Keflex Coverage Against Gram-Positive Bacilli
Keflex (cephalexin) has limited activity against Gram-positive bacilli, with reliable coverage only for Proteus mirabilis among this group, while lacking activity against most other Gram-positive bacilli including Bacillus species, Listeria, and Corynebacterium. 1
FDA-Approved Spectrum for Gram-Positive Bacilli
The FDA label for cephalexin specifically lists only one Gram-positive bacillus in its approved indications:
- Proteus mirabilis: Approved for bone infections and genitourinary tract infections 1
Notably absent from the FDA label are other clinically relevant Gram-positive bacilli, indicating lack of reliable activity against these organisms 1.
Clinical Microbiology Data
Research confirms cephalexin's limited Gram-positive bacilli coverage:
- Proteus mirabilis: 56% of strains inhibited by 12.5 mcg/mL, with 90% inhibited by 25 mcg/mL 2
- Other Gram-positive bacilli: The FDA label explicitly notes cephalexin "has no activity against Pseudomonas spp." and is "not active against most strains of Enterobacter spp., Morganella morganii, and Proteus vulgaris" 1
Important Gram-Positive Bacilli NOT Covered
Cephalexin lacks activity against clinically important Gram-positive bacilli including:
- Bacillus species: Guidelines note these organisms "are susceptible only to vancomycin" 3
- Corynebacterium jeikeium: Requires vancomycin therapy 3
- Listeria monocytogenes: Not mentioned in cephalexin's spectrum and requires ampicillin-based therapy
- Anaerobic Gram-positive bacilli: Cephalosporins generally have poor anaerobic coverage 3
Comparison to Other Cephalosporins
When comparing first-generation cephalosporins for Gram-positive coverage:
- Cephalexin was "less active against viridans group streptococci than other first-generation oral cephalosporins" 3
- Against Staphylococcus aureus, only 49.1% of strains were suppressed by cephalexin at 3.13 mcg/mL, compared to >90% for cefazolin, cephaloridine, and cephalothin 4
- The relative potency against S. aureus in decreasing order is: cephaloridine > cephalothin > cefazolin > cephalexin 4
Clinical Pitfalls to Avoid
Do not use cephalexin for:
- Suspected Bacillus species infections (including B. anthracis) - requires vancomycin or fluoroquinolones 3
- Corynebacterium infections - requires vancomycin 3
- Listeria infections - requires ampicillin-based therapy
- Infections requiring coverage of anaerobic Gram-positive bacilli - requires metronidazole or other anaerobic agents 3, 5
Appropriate Clinical Use
Cephalexin is appropriate for Gram-positive bacilli only when:
- Proteus mirabilis is confirmed as the pathogen in bone or urinary tract infections 1
- Susceptibility testing confirms the isolate is sensitive to cephalexin 1
- The infection is not severe enough to warrant broader-spectrum therapy 6
The drug achieves adequate serum levels (mean peak 7.7 mcg/mL with 250 mg dose, 12.3 mcg/mL with 500 mg dose) and excellent urinary concentrations (>1000 mcg/mL) to treat susceptible P. mirabilis 1, 2.