Is Keflex (Cephalexin) effective against a urinary tract infection (UTI) caused by Enterococcus faecalis?

Keflex (Cephalexin) Is Not Effective for UTIs Caused by Enterococcus faecalis

Keflex (cephalexin) should not be used to treat UTIs caused by Enterococcus faecalis as enterococci are intrinsically resistant to cephalosporins. Instead, several other antibiotics are recommended based on current guidelines.

First-Line Treatment Options for E. faecalis UTIs

• Fosfomycin 3g oral powder as a single dose is recommended for uncomplicated lower UTIs due to E. faecalis 1
• Nitrofurantoin 100mg PO four times daily is effective against E. faecalis with high susceptibility rates (88% in clinical studies) 1, 2
• Ampicillin/Amoxicillin is considered the drug of choice for enterococcal infections if susceptibility is confirmed 1, 3
• Amoxicillin-clavulanic acid is recommended as a first-choice option for lower UTIs according to WHO's Essential Medicines list 3

Why Cephalexin Is Ineffective Against E. faecalis

Enterococci, including E. faecalis, have intrinsic resistance to cephalosporins due to low-affinity penicillin-binding proteins. Despite cephalexin achieving high concentrations in urine 4, it lacks activity against enterococci, making it an inappropriate choice for E. faecalis UTIs.

Treatment Algorithm for E. faecalis UTIs

For Uncomplicated Lower UTIs:

1. First choice: Fosfomycin 3g single dose OR Nitrofurantoin 100mg QID for 5-7 days 1, 3
2. Alternative: Amoxicillin/Amoxicillin-clavulanic acid (if susceptible) 3, 1
3. Duration: 3-7 days is generally sufficient 1

For Complicated or Upper UTIs:

1. First choice: Ampicillin IV (if susceptible) 3
2. Alternatives:
   • For susceptible strains: Piperacillin-tazobactam or vancomycin 3
   • For resistant strains: Linezolid 600mg IV/PO every 12h 1, 3
3. Duration: 7-14 days depending on severity 1

Recent Susceptibility Data

• Recent studies show high susceptibility rates of E. faecalis to nitrofurantoin (88%), ampicillin (72%), and vancomycin (99%) 2
• Fluoroquinolone resistance is increasing, with 47% of E. faecalis strains resistant to ciprofloxacin in one study 5
• A 2025 study confirmed high activity of fosfomycin against E. faecalis isolates from UTIs 6

Risk Factors for Resistant E. faecalis UTIs

• Hospital-acquired infections (18x higher risk of ciprofloxacin resistance) 5
• Patients transferred from healthcare centers (7.4x higher risk) 5
• Previous treatment in urological departments (6.2x higher risk) 5
• Prior use of cephalosporins (selects for Enterococcus species) 3

Important Clinical Considerations

• Differentiate between colonization and true infection before initiating therapy 1
• Consider removing indwelling catheters if present 1, 7
• Avoid unnecessary prolonged use of broad-spectrum antibiotics 1
• Obtain follow-up urine cultures if symptoms persist despite appropriate therapy 1

Common Pitfalls to Avoid

• Using cephalosporins (including Keflex) for E. faecalis UTIs due to intrinsic resistance 3, 1
• Treating asymptomatic bacteriuria, which can foster antimicrobial resistance 1
• Using fluoroquinolones empirically due to high resistance rates (47-58%) 5
• Prolonged therapy which increases risk of resistance and adverse effects 1

In conclusion, when treating UTIs caused by E. faecalis, clinicians should select antibiotics with proven activity against enterococci, such as fosfomycin, nitrofurantoin, or ampicillin, based on susceptibility testing results.