Cephalexin for Upper Respiratory Tract Infections
Cephalexin is NOT recommended as a first-line antibiotic for most upper respiratory tract infections (URTIs), and first-generation cephalosporins like cephalexin are specifically excluded from guideline recommendations for respiratory infections due to inadequate activity against key pathogens, particularly Streptococcus pneumoniae with decreased penicillin susceptibility. 1
Why Cephalexin Is Not Recommended for URTIs
Guideline Exclusions
- First-generation oral cephalosporins are explicitly NOT recommended for respiratory tract infections in children or adults due to inadequate activity against penicillin-resistant S. pneumoniae 1
- The European Society of Clinical Microbiology and Infectious Diseases specifically states that first-generation cephalosporins should not be used because of their inadequate activity against S. pneumoniae with decreased susceptibility to penicillin 1
Limited Spectrum Issues
- While the FDA label indicates cephalexin can be used for "respiratory tract infections caused by Streptococcus pneumoniae and Streptococcus pyogenes," this indication predates current resistance patterns and guideline recommendations 2
- Cephalexin has a 50% failure rate in infections caused by Haemophilus influenzae, a common URTI pathogen, particularly in otitis media 3
- This limitation significantly reduces its effectiveness in pediatric populations and in acute exacerbations of chronic bronchitis 4
What Should Be Used Instead
For Bacterial Sinusitis (When Antibiotics Are Indicated)
- Amoxicillin-clavulanate is the first-line treatment for maxillary sinusitis when antibiotics are necessary 5
- Second-generation cephalosporins (cefuroxime-axetil) or specific third-generation cephalosporins (cefpodoxime-proxetil, cefotiam-hexetil) are acceptable alternatives 5, 6
- Note: Cefixime, despite being third-generation, is specifically NOT recommended due to inactivity against pneumococci with decreased penicillin susceptibility 6
For Streptococcal Pharyngitis
- Penicillin remains the drug of choice for Group A Streptococcus pharyngitis 2
- While cephalexin is "generally effective in the eradication of streptococci from the nasopharynx," penicillin is preferred 2
- Cefadroxil (another first-generation cephalosporin) can be used as a first-line option specifically for pharyngitis/tonsillitis caused by Streptococcus pyogenes, but this is the exception rather than the rule 6
For Most URTIs
- Most URTIs are viral and require only supportive care - antibiotics cause more harm than benefit 5
- Supportive care includes analgesics, antipyretics, saline nasal irrigation, intranasal corticosteroids, and decongestants as needed 5
The One Narrow Exception
Streptococcal Pharyngitis/Tonsillitis Only
- Cephalexin may be considered for documented Group A Streptococcal pharyngitis in patients with penicillin allergy (non-anaphylactic type) 2, 3
- However, even in this scenario, it is not the preferred first-line agent 2
Critical Clinical Pitfalls to Avoid
- Do not use cephalexin for otitis media - the 50% failure rate with H. influenzae makes it unreliable 3
- Do not use cephalexin for sinusitis - it lacks adequate coverage for the most common pathogens and resistant strains 1, 6
- Do not use cephalexin empirically for URTIs without documented streptococcal infection - most URTIs are viral 5
- Do not assume all cephalosporins are equivalent - second and third-generation agents have significantly better activity against respiratory pathogens than first-generation drugs like cephalexin 1, 5
Bottom Line Algorithm
For any URTI presentation:
- First, determine if antibiotics are even indicated (most are viral) 5
- If bacterial infection is confirmed or strongly suspected, identify the specific diagnosis
- For sinusitis → use amoxicillin-clavulanate or cefuroxime-axetil, NOT cephalexin 5, 6
- For streptococcal pharyngitis → use penicillin; cephalexin only if penicillin-allergic 2
- For otitis media → avoid cephalexin due to H. influenzae resistance 3