Cephalexin Spectrum of Activity and Dosing
Antimicrobial Spectrum
Cephalexin is a first-generation cephalosporin with activity primarily against Gram-positive cocci (including methicillin-susceptible Staphylococcus aureus and Streptococcus species) and limited Gram-negative coverage, but it has poor activity against Haemophilus influenzae, Moraxella catarrhalis, and is completely ineffective against MRSA. 1, 2
Gram-Positive Coverage
- Excellent activity against methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus species, including beta-hemolytic streptococci 3, 4, 5
- No activity against methicillin-resistant Staphylococcus aureus (MRSA) - alternative agents must be used if MRSA is suspected 3, 4
- Viridans group streptococci show 96% resistance to cephalexin, making it unsuitable for endocarditis prophylaxis 1
Gram-Negative Coverage
- Poor coverage for Haemophilus influenzae - this is a critical limitation that makes cephalexin inappropriate for sinusitis and many respiratory infections 1, 6
- Inadequate activity against beta-lactamase-producing Moraxella catarrhalis 1
- Some activity against common Gram-negative urinary pathogens (E. coli, Proteus) 2, 5
- No activity against Pseudomonas aeruginosa 1
Specific Contraindications
- Completely ineffective for Lyme disease - should never be used 7
- Inappropriate for acute bacterial sinusitis due to poor H. influenzae coverage 1
- Not suitable for infective endocarditis prophylaxis due to high resistance rates 1
Standard Dosing Regimens
Adults
- Standard dose: 500 mg orally every 6 hours (four times daily) for most infections 4, 8
- Alternative for mild infections: 250-500 mg every 6 hours 4, 8
- For streptococcal pharyngitis and uncomplicated skin infections: 500 mg every 12 hours (twice daily) is acceptable 8
- For uncomplicated cystitis: 500 mg every 12 hours for 7-14 days 8
- Maximum daily dose: 4 grams; if higher doses needed, switch to parenteral cephalosporins 8
Pediatric Patients
- Standard dose: 25-50 mg/kg/day divided into 4 doses for mild to moderate infections 4, 8
- For MSSA infections: 75-100 mg/kg/day divided into 3-4 doses 4
- For otitis media: 75-100 mg/kg/day in 4 divided doses (due to H. influenzae concerns, this is often suboptimal) 8
- For streptococcal pharyngitis: May divide total daily dose every 12 hours in children over 1 year 8
- For beta-hemolytic streptococcal infections: Continue for at least 10 days 8
Duration of Therapy
- Typical duration: 7-10 days for most skin and soft tissue infections 3, 4
- Uncomplicated cystitis: 7-14 days 8
- Streptococcal infections: Minimum 10 days 8
Clinical Considerations and Pitfalls
When Cephalexin is Appropriate
- Uncomplicated skin and soft tissue infections caused by MSSA or streptococci 3, 4
- Uncomplicated urinary tract infections in adults 8, 2
- Streptococcal pharyngitis (though penicillin remains first-line) 8
- Mastitis in lactating women (achieves therapeutic levels in breast milk) 4
Critical Pitfalls to Avoid
- Do not use for sinusitis: First-generation cephalosporins like cephalexin have poor H. influenzae coverage and are inappropriate for this indication 1
- Do not use if MRSA suspected: Switch immediately to trimethoprim-sulfamethoxazole, clindamycin, or other MRSA-active agents 3, 4
- Do not use for Lyme disease: Completely ineffective 7
- Do not use for endocarditis prophylaxis: High resistance rates make it unreliable 1
- Avoid in pediatric respiratory infections: Poor H. influenzae coverage limits utility, especially in otitis media and pneumonia 1, 6
Pharmacokinetic Advantages
- Rapidly and completely absorbed from the upper intestine (not stomach) 2
- Achieves urinary concentrations of 500-1000 mcg/mL after 250-500 mg doses 2
- Does not disturb lower bowel flora due to high intestinal absorption 2
- Low protein binding and no metabolism - excreted unchanged in urine 2
- Renal dose adjustment required: Reduce dose proportionally when creatinine clearance <30 mL/min 2