Is cephalexin appropriate for treating acute streptococcal (Group A) pharyngitis, and what are the recommended doses for children and adults, especially in a patient with a non‑anaphylactic penicillin allergy?

Cephalexin for Streptococcal Pharyngitis

Cephalexin Is Appropriate for Non-Anaphylactic Penicillin Allergy

For patients with non-immediate (delayed) penicillin allergy and confirmed Group A streptococcal pharyngitis, cephalexin is a highly appropriate first-line alternative with strong, high-quality evidence supporting its efficacy. 1, 2

Determining Allergy Type Is Critical

• Immediate/anaphylactic reactions (anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin exposure) carry up to 10% cross-reactivity risk with all cephalosporins—these patients must avoid cephalexin entirely. 1, 3

• Non-immediate (delayed) reactions (mild rash or skin symptoms occurring >1 hour after exposure) have only 0.1% cross-reactivity risk with first-generation cephalosporins, making cephalexin safe and preferred. 1, 3

Recommended Dosing Regimens

Adults

• Cephalexin 500 mg orally every 12 hours for a full 10-day course is the standard regimen for streptococcal pharyngitis in adults with non-anaphylactic penicillin allergy. 1, 4

Pediatric Patients

• Cephalexin 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days is recommended for children over 1 year of age. 1, 4

• Alternatively, 25–50 mg/kg/day divided into 2–4 doses may be used, with the twice-daily regimen specifically approved for streptococcal pharyngitis. 4

• For severe infections or β-hemolytic streptococcal infections, 75–100 mg/kg/day in 4 divided doses may be required, though the twice-daily regimen is typically adequate for uncomplicated pharyngitis. 4

Why the Full 10-Day Course Is Mandatory

• All antibiotics except azithromycin require a complete 10-day course to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1, 2, 3

• Shortening the course by even a few days leads to appreciable increases in treatment failure rates and rheumatic fever risk, even if symptoms resolve within 3–4 days. 1, 2

Evidence Supporting Cephalexin Efficacy

• Cephalexin demonstrates superior bacteriologic eradication compared to penicillin in multiple studies, with combined treatment failure rates (clinical relapse plus asymptomatic bacteriologic failure) of 10% for cephalexin versus 19% for penicillin. 5

• Meta-analyses show cephalosporins may have slightly better bacterial eradication rates than penicillin, though clinical differences are small. 1

• First-generation cephalosporins have strong, high-quality evidence for efficacy in non-anaphylactic penicillin-allergic patients, with narrow spectrum activity, proven efficacy, and low cost. 1, 2

When Cephalexin Cannot Be Used

For Immediate/Anaphylactic Penicillin Allergy

• Clindamycin 300 mg orally three times daily for 10 days (adults) or 7 mg/kg per dose three times daily for 10 days (children, maximum 300 mg/dose) is the preferred alternative, with only ~1% resistance among U.S. Group A Streptococcus isolates. 1, 3

• Azithromycin 500 mg once daily for 5 days (adults) or 12 mg/kg once daily for 5 days (children, maximum 500 mg) is acceptable, but macrolide resistance is 5–8% in the United States. 1, 2

• Clarithromycin 250 mg twice daily for 10 days (adults) or 7.5 mg/kg per dose twice daily for 10 days (children, maximum 250 mg/dose) is another macrolide option with similar resistance concerns. 1, 2

Common Pitfalls to Avoid

• Do not prescribe cephalexin to patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, immediate urticaria) to penicillin due to the 10% cross-reactivity risk. 1, 3

• Do not shorten the cephalexin course below 10 days (except azithromycin's 5-day regimen), as this markedly increases treatment failure and rheumatic fever risk. 1, 2

• Do not prescribe broad-spectrum cephalosporins (cefaclor, cefuroxime, cefixime, cefdinir, cefpodoxime) when narrow-spectrum first-generation agents like cephalexin are appropriate—they are more expensive and more likely to select for antibiotic-resistant flora. 1

• Do not order routine post-treatment throat cultures for asymptomatic patients who have completed therapy; reserve testing for special circumstances such as history of rheumatic fever. 1

Adjunctive Symptomatic Treatment

• Acetaminophen or NSAIDs (ibuprofen) should be offered for moderate to severe symptoms or high fever, with strong evidence for pain and inflammation reduction. 1, 2, 3

• Aspirin must be avoided in children due to Reye syndrome risk. 1, 2, 3

• Corticosteroids are not recommended as adjunctive therapy. 1, 2

Why Cephalexin Over Other Alternatives

• Cephalexin is preferred over macrolides (azithromycin, clarithromycin) for non-anaphylactic penicillin allergy due to stronger evidence (strong, high-quality versus strong, moderate-quality), lower resistance rates (essentially 0% versus 5–8%), narrower spectrum, and lower cost. 1, 2

• Cephalexin is more cost-effective than broader-spectrum cephalosporins while maintaining excellent efficacy against Group A Streptococcus. 1, 6