What is the best outpatient antibiotic for streptococcal (strep) infection in a patient allergic to amoxicillin and Bactrim (trimethoprim/sulfamethoxazole)?

Best Outpatient Antibiotic for Strep in Amoxicillin and Bactrim-Allergic Patients

For a patient allergic to both amoxicillin and Bactrim, clindamycin 300 mg orally three times daily for 10 days is the best choice, offering approximately 99% eradication rates with only 1% resistance among Group A Streptococcus in the United States. 1

Critical Allergy Assessment

The type of amoxicillin allergy determines your options:

• If the amoxicillin allergy is immediate/anaphylactic (hives, angioedema, bronchospasm within 1 hour), you must avoid ALL beta-lactam antibiotics including cephalosporins due to up to 10% cross-reactivity risk 1, 2
• If the amoxicillin allergy is non-immediate (delayed rash, mild reactions), first-generation cephalosporins like cephalexin carry only 0.1% cross-reactivity risk and would be acceptable 1
• Since Bactrim (trimethoprim-sulfamethoxazole) is contraindicated and should never be used for strep throat due to 50% resistance rates and lack of efficacy against Group A Streptococcus 1, this eliminates another common alternative

Recommended Treatment: Clindamycin

Clindamycin is your best option because:

• Dosing: 300 mg orally three times daily for 10 days in adults; 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days in children 1, 3
• Efficacy: Demonstrates 97.9% bacteriologic eradication at day 12 and 99.2% at 3-month follow-up 4
• Resistance: Only approximately 1% resistance among Group A Streptococcus isolates in the United States 1
• Special advantage: Particularly effective in chronic streptococcal carriers who have failed penicillin treatment 1, 2

Alternative Option: Azithromycin (Second-Line)

If clindamycin cannot be used, azithromycin is acceptable but less preferred:

• Dosing: 500 mg orally once daily for 5 days in adults; 12 mg/kg once daily (maximum 500 mg) for 5 days in children 1, 3
• Advantage: Only requires 5 days due to prolonged tissue half-life 1, 5
• Disadvantage: 5-8% macrolide resistance in the United States, varying geographically 1, 5
• Critical limitation: No data proving azithromycin prevents rheumatic fever, unlike penicillin 5

Critical Treatment Duration

• The full 10-day course of clindamycin is mandatory to achieve maximal pharyngeal eradication and prevent acute rheumatic fever 1
• Shortening the course even by a few days dramatically increases treatment failure rates and rheumatic fever risk 1
• Azithromycin is the only exception requiring just 5 days 1, 5

Common Pitfalls to Avoid

• Do not use first-generation cephalosporins (like cephalexin) if the amoxicillin allergy was immediate/anaphylactic—the 10% cross-reactivity risk makes this dangerous 1, 2
• Never use Bactrim for strep throat—it has 50% resistance rates and is not recommended for Group A Streptococcus 1
• Do not prescribe azithromycin as first-line when clindamycin is available—clindamycin has lower resistance rates (1% vs 5-8%) and better evidence 1
• Do not stop antibiotics early even if symptoms resolve in 3-4 days—the goal is preventing rheumatic fever, not just symptom relief 1

Adjunctive Therapy

• Consider acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever 1
• Avoid aspirin in children due to Reye syndrome risk 1
• Do not use corticosteroids 1