Antibiotic Selection for Streptococcal Infection with Penicillin Allergy
For patients with non-immediate (non-anaphylactic) penicillin allergy, use a first-generation cephalosporin such as cephalexin 500 mg twice daily for 10 days in adults or 20 mg/kg/dose twice daily for 10 days in children. 1, 2
For patients with immediate/anaphylactic penicillin allergy (history of anaphylaxis, angioedema, respiratory distress, or urticaria), use clindamycin 300 mg three times daily for 10 days in adults or 7 mg/kg/dose three times daily (maximum 300 mg/dose) for 10 days in children. 1, 2
Treatment Algorithm Based on Allergy Type
Step 1: Determine the Type of Penicillin Allergy
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. 3, 1, 2
Non-immediate reactions (delayed rash, mild gastrointestinal symptoms) carry only 0.1% cross-reactivity risk with first-generation cephalosporins, making them safe and preferred. 1, 2
Step 2: Select Appropriate Antibiotic
For Non-Immediate Penicillin Allergy (Preferred Options):
Cephalexin: 500 mg orally twice daily for 10 days (adults) or 20 mg/kg/dose twice daily for 10 days (children, maximum 500 mg/dose)—this has strong, high-quality evidence supporting efficacy and is the preferred first-line alternative. 1, 2
Cefadroxil: 1 gram orally once daily for 10 days (adults) or 30 mg/kg once daily for 10 days (children, maximum 1 gram)—equally effective with once-daily convenience. 1, 2
For Immediate/Anaphylactic Penicillin Allergy (Must Avoid All Beta-Lactams):
Clindamycin (PREFERRED): 300 mg orally three times daily for 10 days (adults) or 7 mg/kg/dose three times daily for 10 days (children, maximum 300 mg/dose)—this has only ~1% resistance among Group A Streptococcus in the United States and demonstrates superior eradication rates even in chronic carriers. 1, 2
Azithromycin: 500 mg orally once daily for 5 days (adults) or 12 mg/kg once daily for 5 days (children, maximum 500 mg)—this is FDA-approved for streptococcal pharyngitis and requires only 5 days due to prolonged tissue half-life, but has 5-8% macrolide resistance in the United States. 1, 2, 4
Clarithromycin: 250 mg orally twice daily for 10 days (adults) or 7.5 mg/kg/dose twice daily for 10 days (children, maximum 250 mg/dose)—similar efficacy to azithromycin but requires full 10-day course. 1, 2
Critical Treatment Duration Requirements
All antibiotics except azithromycin require a full 10-day course to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever—shortening the course by even a few days results in appreciable increases in treatment failure rates. 1, 2
Azithromycin is the only exception, requiring only 5 days due to its unique pharmacokinetics and prolonged tissue half-life. 1, 2, 4
Important Resistance Considerations
Clindamycin resistance remains very low at approximately 1% among Group A Streptococcus isolates in the United States, making it the most reliable non-beta-lactam option. 1, 2
Macrolide resistance (azithromycin, clarithromycin, erythromycin) is approximately 5-8% in the United States but varies geographically—some areas experience much higher rates, making clindamycin preferred when beta-lactams cannot be used. 1, 2
First-generation cephalosporins have essentially 0% resistance and strong, high-quality evidence for efficacy in non-anaphylactic penicillin-allergic patients. 1, 2
Common Pitfalls to Avoid
Do NOT use cephalosporins in patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, respiratory distress, urticaria within 1 hour)—the 10% cross-reactivity risk makes this unsafe. 1, 2
Do NOT assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them; patients with delayed, non-severe reactions have only 0.1% cross-reactivity risk. 1, 2
Do NOT prescribe shorter courses than recommended (except azithromycin's 5-day regimen)—this dramatically increases treatment failure and acute rheumatic fever risk. 1, 2
Do NOT use broad-spectrum cephalosporins (cefdinir, cefixime, cefpodoxime) when narrow-spectrum first-generation agents (cephalexin, cefadroxil) are appropriate—they are more expensive and more likely to select for antibiotic-resistant flora. 1
Do NOT ignore local macrolide resistance patterns—in areas with high macrolide resistance, clindamycin or first-generation cephalosporins are strongly preferred over azithromycin or clarithromycin. 1, 2
Special Considerations for Group B Streptococcus (Pregnant Women)
For pregnant women requiring intrapartum antibiotic prophylaxis with non-immediate penicillin allergy: cefazolin 2 grams IV initial dose, then 1 gram IV every 8 hours until delivery. 3, 2
For pregnant women with immediate/anaphylactic penicillin allergy and susceptible isolate: clindamycin 900 mg IV every 8 hours until delivery (requires susceptibility testing). 3, 2