From the Guidelines
For treating vancomycin-resistant enterococci (VRE) urinary tract infections, linezolid (600 mg orally twice daily for 7-14 days) or daptomycin (8-12 mg/kg IV once daily for 7-14 days) are recommended first-line options. Alternatives include quinupristin-dalfopristin, tigecycline, or fosfomycin, depending on susceptibility testing 1.
Key Considerations
- The treatment duration is dependent on the site of infection and clinical response, with a minimum of 7-14 days recommended for uncomplicated urinary tract infections 1.
- For fungal UTIs, which are most commonly caused by Candida species, fluconazole is the preferred treatment (loading dose of 800 mg followed by 400 mg daily for 14 days) 1.
- For fluconazole-resistant species like C. glabrata or C. krusei, an echinocandin such as caspofungin (70 mg loading dose, then 50 mg daily) or micafungin (100 mg daily) for 14 days is recommended 1.
- Amphotericin B deoxycholate (0.3-0.6 mg/kg daily for 1-7 days) can be used for severe cases 1.
- Source control is crucial in both infections, including removal or exchange of urinary catheters if present.
- Patients should complete the full course of therapy even if symptoms resolve quickly.
- Underlying conditions like diabetes or immunosuppression should be optimized, and follow-up urine cultures are recommended to confirm eradication of the infection.
Treatment Options for VRE UTI
- Linezolid: 600 mg orally twice daily for 7-14 days 1
- Daptomycin: 8-12 mg/kg IV once daily for 7-14 days 1
- Fosfomycin: 3 g PO single dose or 3 g PO every other day for uncomplicated urinary tract infections 1
- Nitrofurantoin: 100 mg PO every 6 hours for uncomplicated urinary tract infections 1
- High dose ampicillin: 18-30 g IV daily in divided doses or amoxicillin 500 mg PO/IV every 8 hours for uncomplicated urinary tract infections 1
From the FDA Drug Label
The cure rates for the ITT population with documented vancomycin-resistant enterococcal infection at baseline are presented in Table 15 by source of infection. These cure rates do not include patients with missing or indeterminate outcomes. The cure rate was higher in the high-dose arm than in the low-dose arm, although the difference was not statistically significant at the 0. 05 level. Table 15. Cure Rates at the Test-of-Cure Visit for ITT Adult Patients with Documented Vancomycin-Resistant Enterococcal Infections at Baseline Source of Infection Cured ZYVOX600 mg q12hn/N (%) ZYVOX200 mg q12hn/N (%)
- Includes sources of infection such as hepatic abscess, biliary sepsis, necrotic gall bladder, pericolonic abscess, pancreatitis, and catheter-related infection Any site 39/58 (67) 24/46 (52) Any site with associated bacteremia 10/17 (59) 4/14 (29) Bacteremia of unknown origin 5/10 (50) 2/7 (29) Skin and skin structure 9/13 (69) 5/5 (100) Urinary tract 12/19 (63) 12/20 (60) Pneumonia 2/3 (67) 0/1 (0) Other* 11/13 (85) 5/13 (39)
The treatment of VRE (vancomycin-resistant enterococcal) infections, including those in the urinary tract, with linezolid has been studied.
- The cure rates for VRE infections in the urinary tract were 63% for the 600 mg q12h dose and 60% for the 200 mg q12h dose.
- However, there is no information in the provided drug labels about the treatment of fungal UTI with linezolid.
- Linezolid is effective against certain Gram-positive bacteria, including VRE, but its effectiveness against fungal infections is not mentioned in the provided drug labels.
- Therefore, linezolid may be considered for the treatment of VRE UTI, but not for fungal UTI, based on the provided information 2.
From the Research
Treatment Options for Vancomycin-Resistant Enterococci (VRE)
- Available agents for treating VRE include chloramphenicol, doxycycline, high-dose ampicillin or ampicillin/sulbactam, and nitrofurantoin (for lower urinary tract infection) 3
- Two novel antimicrobial agents, quinupristin/dalfopristin and linezolid, have emerged as approved therapeutic options for vancomycin-resistant Enterococcus faecium 3
- Quinupristin/dalfopristin has bacteriostatic activity against vancomycin-resistant E. faecium, but is not active against Enterococcus faecalis 3
- Linezolid has bacteriostatic activity against both vancomycin-resistant E. faecium and E. faecalis 3
Linezolid Dosing Regimens for VRE Treatment
- 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% 4
- The current dosing of 1,200 mg/day might be optimal treatment for infection by VRE isolates with documented MICs ≤1 μg/mL 4
- For treatment of VRE with a MIC of 2 μg/mL or to achieve the target CFR, the use of linezolid with other antibiotic combinations might help achieve the PK/PD target, provide better clinical outcome, and prevent resistance 4
Comparison of Linezolid and Daptomycin for VRE Treatment
- Linezolid was associated with a significantly higher risk of treatment failure compared with daptomycin (risk ratio [RR], 1.37; 95% confidence interval [CI], 1.13-1.67; P = .001) 5
- Linezolid was also associated with higher 30-day mortality (42.9% vs 33.5%; RR, 1.17; 95% CI, 1.04-1.32; P = .014) and microbiologic failure rates (RR, 1.10; 95% CI, 1.02-1.18; P = .011) 5
- No difference in microbiologic and clinical cures between linezolid and daptomycin was found in a systematic review and meta-analysis (n = 5 studies, 517 patients; OR, 1.0; 95% CI, 0.4 to 1.7; P = 0.95) 6
Linezolid for Urinary Tract Infections Caused by VRE
- Linezolid appears effective as comparator antibiotics for the treatment of mild vancomycin-resistant Enterococcus urinary tract infection 7
- No difference between linezolid and comparator antibiotics were observed in re-initiation of antibiotics for vancomycin-resistant Enterococcus urinary tract infection, recurrent positive vancomycin-resistant Enterococcus culture, or mortality 7