ENT) specialist - For complicated pharyngeal infections with peripharyngeal extension, abscess, or Ludwig angina