What is the recommended cephalexin dosing regimen for an otherwise healthy adult with confirmed or presumed Group A streptococcal pharyngitis and normal renal function?

Cephalexin Dosing for Streptococcal Pharyngitis in Adults

For an otherwise healthy adult with confirmed Group A streptococcal pharyngitis and normal renal function, prescribe cephalexin 500 mg orally every 12 hours for 10 days. 1

FDA-Approved Dosing Regimen

• The FDA-approved dosing for streptococcal pharyngitis in adults is 500 mg every 12 hours for 10 days. 1
• This twice-daily regimen is as effective as four-times-daily dosing and offers superior adherence while maintaining equivalent bacteriologic cure rates. 2
• The total daily dose should remain within 1 to 4 grams per day. 1

Why Cephalexin Is an Appropriate Choice

• Cephalexin is recommended by IDSA guidelines as a first-line alternative for penicillin-allergic patients with non-immediate (non-anaphylactic) reactions, with strong, high-quality evidence (A-II rating). 3
• First-generation cephalosporins like cephalexin have demonstrated bacteriologic cure rates of 96-97% for Group A streptococcal pharyngitis, comparable to or slightly better than penicillin. 4, 5
• Cephalexin offers narrow-spectrum activity, proven efficacy, low cost, and minimal resistance—making it an excellent choice when penicillin cannot be used. 6

Critical Treatment Duration Requirement

• The full 10-day course is mandatory to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 3, 6
• Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk. 6
• Even if symptoms resolve within 3-4 days, the complete 10-day regimen must be continued. 3

Important Allergy Considerations

• Cephalexin should NOT be used in patients with immediate/anaphylactic penicillin reactions (anaphylaxis, angioedema, respiratory distress, or urticaria within 1 hour) due to up to 10% cross-reactivity risk. 6, 7
• For patients with non-immediate penicillin allergy (delayed rash), the cross-reactivity risk with first-generation cephalosporins is only 0.1%, making cephalexin safe and preferred. 7
• For immediate/anaphylactic penicillin allergy, use clindamycin 300 mg three times daily for 10 days instead. 6

Common Pitfalls to Avoid

• Do not prescribe cephalexin as first-line therapy when penicillin or amoxicillin can be used—penicillin remains the drug of choice for non-allergic patients due to proven efficacy, narrow spectrum, safety, and low cost. 3, 6
• Do not use cephalexin in patients who have had anaphylaxis, angioedema, or immediate urticaria to penicillin—the 10% cross-reactivity risk makes all beta-lactams unsafe in this group. 6, 7
• Do not prescribe broad-spectrum cephalosporins (cefuroxime, cefdinir, cefpodoxime) when cephalexin is appropriate—they are more expensive and more likely to select for antibiotic-resistant flora. 7
• Do not shorten the treatment course below 10 days despite clinical improvement—this dramatically increases treatment failure and rheumatic fever risk. 3, 6

Evidence Supporting Twice-Daily Dosing

• A multicenter, double-blind study of 157 patients demonstrated that cephalexin twice-daily (mean 30 mg/kg/day) and four-times-daily (mean 29 mg/kg/day) regimens had equivalent failure rates of 7.3% and 5.3%, respectively. 2
• The twice-daily regimen can be recommended for improved adherence without compromising efficacy. 2