If Enterococcus Faecalis (E. Faecalis) is resistant to enrofloxacin and marbofloxacin but sensitive to pradofloxacin, would it be expected to be sensitive or resistant to levofloxacin and moxifloxacin?

Fluoroquinolone Cross-Resistance in Enterococcus Faecalis

Enterococcus faecalis that is resistant to enrofloxacin and marbofloxacin but sensitive to pradofloxacin would likely be resistant to levofloxacin and moxifloxacin due to the class effect of fluoroquinolone resistance mechanisms.

Understanding Fluoroquinolone Resistance in Enterococci

• Fluoroquinolone resistance is generally considered a class effect, meaning resistance to one fluoroquinolone often indicates resistance to others in the same class 1
• Enterococcus faecalis has shown increasing resistance to multiple fluoroquinolones in clinical settings 2
• Cross-resistance between fluoroquinolones is common in gram-positive bacteria, including enterococci 3

Specific Resistance Patterns

• Studies have shown that E. faecalis strains with high-level resistance to ciprofloxacin (MIC of 32 mg/L) typically demonstrate cross-resistance to other fluoroquinolones 3
• When E. faecalis develops resistance to one fluoroquinolone, it commonly shows reduced susceptibility to other fluoroquinolones due to shared resistance mechanisms 4
• The resistance is typically mediated by mutations in the bacterial DNA gyrase (gyrA) gene, which affects binding of all fluoroquinolones to varying degrees 3

Comparative Susceptibility Data

• Moxifloxacin is FDA-approved for use against E. faecalis infections, indicating potential activity against susceptible strains 5
• Levofloxacin is indicated for chronic bacterial prostatitis due to E. faecalis, but only for susceptible strains 6
• In studies of fluoroquinolone-resistant E. faecalis, MICs for moxifloxacin were 8-16 mg/L, while MICs for other fluoroquinolones like ofloxacin were ≥128 mg/L, showing some variation in the degree of cross-resistance 3

Clinical Implications

• For prostatic infections with E. faecalis, fluoroquinolones are commonly used, but resistance rates are increasing 2
• In a study of male patients with complicated UTI, 47% of E. faecalis strains were resistant to ciprofloxacin and 46% were resistant to levofloxacin, indicating high levels of cross-resistance 2
• When treating enterococcal infections with documented fluoroquinolone resistance, alternative antimicrobial classes should be considered 1

Unusual Susceptibility Pattern

• The pattern described (resistant to enrofloxacin and marbofloxacin but sensitive to pradofloxacin) is unusual as pradofloxacin is a newer fluoroquinolone that generally follows similar resistance patterns
• This could potentially be explained by:
  • Different binding affinities of pradofloxacin to altered bacterial targets 3
  • Specific mutation patterns that affect some fluoroquinolones more than others 3
  • Variations in efflux pump activity that may preferentially remove certain fluoroquinolones 1

Alternative Treatment Options

• For fluoroquinolone-resistant E. faecalis, especially in prostatic infections, consider:
  • Ampicillin/sulbactam (if susceptible) 2
  • Linezolid for vancomycin-resistant enterococci 1
  • Tigecycline for polymicrobial infections involving resistant enterococci 1
  • Nitrofurantoin for urinary tract infections (if susceptible) 7

Recommendation for Susceptibility Testing

• Given the unusual pattern of fluoroquinolone susceptibility, direct testing of levofloxacin and moxifloxacin susceptibility is strongly recommended rather than assuming cross-resistance 1
• Enterococci should be routinely tested for susceptibility to various antimicrobials due to their propensity for developing resistance 1