Treatment of Enterococcus faecium UTI
For uncomplicated lower urinary tract infections caused by E. faecium, initiate oral nitrofurantoin or fosfomycin as first-line therapy, while complicated or upper tract infections require parenteral linezolid or daptomycin due to the intrinsic penicillin resistance and high rates of vancomycin resistance in E. faecium. 1, 2
Critical Species Distinction
E. faecium is fundamentally different from E. faecalis and requires distinct treatment approaches. E. faecium exhibits intrinsic penicillin resistance, making ampicillin ineffective as first-line therapy, whereas E. faecalis typically remains ampicillin-susceptible 2. Up to 95% of E. faecium strains express multidrug resistance to vancomycin, aminoglycosides, and penicillins 2. This contrasts sharply with E. faecalis, where only 3% of strains are multidrug-resistant 2.
Uncomplicated Lower UTI (Cystitis)
Oral Treatment Options
Nitrofurantoin is FDA-approved for lower urinary tract infections and has good in vitro activity against vancomycin-resistant enterococci (VRE), including E. faecium 1. This agent achieves high urinary concentrations and is appropriate for uncomplicated cystitis 3, 4.
Fosfomycin is FDA-approved for UTI caused by E. faecalis and has in vitro activity against VRE infections, including E. faecium 1. Limited retrospective observational studies showed promising results in treating uncomplicated urinary tract infections due to VRE 1. In vitro studies demonstrate synergistic or additive effects when combined with linezolid, tigecycline, or gentamicin 1.
Doxycycline has intrinsic activity against enterococci including VRE and represents a possible oral option for VRE cystitis 4.
Treatment Duration
- 7-14 days for uncomplicated infections 2
Complicated UTI or Pyelonephritis
Parenteral First-Line Options
Linezolid 600 mg IV/PO every 12 hours is the preferred agent for vancomycin-resistant E. faecium with proven clinical efficacy 2, 5. The FDA label specifically indicates linezolid for vancomycin-resistant E. faecium infections, including cases with concurrent bacteremia 5. In an emergency-use protocol, linezolid achieved a 92.6% response rate across various VRE infection sites 6. A randomized trial comparing high-dose (600 mg every 12 hours) versus low-dose linezolid showed a 67% cure rate with the higher dose 6.
Daptomycin 8-12 mg/kg/day IV is an alternative option for vancomycin-resistant E. faecium 2, 7. The FDA label confirms activity against E. faecium, including vancomycin-resistant isolates 7. Daptomycin exhibits rapid, concentration-dependent bactericidal activity against Gram-positive bacteria 7. Case reports demonstrate effectiveness for complicated VRE UTIs, with rapid clinical improvement within 24 hours 8.
Important Pharmacokinetic Considerations
Tigecycline should NOT be used for VRE bacteremia or upper UTI due to large volume of distribution and low serum levels, despite being recommended for intra-abdominal VRE infections 1. This is a critical pitfall to avoid.
Treatment Duration
- 7-14 days for complicated UTI (14 days for males when prostatitis cannot be excluded) 1
- Minimum 4-6 weeks for bacteremia or endocarditis 2
Empiric Therapy Considerations
For patients with complicated UTI and systemic symptoms requiring empiric coverage, broad-spectrum therapy against Enterobacteriaceae and Enterococci should be initiated 1. The 2024 European Association of Urology guidelines recommend combinations such as:
- Amoxicillin plus aminoglycoside
- Second-generation cephalosporin plus aminoglycoside
- Third-generation cephalosporin 1
Antibiotic de-escalation must be implemented once culture results are available to narrow therapy based on susceptibilities and avoid selecting resistant pathogens 1.
Critical Pitfalls to Avoid
Never use cephalosporins alone for enterococcal coverage, as they have no intrinsic activity against enterococci 2. This is a common error in empiric therapy.
Do not assume E. faecium has the same susceptibility profile as E. faecalis - E. faecium requires different empiric coverage due to intrinsic penicillin resistance 2.
Avoid vancomycin for empiric E. faecium coverage given the 95% resistance rate 2.
Do not treat asymptomatic bacteriuria with multidrug-resistant Enterococcus - treatment is not recommended 3. It is essential to differentiate colonization from true infection prior to prescribing anti-VRE antimicrobial agents 1.
Adjunctive Measures
Remove indwelling urinary catheters when possible, as catheterization duration is the most important risk factor for catheter-associated UTI development 1, 3.
Always obtain urine culture and susceptibility testing to guide definitive therapy 1, 4.
Alternative Agents (Limited Data)
Quinupristin-dalfopristin has activity against E. faecium (MIC₉₀ = 2 mcg/ml) but NOT E. faecalis 6. Clinical response rates of 70.5% were observed in emergency-use programs, but myalgia/arthralgia frequently limits therapy 6. This agent should be evaluated case-by-case due to toxicity concerns 4.
Ampicillin at high doses (18-30 g IV daily) may overcome high ampicillin MIC in ampicillin-resistant VRE for urinary tract infections due to high urinary concentrations 1. One retrospective study reported 88.1% clinical eradication and 86% microbiological eradication in ampicillin-resistant VRE UTI treated with ampicillin 1. However, this approach remains controversial and should not be first-line for E. faecium given intrinsic resistance patterns 2.