Alternative Antibiotics for Penicillin-Allergic Patients with Strep Throat
For patients with confirmed streptococcal pharyngitis who are allergic to penicillin, first-generation cephalosporins (cephalexin or cefadroxil) for 10 days are the preferred alternative, unless the patient has a history of anaphylactic reactions to penicillin. 1
Primary Alternatives Based on Allergy Type
For Non-Anaphylactic Penicillin Allergy
- First-generation cephalosporins (cephalexin or cefadroxil) for 10 days are strongly recommended as the first alternative 1
- These narrow-spectrum agents are preferred over broad-spectrum cephalosporins (cefaclor, cefuroxime, cefixime, cefdinir, cefpodoxime) because they are less expensive and less likely to select for antibiotic-resistant flora 1
- Important caveat: Up to 10% of penicillin-allergic patients are also allergic to cephalosporins, so cephalosporins should be avoided in patients with immediate (anaphylactic-type) hypersensitivity to penicillin 1
For Anaphylactic Penicillin Allergy
When cephalosporins cannot be used, choose between:
- Clindamycin for 10 days - This is a reasonable alternative with only ~1% resistance among GAS isolates in the United States 1
- Clarithromycin for 10 days - Acceptable macrolide option 1
- Azithromycin for 5 days (12 mg/kg/day in children, maximum 500 mg) - Shorter course option, though one study suggests 10 days of clarithromycin may be more effective than 5 days of azithromycin 1
Critical Considerations About Macrolides
Be aware of significant macrolide resistance: Resistance rates to erythromycin, clarithromycin, and azithromycin have been around 5-8% in most areas of the United States in recent years, with higher rates reported in some regions 1, 2
- Erythromycin is associated with substantially higher rates of gastrointestinal side effects and should generally be avoided 1
- Macrolides can cause QT interval prolongation in a dose-dependent manner and should not be taken with cytochrome P-450 3A inhibitors (azole antifungals, HIV protease inhibitors, some SSRIs) 1
Antibiotics to Avoid
Do not use the following for streptococcal pharyngitis:
- Tetracyclines - high prevalence of resistant strains 1
- Sulfonamides and trimethoprim-sulfamethoxazole - do not eradicate GAS 1
- Older fluoroquinolones (ciprofloxacin) - limited activity against GAS 1
- Newer fluoroquinolones (levofloxacin, moxifloxacin) - unnecessarily broad spectrum and expensive 1
Treatment Duration and Follow-up
- All alternatives except azithromycin require 10 days of therapy to effectively eradicate GAS and prevent rheumatic fever 1
- Patients become non-contagious after 24 hours of appropriate antibiotic therapy 1
- Patients with worsening symptoms after appropriate antibiotic initiation or symptoms lasting 5 days after starting treatment should be reevaluated 2