Enterococcus faecalis and Fluoroquinolone Susceptibility
Yes, it is true that E. faecalis has naturally low fluoroquinolone susceptibility and can be suppressed but rarely eradicated by levofloxacin due to its propensity for rapid mutation. This characteristic has important implications for treatment strategies and outcomes.
Natural Resistance Patterns of E. faecalis
- E. faecalis demonstrates intrinsic reduced susceptibility to fluoroquinolones, including levofloxacin, compared to many other bacterial species 1
- Fluoroquinolones display a much slower rate of kill against E. faecalis compared to other gram-positive organisms like staphylococci, requiring cell division for bactericidal activity 1
- The FDA drug label for levofloxacin confirms that while E. faecalis is listed among organisms against which levofloxacin has activity, resistance can develop through mutations in defined regions of DNA gyrase or topoisomerase IV (Quinolone-Resistance Determining Regions) or through altered efflux mechanisms 2
Resistance Development and Clinical Implications
- Studies show that E. faecalis can rapidly develop resistance to fluoroquinolones during treatment, with resistance rates to levofloxacin reported at 4.8% to as high as 47% in different clinical settings 3, 4
- The mechanism of fluoroquinolone resistance in E. faecalis involves spontaneous mutations that occur at frequencies of 10^-9 to 10^-10, but these accumulate during treatment exposure 2
- Time-kill studies demonstrate that while levofloxacin can initially suppress E. faecalis growth, complete eradication is difficult to achieve, particularly with fluoroquinolone-resistant strains 5
Treatment Considerations
- For serious E. faecalis infections like endocarditis, guidelines recommend combination therapy rather than fluoroquinolone monotherapy, typically using a cell wall-active agent (ampicillin or vancomycin) plus an aminoglycoside 6
- When E. faecalis demonstrates resistance to multiple drugs, specialists in infectious diseases should be consulted to guide therapy 6
- For urinary tract infections caused by E. faecalis, ampicillin/sulbactam is recommended over ciprofloxacin in patients with risk factors for fluoroquinolone resistance 4
Clinical Pitfalls and Caveats
- Empiric fluoroquinolone monotherapy for suspected E. faecalis infections may lead to treatment failure due to the organism's natural low susceptibility and rapid mutation potential 4
- The slow killing rate of fluoroquinolones against E. faecalis may create a false impression of clinical improvement while allowing for the selection of resistant mutants 1
- Hospital-acquired infections, treatment in urological departments, and transfer from healthcare centers significantly increase the risk of ciprofloxacin-resistant E. faecalis (odds ratios of 18.15,6.15, and 7.39 respectively) 4
In clinical practice, when treating serious E. faecalis infections, combination therapy is preferred over fluoroquinolone monotherapy to prevent treatment failure and reduce the risk of developing resistance 6.