Linezolid Dosing for Complicated UTI with Enterococcus
For complicated urinary tract infections caused by Enterococcus sensitive to linezolid, administer linezolid 600 mg IV or PO every 12 hours for 5-7 days. 1
Standard Dosing Regimen
- Linezolid 600 mg every 12 hours (IV or oral) is the recommended dose for complicated UTIs caused by Enterococcus, including vancomycin-resistant strains 1, 2
- Both intravenous and oral formulations achieve equivalent therapeutic concentrations and can be used interchangeably 1
- The standard duration is 5-7 days for complicated UTIs, though this should be extended based on clinical response 1
Evidence Supporting This Dosing
- The FDA-approved dosing for vancomycin-resistant enterococcal infections is 600 mg every 12 hours, which achieved cure rates of 67% in the intent-to-treat population 2
- For urinary tract infections specifically, the cure rate was 63% (12/19 patients) in the FDA registration trial 2
- Clinical data demonstrates overall microbiological and clinical cure rates of 86.4% and 81.4% respectively for VRE infections with this dosing regimen 1
Pharmacokinetic Considerations
- Linezolid achieves approximately 40-44% renal excretion of the parent drug, providing adequate urinary concentrations 3
- The 600 mg twice daily regimen maintains plasma concentrations above the MIC for the entire dosing interval and achieves an AUC/MIC ratio >100, which are the key pharmacodynamic targets 4
- Bactericidal titers in urine with 600 mg dosing show median dilutions of 1:96 for enterococcal strains within the first 6 hours 3
Important Caveats
- Do not increase the dose beyond 600 mg every 12 hours for standard complicated UTIs, as higher doses (such as 600 mg every 8 hours or continuous infusion) significantly increase the risk of hematologic toxicity (Ctrough ≥9 μg/mL associated with toxicity) 5
- The standard 1,200 mg/day total dose is optimal for Enterococcus isolates with linezolid MICs ≤1 μg/mL 5
- For isolates with MIC of 2 μg/mL, consider combination therapy rather than dose escalation to avoid toxicity while achieving therapeutic targets 5
Special Populations
- Critically ill patients or those on continuous venovenous hemofiltration (CVVH): Maintain the standard 600 mg every 12 hours dosing, as linezolid pharmacokinetics remain comparable despite renal replacement therapy 6
- Pediatric patients <12 years: Use 10 mg/kg/dose every 8 hours, not to exceed 600 mg/dose 7
- Pediatric patients ≥12 years: Use adult dosing of 600 mg every 12 hours 7
Clinical Outcomes Data
- Real-world effectiveness data shows linezolid performs comparably to other VRE-active antibiotics for urinary tract infections, with no significant differences in re-initiation of antibiotics (9% vs 5%), recurrent positive cultures (4% vs 11%), or mortality (7% vs 3%) 8
- Most treatment failures are due to asymptomatic bacteriuria being inappropriately treated rather than true linezolid failure 8