Keflex (Cephalexin) is NOT a Good Option for Sinusitis Unresponsive to Augmentin
Keflex should not be used for sinusitis that has failed Augmentin therapy, as it provides inferior coverage against the key pathogens causing treatment failure—specifically β-lactamase-producing Haemophilus influenzae, Moraxella catarrhalis, and drug-resistant Streptococcus pneumoniae. 1, 2
Why Keflex Fails in This Scenario
Keflex (cephalexin) is a first-generation cephalosporin that lacks adequate activity against the organisms most likely responsible for Augmentin failure. 3 While the FDA label indicates cephalexin covers S. pneumoniae and H. influenzae for respiratory infections, this reflects susceptible strains only—not the resistant organisms encountered after Augmentin failure. 3
The Coverage Gap Problem
When Augmentin (amoxicillin-clavulanate) fails after 3-5 days, the likely culprits are:
- Drug-resistant S. pneumoniae (DRSP) 4, 1
- β-lactamase-producing H. influenzae and M. catarrhalis that have developed resistance beyond what clavulanate can overcome 1
Keflex provides inadequate coverage against these resistant pathogens, making treatment failure highly likely. 1, 2
What You Should Use Instead
First-Line Recommendation: Respiratory Fluoroquinolones
For Augmentin failure, switch to a respiratory fluoroquinolone—either levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily for 10-14 days. 1, 2 These agents provide:
- 90-92% predicted clinical efficacy 1
- Excellent coverage against drug-resistant S. pneumoniae (including multi-drug resistant strains) 1
- Complete coverage of β-lactamase-producing H. influenzae and M. catarrhalis 1, 2
Alternative Options: Second or Third-Generation Cephalosporins
If fluoroquinolones are contraindicated, use second-generation cephalosporins (cefuroxime-axetil) or third-generation cephalosporins (cefpodoxime, cefdinir) for 10-14 days. 4, 1 These provide superior activity compared to first-generation agents like Keflex:
- Cefpodoxime or cefdinir offer superior activity against H. influenzae compared to cefuroxime 1
- Cefuroxime-axetil provides adequate coverage but has limited activity against drug-resistant S. pneumoniae 1
High-Dose Augmentin as an Option
Consider escalating to high-dose amoxicillin-clavulanate (4 g amoxicillin/250 mg clavulanate per day) for 10-14 days, which provides enhanced coverage against drug-resistant S. pneumoniae. 4, 1 However, this may not address β-lactamase-producing organisms that have already demonstrated resistance. 1
Treatment Algorithm After Augmentin Failure
Reassess at 3-5 days: If no improvement on Augmentin, switch antibiotics immediately 4, 1
First choice: Respiratory fluoroquinolone (levofloxacin 500 mg or moxifloxacin 400 mg once daily for 10-14 days) 1, 2
Alternative if fluoroquinolones contraindicated: Third-generation cephalosporin (cefpodoxime or cefdinir) for 10-14 days 4, 1
Add adjunctive therapy: Intranasal corticosteroids to reduce mucosal inflammation 4, 1
Consider short-term oral corticosteroids if marked mucosal edema is present 4, 1
Reassess at 7 days: If still no improvement, refer to ENT for evaluation of complications, anatomic abnormalities, or alternative diagnoses 4, 1
Critical Pitfalls to Avoid
Never use first-generation cephalosporins (like Keflex) for treatment failures, as they lack adequate coverage against resistant organisms 1, 2
Avoid macrolides (azithromycin) due to resistance rates exceeding 20-25% for both S. pneumoniae and H. influenzae 1
Do not continue ineffective therapy beyond 3-5 days—early recognition of treatment failure and prompt switching is essential 4, 1
Reserve fluoroquinolones appropriately: While they are the best option for Augmentin failure, avoid using them as first-line therapy to prevent resistance development 1, 2
Historical Context: Why Keflex Was Once Used
An older 1985 study showed cephalexin effectiveness in maxillary sinusitis 5, but this predates the current era of widespread antibiotic resistance. Modern guidelines explicitly recommend second or third-generation cephalosporins—not first-generation agents like Keflex—for treatment failures. 4, 1