Keflex Dosage for Adult GAS Pharyngitis
For adults with Group A Streptococcal pharyngitis, cephalexin (Keflex) should be dosed at 500 mg orally every 12 hours for 10 days. 1, 2
When to Use Cephalexin for GAS Pharyngitis
Cephalexin is not first-line therapy for strep throat. It should be reserved specifically for patients with non-immediate (non-anaphylactic) penicillin allergy. 1, 3
- Penicillin V (250 mg four times daily or 500 mg twice daily) or amoxicillin (500 mg twice daily) remains the drug of choice for all non-allergic patients due to proven efficacy, narrow spectrum, safety, and low cost. 1, 4
- First-generation cephalosporins like cephalexin have strong, high-quality evidence supporting their use as the preferred alternative for penicillin-allergic patients without immediate hypersensitivity. 1, 3
Critical Allergy Assessment Required
You must determine the type of penicillin allergy before prescribing cephalexin:
- Safe to use cephalexin: Non-immediate reactions (delayed rash, mild gastrointestinal symptoms occurring >1 hour after administration). Cross-reactivity risk is only 0.1%. 3
- Avoid cephalexin: Immediate/anaphylactic reactions (anaphylaxis, angioedema, respiratory distress, urticaria within 1 hour of penicillin). Up to 10% cross-reactivity risk with all beta-lactams including cephalosporins. 1, 3
Alternative Options for Immediate Penicillin Allergy
If the patient has immediate/anaphylactic penicillin allergy, avoid all cephalosporins and use: 1, 3
- Clindamycin 300 mg orally three times daily for 10 days (preferred choice, ~1% resistance rate in US) 1, 3, 4
- Azithromycin 500 mg on day 1, then 250 mg daily for days 2-5 (acceptable alternative, but 5-8% macrolide resistance in US) 1, 3, 4
- Clarithromycin 250 mg twice daily for 10 days (acceptable alternative, similar resistance concerns as azithromycin) 1, 3, 4
Why the Full 10-Day Course is Non-Negotiable
The complete 10-day course of cephalexin is essential to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever, even if symptoms resolve within 3-4 days. 1, 3, 5
- Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk. 3, 5
- Azithromycin is the only exception requiring just 5 days due to its prolonged tissue half-life. 1, 3, 5
- Therapy can be safely postponed up to 9 days after symptom onset and still prevent rheumatic fever. 3, 5
Evidence Supporting Cephalexin Efficacy
The FDA label specifically states that for streptococcal pharyngitis, 500 mg may be administered every 12 hours in adults. 2
- Clinical studies demonstrate that cephalexin twice-daily and four-times-daily regimens are equally effective for GAS pharyngitis, with failure rates of 7.3% and 5.3% respectively. 6
- Cephalexin achieves cure rates of 96.7%, comparable to oral penicillin (97.1%) and intramuscular benzathine penicillin (96.4%). 7
Common Pitfalls to Avoid
- Do not use cephalexin in patients with immediate hypersensitivity to penicillin due to the 10% cross-reactivity risk. 1, 3
- Do not prescribe shorter courses than 10 days (except azithromycin's 5-day regimen) as this increases treatment failure and rheumatic fever risk. 1, 3, 5
- Do not prescribe broad-spectrum cephalosporins (cefdinir, cefixime, cefpodoxime) when narrow-spectrum cephalexin is appropriate—they are more expensive and more likely to select for antibiotic-resistant flora. 3
- Do not assume all penicillin-allergic patients need macrolides—most can safely receive first-generation cephalosporins if the allergy is non-immediate. 3
Additional Clinical Considerations
- Patients are no longer contagious after 24 hours of appropriate antibiotic therapy but must complete the full 10-day course. 4, 5
- Routine follow-up throat cultures are not recommended for asymptomatic patients who have completed therapy. 3, 5
- Acetaminophen or NSAIDs can be used for moderate to severe symptoms or high fever as adjunctive therapy. 3, 5
- Corticosteroids are not recommended as adjunctive therapy. 3, 5