Does Keflex (Cephalexin) Cover Gram-Negative Rods?
Cephalexin provides limited and unreliable coverage against gram-negative rods and should not be relied upon as primary therapy for infections caused by these organisms.
Spectrum of Activity Against Gram-Negative Organisms
Organisms with Documented Activity
- Cephalexin demonstrates in vitro activity against Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, which are the primary gram-negative rods it can reliably cover 1.
- The FDA label confirms cephalexin is active against these three Enterobacteriaceae species both in vitro and in clinical infections 1.
Organisms with Poor or No Activity
- Cephalexin has no activity against Pseudomonas species or Acinetobacter calcoaceticus, making it completely inappropriate for infections involving these pathogens 1.
- It is not active against most strains of Enterobacter species, Morganella morganii, and Proteus vulgaris 1.
- Cephalexin demonstrates poor activity against Haemophilus influenzae and Moraxella catarrhalis, limiting its utility in respiratory tract infections where these organisms are common 2.
Clinical Implications and Limitations
When Gram-Negative Coverage Is Inadequate
- For acute bacterial sinusitis and many respiratory infections, cephalexin should be avoided due to inadequate H. influenzae coverage 2.
- Cephalexin has inadequate activity against beta-lactamase-producing M. catarrhalis, further restricting its use in upper respiratory infections 2.
Comparative Potency
- Among first-generation cephalosporins tested against gram-negative bacilli (E. coli, K. pneumoniae, P. mirabilis), cefazolin demonstrates superior activity compared to cephalexin 3.
- Historical data show that only 49.1% of tested organisms were suppressed by cephalexin at concentrations of 3.13 mcg/mL or less, compared to higher suppression rates with other cephalosporins 3.
Appropriate Clinical Use
- Cephalexin remains highly effective for gram-positive infections (streptococcal and staphylococcal skin and soft-tissue infections), where it achieves cure rates of 90% or higher 4.
- For mixed infections or when gram-negative coverage is essential, amoxicillin-clavulanate or broader-spectrum agents should be selected instead 5.
Key Pitfalls to Avoid
- Do not use cephalexin for polymicrobial infections involving anaerobes or resistant gram-negative organisms, as it lacks adequate coverage 2.
- Do not prescribe cephalexin for diabetic foot infections or other polymicrobial soft-tissue infections where broader gram-negative and anaerobic coverage is required 5.
- Avoid cephalexin for bite-related cellulitis (human or animal), where Pasteurella multocida, Eikenella corrodens, and anaerobes require amoxicillin-clavulanate or alternative regimens 5, 6.