From the Guidelines
Linezolid is the preferred treatment for vancomycin-resistant enterococci (VRE) infections, with a standard dosing of 600 mg twice daily, either orally or intravenously, as recommended by the most recent guidelines 1. The treatment duration typically ranges from 7-14 days for uncomplicated infections, but may extend to 4-6 weeks for more severe infections like endocarditis or osteomyelitis. Key points to consider when using linezolid include:
- Monitoring for potential adverse effects, including myelosuppression (particularly thrombocytopenia), which typically occurs after 2 weeks of therapy, peripheral and optic neuropathy with prolonged use, and serotonin syndrome when combined with serotonergic medications 1.
- Complete blood counts should be monitored weekly, especially for treatments longer than 14 days.
- For patients unable to tolerate linezolid, alternatives include daptomycin (though resistance can develop), tigecycline, or quinupristin-dalfopristin, depending on the infection site and susceptibility patterns. Some of the key recommendations from the guidelines include:
- Linezolid 600 mg IV or PO every 12 h is recommended for enterococcal infections, with the treatment duration dependent on the site of infection and clinical response (Strong recommendation, low quality of evidence) 1.
- High dose daptomycin 8-12 mg/kg/day or in combination with beta-lactams is recommended for VRE bacteremia (Weak recommendation, low quality of evidence) 1.
- Tigecycline 100 mg IV loading dose then 50 mg IV q12 h is recommended for intra-abdominal infections due to VRE (Weak recommendation, very low quality of evidence) 1.
From the FDA Drug Label
1.5 Vancomycin-resistant Enterococcus faecium Infections Linezolid is indicated for the treatment of vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia [see Clinical Studies (14)].
The role of Linezolid in treating Vancomycin-Resistant Enterococci (VRE) infections is that it is indicated for the treatment of vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia 2.
- Key points:
- Linezolid is effective against vancomycin-resistant Enterococcus faecium.
- It can be used to treat infections with concurrent bacteremia.
- The safety and efficacy of linezolid for this indication are supported by clinical studies.
From the Research
Role of Linezolid in Treating VRE Infections
- Linezolid is an oxazolidinone antibiotic that has inhibitory activity against a broad range of gram-positive bacteria, including vancomycin-resistant enterococci (VRE) 3.
- It has been shown to be effective in treating VRE infections, with a clinical response rate of 92.6% in one study 4.
- Linezolid works by inhibiting the bacterial pre-translational initiation complex formation, and has bacteriostatic activity against both vancomycin-resistant E. faecium and E. faecalis 4.
Efficacy of Linezolid in VRE Infections
- Studies have demonstrated that linezolid is as effective as vancomycin in eradicating infections caused by methicillin-resistant Staphylococcus spp. and has demonstrated efficacy against infections caused by VRE 3.
- A multicenter compassionate-use trial found that linezolid was effective in treating VRE infections in solid organ transplant recipients, with a clinical response rate of 62.4% and a survival rate of 62.4% 5.
- Another study found that linezolid was effective in treating VRE infections, with a cure rate of 67% in the high-dose group and 52% in the low-dose group 4.
Optimization of Linezolid Dosing Regimens
- A study found that a dosing regimen of 1,200 mg either once daily or as a divided dose every 12 h gave target attainments of fAUC24/MICs >80 and >100, which exceeded 90% for MICs ≤1 and ≤1 μg/mL, respectively, with a rate of hematologic toxicity <15% 6.
- The study also found that a 1,200-mg divided dose every 12 h could cover VRE isolates having linezolid MICs ≤1 μg/mL and ≤0.75 μg/mL, and that the current dosing of 1,200 mg/day might be optimal treatment for infection by VRE isolates with documented MICs ≤1 μg/mL 6.
Resistance to Linezolid
- Resistance to linezolid has been reported in a small number of E. faecium strains, which appears to be secondary to a base-pair mutation in the genome encoding for the bacterial 23S ribosome binding site 4.
- A study found that emergence of resistance to linezolid occurred rarely, but that susceptibility testing should be done in all cases on starting therapy 7.