What are the first‑line treatment options for streptococcal infection in an adult who is allergic to trimethoprim‑sulfamethoxazole (Bactrim) and nitrofurantoin (Macrobid)?

Streptococcal Coverage in Adults Allergic to Bactrim and Macrobid

First-Line Treatment Recommendations

For streptococcal pharyngitis in adults allergic to trimethoprim-sulfamethoxazole and nitrofurantoin, use penicillin V 250 mg orally twice daily or amoxicillin as first-line therapy, as these remain the drugs of choice for streptococcal infections. 1

Key Point on Allergy Context

• Neither Bactrim (trimethoprim-sulfamethoxazole) nor Macrobid (nitrofurantoin) are first-line agents for streptococcal infections, so allergies to these agents do not significantly alter standard streptococcal treatment algorithms 1
• Bactrim has poor activity against beta-hemolytic streptococci and should not be used for streptococcal coverage 2

Treatment Algorithm by Clinical Scenario

For Streptococcal Pharyngitis (Primary Indication)

Preferred agents:

• Penicillin V 250 mg orally twice daily for 10 days 1
• Amoxicillin (standard or high-dose depending on resistance risk) 1

If penicillin allergic (non-Type I hypersensitivity/mild reactions):

• Oral cephalosporins (cefdinir, cefpodoxime, or cefuroxime) 1
• Cefdinir is preferred based on patient acceptance 1

If true penicillin allergy (Type I hypersensitivity):

• Macrolides: azithromycin or clarithromycin 1, 3
• Doxycycline as alternative 1
• Erythromycin (though newer macrolides better tolerated) 1, 3

For Sinusitis with Streptococcal Coverage

If penicillin-allergic with non-Type I hypersensitivity:

• Doxycycline 1
• Respiratory fluoroquinolones (levofloxacin or moxifloxacin) 1

Important caveat: Macrolides and trimethoprim-sulfamethoxazole are NOT recommended for initial therapy of acute bacterial rhinosinusitis due to high resistance rates (>40% for macrolides, 50% for TMP-SMX against S. pneumoniae) 1

For Community-Acquired Pneumonia with Streptococcal Coverage

Outpatient without cardiopulmonary disease:

• Advanced-generation macrolide (azithromycin or clarithromycin) 1
• Doxycycline as alternative 1

Outpatient with cardiopulmonary disease or risk factors:

• Beta-lactam (high-dose amoxicillin, amoxicillin/clavulanate, or ceftriaxone) PLUS macrolide or doxycycline 1
• Antipneumococcal fluoroquinolone as monotherapy alternative 1

Critical Caveats and Pitfalls

Resistance Considerations

• High-dose amoxicillin (90 mg/kg/day or 2g twice daily in adults) is preferred over standard dosing in areas with >10% penicillin-nonsusceptible S. pneumoniae 1
• Geographic regions with high endemic rates of resistant streptococci require consideration of higher doses or alternative agents 1

Duration of Therapy

• Streptococcal pharyngitis requires 10 days of penicillin therapy to prevent acute rheumatic fever 1, 3
• Azithromycin can be given for 5 days due to prolonged tissue half-life 3
• Clarithromycin and erythromycin require 10-day courses 3

Common Prescribing Errors to Avoid

• Do not use TMP-SMX for streptococcal pharyngitis—it lacks adequate streptococcal activity 2
• Do not use nitrofurantoin for systemic streptococcal infections—it is only indicated for urinary tract infections 4
• Avoid fluoroquinolones as first-line for simple pharyngitis due to higher adverse event rates and need to preserve them for resistant infections 1

Special Populations

• For patients on penicillin prophylaxis for rheumatic fever who develop endocarditis, use an agent other than penicillin due to likely resistance 1
• Sulfonamides (including TMP-SMX) are contraindicated in late pregnancy 1