What is the recommended treatment for urinary tract infections caused by Enterococcus (E.) faecalis with a minimum inhibitory concentration (MIC) of <=16.0 for nitrofurantoin?

Nitrofurantoin for E. faecalis UTI with MIC ≤16 mg/L

Nitrofurantoin 100 mg PO every 6 hours is an effective treatment option for uncomplicated urinary tract infections caused by E. faecalis with an MIC ≤16 mg/L, as this organism demonstrates excellent in vitro susceptibility to nitrofurantoin and the drug achieves high urinary concentrations. 1

Treatment Recommendation

For uncomplicated lower urinary tract infections caused by E. faecalis, nitrofurantoin 100 mg orally every 6 hours is recommended. 1 This recommendation is supported by:

• High susceptibility rates: 88-100% of E. faecalis isolates remain susceptible to nitrofurantoin, including vancomycin-resistant strains 2, 3, 4, 5
• Retained efficacy: Nitrofurantoin maintains antimicrobial activity even against multidrug-resistant E. faecalis, with 80.76% of vancomycin-resistant E. faecalis remaining susceptible 2
• FDA approval: Nitrofurantoin was approved by the U.S. FDA in the 1950s specifically for treatment of lower urinary tract infections and has good in vitro activity against enterococci 1

MIC Interpretation

An MIC of ≤16 mg/L for nitrofurantoin against E. faecalis indicates susceptibility, as:

• Research demonstrates that E. faecalis MIC₉₀ values for nitrofurantoin are consistently ≤16 mg/L 6
• No E. faecalis isolates tested in multiple studies showed resistance (defined as MIC ≥128 μg/mL) to nitrofurantoin 3

Alternative First-Line Options

If nitrofurantoin is contraindicated or for more severe infections:

• Ampicillin remains the drug of choice for E. faecalis infections when the organism is susceptible (penicillin MIC ≤8 mg/L) 1, 7
• High-dose ampicillin (18-30g IV daily in divided doses) or amoxicillin (500 mg PO/IV every 8 hours) can be used for uncomplicated UTIs, as high urinary concentrations may overcome resistance 1, 7
• Fosfomycin 3g PO single dose is FDA-approved for UTI caused by E. faecalis and recommended for uncomplicated VRE UTIs 1

Important Clinical Considerations

Limitations of Nitrofurantoin

• Restricted to lower UTI only: Nitrofurantoin should NOT be used for pyelonephritis, complicated UTIs, or systemic enterococcal infections due to inadequate tissue penetration 1
• Renal function requirement: Avoid in patients with creatinine clearance <30-50 mL/min due to reduced urinary drug concentrations
• Duration: Typically 5-7 days for uncomplicated cystitis in women

E. faecalis vs E. faecium

E. faecalis is significantly more susceptible to antibiotics than E. faecium, with only 3% of E. faecalis strains being multidrug-resistant compared to up to 95% of E. faecium 7. This distinction is critical:

• E. faecalis: 96-100% susceptible to ampicillin and nitrofurantoin 4, 5
• E. faecium: Only 32-50% susceptible to ampicillin and nitrofurantoin 4

Differentiate Colonization from Infection

Always confirm true infection rather than colonization before initiating antimicrobial therapy, as enterococci are normal gastrointestinal flora and frequently colonize the urinary tract without causing disease 1, 7

For Complicated or Systemic E. faecalis Infections

If the infection extends beyond uncomplicated lower UTI (e.g., endocarditis, bacteremia, pyelonephritis):

• Ampicillin 2g IV every 4 hours combined with gentamicin (if aminoglycoside-susceptible) for 4-6 weeks for endocarditis 1, 7
• Double beta-lactam therapy (ampicillin plus ceftriaxone) offers comparable efficacy with less nephrotoxicity for gentamicin-resistant strains 1, 7
• Vancomycin 30 mg/kg per 24h IV in 2 divided doses for penicillin-allergic patients 7
• Daptomycin 8-12 mg/kg/day for vancomycin-resistant E. faecalis bacteremia 1, 7