Keflex (Cephalexin) Is NOT Effective Against Sinusitis
Cephalexin should not be used to treat acute bacterial sinusitis due to inadequate coverage against Haemophilus influenzae, one of the three most common causative pathogens. 1, 2
Why Cephalexin Fails in Sinusitis
Pathogen Coverage Gap
The three primary bacterial pathogens in acute sinusitis are Streptococcus pneumoniae (33-41%), Haemophilus influenzae (29-35%), and Moraxella catarrhalis (4-8%). 1, 3 First-generation cephalosporins like cephalexin have poor coverage for H. influenzae and are therefore deemed inappropriate for sinusitis treatment. 2
- Nearly 50% of H. influenzae strains produce β-lactamase, rendering them resistant to first-generation cephalosporins 2
- 90-100% of M. catarrhalis strains are β-lactamase producing 2
- While the FDA label indicates cephalexin has in vitro activity against H. influenzae, this does not translate to clinical efficacy in sinusitis where β-lactamase-producing strains predominate 4
Guideline Recommendations Explicitly Exclude Cephalexin
The American Academy of Allergy and Clinical Immunology recommends against using cephalexin for treating acute bacterial sinusitis due to inadequate coverage against H. influenzae. 2 This represents a clear contraindication based on microbiologic principles and clinical outcomes.
What Should Be Used Instead
First-Line Treatment Options
Amoxicillin-clavulanate 875 mg/125 mg twice daily for 5-10 days is the preferred first-line antibiotic for acute bacterial sinusitis in adults. 1, 2 The clavulanate component provides essential coverage against β-lactamase-producing organisms. 1
Alternative first-line options include:
- Plain amoxicillin 500 mg twice daily (mild disease) or 875 mg twice daily (moderate disease) for patients without recent antibiotic exposure 1, 2
- High-dose amoxicillin-clavulanate (2 g/125 mg twice daily) for patients with recent antibiotic use, age >65 years, or moderate-to-severe symptoms 1
For Penicillin-Allergic Patients: Use Second or Third-Generation Cephalosporins
Second-generation cephalosporins (cefuroxime, cefprozil) or third-generation cephalosporins (cefpodoxime, cefdinir) are appropriate alternatives for penicillin-allergic patients—NOT first-generation agents like cephalexin. 1, 2
- Cefuroxime axetil has enhanced activity against β-lactamase-producing H. influenzae and M. catarrhalis 3
- Cefpodoxime and cefdinir provide adequate coverage against both H. influenzae and S. pneumoniae 1, 3
- These agents should be dosed for 10 days 1
Second-Line Options for Treatment Failure
If no improvement occurs after 3-5 days of first-line therapy, switch to:
- Respiratory fluoroquinolones (levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily) for 10 days 1, 2
- These provide 90-92% predicted clinical efficacy against drug-resistant S. pneumoniae and β-lactamase-producing organisms 1
Historical Context: Why This Matters
A 1985 study showed cephalexin achieved 83% clinical success in maxillary sinusitis 5, but this predates the widespread emergence of β-lactamase-producing H. influenzae and M. catarrhalis. Current resistance patterns make cephalexin obsolete for sinusitis treatment. 2, 6 The microbiology of sinusitis has fundamentally changed, with β-lactamase production now the dominant resistance mechanism. 6
Critical Pitfall to Avoid
Do not use first-generation cephalosporins (cephalexin, cefadroxil) for sinusitis due to inadequate coverage against H. influenzae. 2 This represents a common prescribing error that leads to treatment failure and promotes antimicrobial resistance.