Does Cephalexin Kill Group A Strep?
Yes, cephalexin is effective against Group A Streptococcus (Streptococcus pyogenes) and is FDA-approved for treating infections caused by this organism, though penicillin remains the preferred first-line agent. 1
Microbiological Activity
- Cephalexin demonstrates bactericidal activity against Group A Streptococcus, with the FDA label specifically indicating its use for respiratory tract infections, skin and soft tissue infections, and otitis media caused by S. pyogenes. 1
- Group A streptococci have maintained 100% susceptibility to penicillin worldwide, and first-generation cephalosporins like cephalexin share similar activity against these organisms. 2
- Clinical studies demonstrate bacteriologic cure rates of 81-93% for cephalexin in Group A streptococcal pharyngitis, which compares favorably to penicillin's 70-89% cure rates. 3, 4, 5
Clinical Positioning in Treatment Guidelines
Cephalexin is recommended as a second-line alternative for penicillin-allergic patients, not as first-line therapy:
- The IDSA explicitly states that penicillin remains the drug of choice for Group A streptococcal infections due to proven efficacy, safety, narrow spectrum, and low cost. 6
- For patients with penicillin allergy (excluding immediate hypersensitivity reactions), the IDSA recommends cephalexin at 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days. 7
- The WHO Working Group selected cephalexin as a second-line option based on lower relapse rates, good tolerability, and narrower spectrum compared to macrolides. 7
Critical Contraindications
Cephalexin must be avoided in patients with immediate-type penicillin allergies:
- Patients with a history of anaphylaxis, angioedema, or urticaria to penicillins should NOT receive cephalexin due to up to 10% cross-reactivity risk with beta-lactam antibiotics. 6, 7
- In these high-risk allergic patients, clindamycin or azithromycin should be used instead. 7
- This cross-reactivity warning appears consistently across American Heart Association, IDSA, and American Academy of Family Physicians guidelines. 6, 7
Dosing Regimens
Standard 10-day treatment course:
- Adults: 250-500 mg four times daily OR 500 mg twice daily for 10 days. 7
- Pediatrics: 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days. 7
- The 10-day duration is necessary to maximize bacterial eradication and prevent rheumatic fever, regardless of which antibiotic is used. 2
- Twice-daily dosing has been shown equally effective as four-times-daily dosing, improving compliance without sacrificing efficacy. 8, 5
Comparative Efficacy Evidence
Cephalexin may actually outperform penicillin in some clinical scenarios:
- A large randomized double-blind crossover study of 525 children found combined treatment failure rates of 10% for cephalexin versus 19% for penicillin (p<0.05). 3
- Meta-analysis of five studies showed failure rates of 11% for oral cephalosporins versus 23% for penicillin (p<0.001), with odds of failure 2.4 times greater with penicillin. 4
- Despite these findings, penicillin remains guideline-recommended first-line therapy due to its narrower spectrum, lower cost, and decades of proven effectiveness in preventing rheumatic fever. 6, 2
Important Clinical Caveats
Resistance considerations for viridans streptococci (not Group A):
- While Group A streptococci remain universally susceptible, cephalexin shows 96% resistance among viridans group streptococci, making it the least active cephalosporin tested. 7
- This resistance pattern is relevant for endocarditis prophylaxis but does NOT apply to Group A streptococcal pharyngitis or skin infections. 7
- For endocarditis prophylaxis in penicillin-allergic patients, cefazolin or ceftriaxone are preferred over cephalexin due to superior activity. 6, 7
Cost-effectiveness considerations: