Is linezolid active against Enterococcus faecalis biofilms?

Linezolid Activity Against Enterococcus faecalis Biofilms

Linezolid has limited activity against Enterococcus faecalis biofilms, requiring extremely high concentrations (MBIC90 of 4096 mg/L) to inhibit biofilm growth, which are not achievable with standard dosing in clinical practice. 1

Effectiveness of Linezolid Against E. faecalis Biofilms

• Linezolid is recommended for treatment of enterococcal infections, particularly vancomycin-resistant enterococci, but has poor activity against established E. faecalis biofilms 2
• In vitro studies demonstrate that extremely high concentrations of linezolid (MBIC90 of 4096 mg/L) are required to inhibit enterococcal biofilms, which are far above clinically achievable levels 1
• Tolerance to linezolid was observed in 93% of E. faecalis isolates in biofilm form, indicating significantly reduced susceptibility compared to planktonic (free-floating) bacteria 1

Combination Therapy Approaches for E. faecalis Biofilms

• Combining linezolid with rifampicin significantly improves activity against E. faecalis biofilms, reducing the minimum biofilm eradication concentrations (MBECs) to 16-32 mg/L 3
• The combination of linezolid and rifampicin was the second most effective combination (after ciprofloxacin plus rifampicin) in reducing bacterial counts in E. faecalis biofilms 3
• Rifampicin must always be combined with a second agent like linezolid to reduce the likelihood of resistance emergence when treating biofilm infections 4

Mechanisms of Reduced Linezolid Activity Against Biofilms

• Transcriptomic analysis of linezolid-resistant E. faecalis strains shows significant upregulation of genes associated with biofilm formation, suggesting biofilms contribute to reduced linezolid susceptibility 5
• Biofilm formation in E. faecalis is associated with upregulation of efflux pumps, which may contribute to linezolid resistance 5
• The G2576U mutation in 23S rRNA has been identified in linezolid-resistant E. faecalis isolates, with the number of mutated gene copies correlating with resistance level 6

Clinical Implications for Treatment of E. faecalis Biofilm Infections

• For implant-associated infections with E. faecalis biofilms, thorough debridement is essential before antibiotic therapy to reduce bacterial load 4
• For prosthetic joint infections caused by E. faecalis, linezolid is listed as a potential oral antibiotic option with excellent bioavailability, though its toxicity profile may limit long-term use 2
• For catheter-related bloodstream infections with E. faecalis biofilms, catheter removal is often necessary as antibiotic therapy alone may be insufficient 4
• If catheter retention is necessary in enterococcal infections, antibiotic lock therapy should be used in addition to systemic therapy 4

Important Considerations and Limitations

• Long-term linezolid use is limited by toxicity concerns including myelosuppression, peripheral and optic neuropathy, and lactic acidosis 4
• Resistance to linezolid can develop in E. faecalis after prolonged therapy (>30 days), necessitating susceptibility testing for patients with prior linezolid exposure 7
• No correlation between minimum biofilm inhibitory concentration (MBIC) and clinical outcome has been established for enterococcal biofilm infections 1
• For vancomycin-resistant E. faecalis biofilms, linezolid remains one of the few available treatment options despite its limitations 2