Is Enterococcus faecalis sensitive to azithromycin (a macrolide antibiotic)?

Enterococcus faecalis Resistance to Azithromycin

Enterococcus faecalis is intrinsically resistant to azithromycin and should not be treated with this antibiotic. Based on clinical evidence, E. faecalis demonstrates poor susceptibility to macrolide antibiotics, including azithromycin 1.

Resistance Patterns and Mechanisms

Intrinsic Resistance

• E. faecalis shows high levels of resistance to azithromycin, with studies demonstrating only 14.2% of isolates being susceptible 1
• Macrolide resistance in enterococci is often intrinsic to the species, not just acquired through mutation or horizontal gene transfer 2

Resistance Mechanisms

• Many Gram-negative bacteria, including Enterobacteriaceae, show reduced permeability of their outer cell envelope to macrolides 3
• Enterococci commonly express resistance through:
  • Target-site modifications (erm genes) causing high-level resistance
  • Efflux mechanisms
  • Enzymatic inactivation 3, 4

Clinical Evidence of Resistance

A comprehensive study of E. faecalis isolates from root-filled teeth with periapical lesions found:

• Only 14.2% of E. faecalis isolates were susceptible to azithromycin
• 28.5% were susceptible to erythromycin (another macrolide)
• MICs for azithromycin were significantly higher than for other antibiotics 1

Another study examining E. faecium (related species) found 100% resistance to azithromycin among isolates 4.

Alternative Treatment Options

For infections caused by E. faecalis, the following antibiotics show better efficacy:

First-line options:

• Amoxicillin or ampicillin (100% susceptibility) 1
• Amoxicillin-clavulanic acid (100% susceptibility) 1
• Vancomycin (for penicillin-allergic patients) 1, 3

Second-line options:

• Moxifloxacin (100% susceptibility) 1
• Chloramphenicol (95.2% susceptibility) 1
• Tetracycline/doxycycline (85.7% susceptibility) 1
• Ciprofloxacin (80.9% susceptibility) 1

Special Considerations

For Serious Infections

• For enterococcal endocarditis, combination therapy with a cell-wall active agent (ampicillin, vancomycin) plus an aminoglycoside is recommended 3
• For β-lactamase-producing strains, ampicillin-sulbactam is effective 3

Vancomycin-Resistant Enterococci (VRE)

• For VRE infections, linezolid has shown 77% cure rates in endocarditis 3
• Quinupristin-dalfopristin may be effective against E. faecium but not E. faecalis (intrinsic resistance) 3

Clinical Pitfalls to Avoid

• Do not use macrolides empirically when enterococcal infection is suspected
• Do not rely on azithromycin for E. faecalis infections, even if the isolate appears susceptible in vitro, as clinical failure rates are high
• Be aware of increasing resistance patterns in enterococci to multiple antibiotics, requiring susceptibility testing before initiating therapy 2
• Consider combination therapy for serious enterococcal infections rather than monotherapy 3

In conclusion, azithromycin should not be used for treating E. faecalis infections due to intrinsic resistance patterns. Penicillins (amoxicillin, ampicillin) remain the most effective first-line agents, with vancomycin as an alternative for penicillin-allergic patients.