Does Keflex Cover Pseudomonas?
No, Keflex (cephalexin) does not cover Pseudomonas aeruginosa and should never be used when this pathogen is suspected or confirmed. This is a critical clinical distinction that can impact patient outcomes, particularly in serious infections where P. aeruginosa is a concern.
Microbiologic Evidence
Cephalexin has no activity against Pseudomonas species. The FDA-approved drug label explicitly states that cephalexin "has no activity against Pseudomonas spp." 1. This is an intrinsic resistance pattern, not acquired resistance—meaning P. aeruginosa is naturally resistant to this first-generation cephalosporin.
Clinical studies confirm this complete lack of activity:
- In a study of 317 clinical isolates, all Pseudomonas aeruginosa strains were resistant to cephalexin 2
- An ICU surveillance study showed 95.3% resistance of P. aeruginosa to cephalexin 3
- Even among patients treated with cephalexin for urinary tract infections, a significant number became fecal carriers of P. aeruginosa, with one patient developing a urinary tract infection with this organism 4
Clinical Implications by Infection Type
When Pseudomonas Coverage is Required
For infections where P. aeruginosa is a concern, you must use antipseudomonal agents, not cephalexin:
Severe community-acquired pneumonia with risk factors for Pseudomonas:
- Use antipseudomonal cephalosporins (ceftazidime, cefepime) or acylureidopenicillin/β-lactamase inhibitor combinations
- Always combine with either ciprofloxacin OR a macrolide plus aminoglycoside to ensure adequate coverage 5
Febrile neutropenia:
- Monotherapy options include cefepime, carbapenems (imipenem-cilastatin or meropenem), or piperacillin-tazobactam
- P. aeruginosa coverage is essential due to high mortality rates (18%) associated with gram-negative bacteremia in this population 5
Diabetic foot infections with Pseudomonas:
- Use piperacillin-tazobactam for empiric coverage
- Note that P. aeruginosa is uncommon in diabetic foot infections except in special circumstances 5
When Cephalexin is Appropriate
Cephalexin is effective against:
- Staphylococcus aureus (methicillin-susceptible strains only)
- Streptococcus pneumoniae (penicillin-susceptible strains)
- Streptococcus pyogenes
- Select gram-negative organisms: E. coli, H. influenzae, K. pneumoniae, M. catarrhalis, P. mirabilis 1
Appropriate uses include:
- Mild diabetic foot infections (MSSA and Streptococcus coverage) 5
- Prosthetic joint infection suppression for oxacillin-susceptible staphylococci (500 mg PO three to four times daily) 5
- Endocarditis prophylaxis in penicillin-allergic patients without anaphylaxis history 5
Critical Pitfall to Avoid
The most dangerous error is using cephalexin empirically in cystic fibrosis patients. Studies show that chronic cephalexin use in CF patients actually increases the rate of P. aeruginosa acquisition 5. In one trial of 209 young CF children, those treated with cephalexin had higher rates of P. aeruginosa colonization despite lower S. aureus emergence 5. This is why guidelines recommend against prophylactic oral antistaphylococcal antibiotics in CF patients 5.
Spectrum Comparison
To understand where cephalexin fits in the cephalosporin hierarchy:
- First-generation (cephalexin, cefazolin): Good gram-positive coverage, limited gram-negative, no Pseudomonas
- Third-generation (ceftazidime, cefoperazone): Enhanced gram-negative coverage, some have Pseudomonas activity 6
- Fourth-generation (cefepime): Broad spectrum including Pseudomonas coverage 5
Bottom line: If you need Pseudomonas coverage, cephalexin is never the answer. Choose an antipseudomonal β-lactam (cefepime, ceftazidime, piperacillin-tazobactam, or a carbapenem) or a fluoroquinolone like ciprofloxacin 5.