Does Keflex (cephalexin) cover streptococcal infections?

Does Keflex Cover Streptococcal Infections?

Yes, Keflex (cephalexin) provides excellent coverage for streptococcal infections and is recommended as a first-line agent by major infectious disease guidelines for most streptococcal skin and soft tissue infections. 1, 2

FDA-Approved Indications for Streptococcal Coverage

The FDA label explicitly lists cephalexin as indicated for respiratory tract infections caused by Streptococcus pneumoniae and Streptococcus pyogenes (Group A strep), as well as skin and skin structure infections caused by Streptococcus pyogenes. 2 The label notes that while penicillin remains the usual drug of choice for streptococcal infections and rheumatic fever prophylaxis, cephalexin is generally effective in eradicating streptococci from the nasopharynx. 2

Guideline-Supported Clinical Applications

Skin and Soft Tissue Infections

The IDSA strongly recommends cephalexin as a first-line oral agent for typical cellulitis and erysipelas, which are predominantly caused by streptococci. 1 Suitable oral regimens include penicillin, amoxicillin, dicloxacillin, or cephalexin for most patients with uncomplicated cellulitis. 1 Treatment duration of 5 days is as effective as 10 days if clinical improvement occurs. 1

Impetigo and Ecthyma

For impetigo (both bullous and nonbullous) and ecthyma, the IDSA recommends 7-day oral therapy with an agent active against S. aureus unless cultures yield streptococci alone—in which case oral penicillin is the recommended agent. 1 When methicillin-susceptible S. aureus is suspected (the usual scenario), dicloxacillin or cephalexin is recommended. 1

Streptococcal Pharyngitis

For Group A streptococcal pharyngitis in penicillin-allergic patients (without history of anaphylaxis), the IDSA recommends cephalexin 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days. 3 The WHO Working Group selected cephalexin as a second-line option based on lower relapse rates, good tolerability, and narrow spectrum compared to macrolides. 3

Standard Dosing Regimens

• Adults: 250-500 mg four times daily OR 500 mg twice daily for 10 days 3
• Pediatrics: 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 3
• Skin infections: 25-50 mg/kg/day in divided doses 1

Critical Contraindications and Limitations

Penicillin Allergy Cross-Reactivity

Patients with immediate/anaphylactic penicillin reactions (history of anaphylaxis, angioedema, or urticaria) should NOT receive cephalexin due to up to 10% cross-reactivity risk. 3 These patients should receive clindamycin or azithromycin instead. 3 The American Academy of Family Physicians specifically recommends avoiding cephalexin in patients with these severe penicillin allergy histories. 3

Viridans Group Streptococci Resistance

Cephalexin shows 96% resistance among viridans group streptococci blood culture isolates, making it the least active cephalosporin tested. 3 For endocarditis prophylaxis in penicillin-allergic patients, cefazolin or ceftriaxone are 2-4 times more active than cephalexin and should be preferred. 3

When NOT to Use Cephalexin

Do not use cephalexin if MRSA is suspected or confirmed, as indicated by purulent drainage with abscess formation, penetrating trauma, concurrent MRSA infection elsewhere, or known high local MRSA prevalence. 4 For MRSA coverage, switch to vancomycin, linezolid, daptomycin, clindamycin, doxycycline, or trimethoprim-sulfamethoxazole. 4

Clinical Efficacy Data

Clinical studies demonstrate 90% or higher cure rates for streptococcal and staphylococcal skin infections with cephalexin. 5 In pharyngitis and tonsillitis due to beta-hemolytic streptococci, cephalexin is comparable to penicillin as measured by clinical response, bacteriological cure rate, and incidence of relapse. 6 A randomized controlled trial showed no significant difference between penicillins and cephalosporins for cellulitis treatment (RR 0.99; 95% CI 0.68-1.43). 4

Important Clinical Pearls

• Cephalexin has poor activity against Pasteurella multocida and should be avoided for animal bites—use amoxicillin-clavulanate instead. 4
• For dual streptococcal and MRSA coverage when needed, combine cephalexin with either trimethoprim-sulfamethoxazole or doxycycline. 1, 4
• The IDSA notes that MRSA is an uncommon cause of typical cellulitis, and β-lactam monotherapy (including cephalexin) was successful in 96% of patients in high-MRSA prevalence settings. 1
• Cephalexin is cost-effective, with generic formulations widely available and relatively inexpensive compared to newer agents. 3