Keflex (Cephalexin) is NOT Appropriate for Uncomplicated Upper Respiratory Infections
Antibiotics, including Keflex (cephalexin), should not be prescribed for uncomplicated upper respiratory infections (URIs) because the vast majority are viral in origin and antibiotic treatment provides no benefit while exposing patients to unnecessary harm. 1, 2, 3
Why Antibiotics Are Not Indicated for Most URIs
- Most URIs are viral: Fewer than 2% of viral URIs progress to bacterial complications such as acute bacterial rhinosinusitis 4, 2
- No clinical benefit: Multiple guidelines confirm that antibiotic treatment does not enhance illness resolution in nonspecific URIs 3, 1
- Purulent discharge is misleading: Discolored or purulent nasal discharge alone does NOT indicate bacterial infection—it simply reflects inflammation and is commonly seen in viral infections 1, 2, 3
Specific Problems with Cephalexin for URIs
- Wrong spectrum of activity: While the FDA label indicates cephalexin is approved for respiratory tract infections caused by Streptococcus pneumoniae and Streptococcus pyogenes, these are NOT the typical pathogens in uncomplicated URIs 5
- Poor coverage for common bacterial URI pathogens: When bacterial infection does occur (e.g., acute bacterial rhinosinusitis), the most important pathogen is S. pneumoniae, but resistance patterns make cephalexin a poor choice compared to amoxicillin 4, 1
- Oral cephalosporins have high resistance rates: Guidelines specifically note that oral third-generation cephalosporins have poor efficacy against pneumococcal infections due to resistance, making first-generation agents like cephalexin even less appropriate 4
When to Consider Antibiotics (But Not Cephalexin)
Antibiotics should ONLY be considered when specific clinical criteria suggest bacterial infection:
- Persistent symptoms >10 days without improvement 4, 1, 2
- Severe symptoms: High fever (>39°C), purulent nasal discharge, and facial pain for ≥3 consecutive days 4, 1, 2
- Worsening course: "Double sickening" pattern where symptoms initially improve then worsen 4, 1, 2
Even when bacterial infection is suspected, amoxicillin—NOT cephalexin—is the first-line agent 1, 2. Amoxicillin-clavulanate is reserved for patients with risk factors for resistance (recent antibiotic use within 30 days, concurrent conjunctivitis) 4, 2.
Harms of Inappropriate Antibiotic Use
- Adverse events are common: Number needed to harm is only 8, while number needed to treat for bacterial URIs is 18 2
- Gastrointestinal effects: Diarrhea and rash occur in approximately 5% of patients, with rates up to 44% for amoxicillin-clavulanate 4
- Antibiotic resistance: Inappropriate use drives resistance at both individual and community levels 4
- Serious reactions: Risk of Stevens-Johnson syndrome, anaphylaxis, and C. difficile infection 4
Appropriate Management of Uncomplicated URIs
- Symptomatic treatment only: Acetaminophen or ibuprofen for pain/fever 1, 2
- Supportive care: Adequate hydration, rest, saline nasal irrigation 1, 2
- Decongestants: Oral or topical if no contraindications 1
- Watchful waiting: Most symptoms resolve within 7-10 days without antibiotics 4, 1
Critical Pitfall to Avoid
Do not prescribe antibiotics based on patient expectation, purulent discharge, or duration of symptoms alone. The decision must be based on strict clinical criteria suggesting bacterial infection 4, 1. When bacterial infection IS confirmed and antibiotics are warranted, amoxicillin—not cephalexin—is the evidence-based first-line choice 1, 2.