Treatment of Beta-Hemolytic Streptococcal Infections in Penicillin-Allergic Patients
For patients with non-immediate (delayed, non-anaphylactic) penicillin allergy, prescribe a first-generation cephalosporin such as cephalexin 500 mg orally twice daily for 10 days; for patients with immediate/anaphylactic penicillin reactions, prescribe clindamycin 300 mg orally three times daily for 10 days. 1
Determine the Type of Penicillin Allergy First
The critical first step is distinguishing between immediate and non-immediate reactions, as this determines whether cephalosporins can be safely used. 2, 1
Immediate/anaphylactic reactions include anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin administration—these patients must avoid all beta-lactam antibiotics including cephalosporins due to up to 10% cross-reactivity risk. 2, 1
Non-immediate reactions (delayed rash, mild skin reactions occurring >1 hour after administration) carry only 0.1% cross-reactivity risk with first-generation cephalosporins, making them safe and preferred alternatives. 1
Treatment Algorithm Based on Allergy Type
For Non-Immediate (Non-Anaphylactic) Penicillin Allergy
First-generation cephalosporins are the preferred first-line alternatives with strong, high-quality evidence. 1
Cephalexin 500 mg orally twice daily for 10 days (adult dosing) or 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days in children. 1
Cefadroxil 1 gram orally once daily for 10 days (adult dosing) or 30 mg/kg once daily (maximum 1 gram) for 10 days in children. 1
These agents have a narrow spectrum, proven efficacy, low cost, and essentially 0% resistance among Group A Streptococcus. 1
For Immediate/Anaphylactic Penicillin Allergy
Clindamycin is the preferred choice with strong, moderate-quality evidence. 1
Clindamycin 300 mg orally three times daily for 10 days (adults) or 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days in children. 1
Clindamycin has approximately 1% resistance among Group A Streptococcus in the United States and demonstrates high efficacy even in chronic carriers. 1
Clindamycin is particularly effective for treatment failures and chronic carriers who have failed penicillin treatment. 1
Acceptable macrolide alternatives (though less preferred due to resistance concerns):
Azithromycin 500 mg orally once daily for 5 days (adults) or 12 mg/kg once daily (maximum 500 mg) for 5 days in children—the only antibiotic requiring just 5 days due to prolonged tissue half-life. 1, 3
Clarithromycin 250 mg orally twice daily for 10 days (adults) or 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days in children. 1
Macrolide resistance among Group A Streptococcus is 5-8% in the United States and varies geographically, making clindamycin more reliable. 1
Critical Treatment Duration Requirements
A full 10-day course is mandatory for all antibiotics except azithromycin to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1
Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk. 1
Even if symptoms resolve within 3-4 days, the full 10-day course must be completed. 1
Azithromycin is the only exception, requiring only 5 days due to its unique pharmacokinetics and prolonged tissue half-life. 1, 3
Important Resistance Considerations
Clindamycin resistance remains very low at approximately 1% in the United States, making it the most reliable non-beta-lactam option. 1
Macrolide resistance (azithromycin, clarithromycin) ranges from 5-8% nationally but varies geographically—some areas have much higher rates. 1
No documented penicillin resistance exists in Group A Streptococcus anywhere in the world. 1
Common Pitfalls to Avoid
Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions—the 10% cross-reactivity risk makes all beta-lactams unsafe in this group. 1
Do not assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them; patients with delayed reactions can safely use first-generation cephalosporins. 1
Do not prescribe broad-spectrum cephalosporins (cefaclor, cefuroxime, cefixime, cefdinir, cefpodoxime) when narrow-spectrum first-generation agents are appropriate—they are more expensive and more likely to select for antibiotic-resistant flora. 1
Do not shorten antibiotic courses below 10 days (except azithromycin's 5-day regimen)—this dramatically increases treatment failure and rheumatic fever risk. 1
Do not use trimethoprim-sulfamethoxazole (Bactrim)—it fails to eradicate Group A Streptococcus in 20-25% of cases and is absolutely contraindicated for streptococcal pharyngitis. 1
Special Clinical Situations
Impetigo and Ecthyma (Skin and Soft Tissue Infections)
When streptococci alone are the cause, penicillin is the drug of choice, with a macrolide or clindamycin as an alternative for penicillin-allergic patients. 2
Unless cultures yield streptococci alone, antimicrobial therapy should be active against both S. aureus and streptococci—oral penicillinase-resistant penicillin or first-generation cephalosporins are usually effective. 2
Alternatives for penicillin-allergic patients or infections with MRSA include doxycycline, clindamycin, or SMX-TMP. 2
Intrapartum Antibiotic Prophylaxis for Group B Streptococcus
For pregnant women with non-anaphylactic penicillin allergy requiring intrapartum prophylaxis, cefazolin is recommended. 2
For women with immediate/anaphylactic penicillin allergy, clindamycin or vancomycin should be used depending on susceptibility testing results. 2
Antimicrobial susceptibility testing for clindamycin and erythromycin should be ordered for antenatal GBS cultures in penicillin-allergic women at high risk for anaphylaxis. 2
Severe Invasive Infections (Necrotizing Fasciitis, Toxic Shock Syndrome)
For necrotizing fasciitis and streptococcal toxic shock syndrome, combination therapy with clindamycin plus penicillin is recommended: penicillin 2-4 million units IV every 4-6 hours plus clindamycin 600-900 mg IV every 8 hours. 1
This combination has superior efficacy versus penicillin alone, as clindamycin suppresses production of streptococcal pyrogenic exotoxins and modulates cytokine production. 1