Treatment of VRE and ESBL Urinary Tract Infections
VRE Urinary Tract Infections
For uncomplicated VRE cystitis, use fosfomycin 3g PO as a single dose or nitrofurantoin 100mg PO every 6 hours for 5 days as first-line therapy. 1
First-Line Oral Options for Uncomplicated VRE Cystitis
- Fosfomycin 3g PO single dose is the most convenient option with excellent urinary concentrations 1, 2
- Nitrofurantoin 100mg PO every 6 hours for 5 days provides sustained urinary activity against VRE 1, 2
- High-dose ampicillin 18-30g IV daily in divided doses or amoxicillin 500mg PO/IV every 8 hours if ampicillin-susceptible 1, 2
Complicated VRE UTI or Pyelonephritis
For complicated VRE UTI or suspected upper tract infection, use linezolid 600mg IV or PO every 12 hours. 1, 3
- Linezolid achieves excellent urinary concentrations and has strong evidence with cure rates of 67% in high-dose regimens 1, 3
- Treatment duration should be 10-14 days for pyelonephritis 1
- FDA-approved specifically for VRE infections with demonstrated efficacy in clinical trials 3
Alternative for Complicated VRE UTI
- Daptomycin 8-12mg/kg IV daily is reserved for bacteremic VRE UTI or when linezolid cannot be used 1, 4
- Higher doses (10-12mg/kg) are preferred for serious infections 4
- Monitor creatine kinase levels with high-dose daptomycin 5
Critical Pitfall to Avoid
- Never use tigecycline for VRE bacteremia or suspected upper tract infection due to poor serum concentrations despite large volume of distribution 5, 2
ESBL Urinary Tract Infections
For uncomplicated ESBL cystitis, use nitrofurantoin 100mg PO every 6 hours for 5 days, fosfomycin 3g PO single dose, or pivmecillinam 400mg PO every 8 hours for 5 days. 6, 7, 8
First-Line Oral Options for Uncomplicated ESBL Cystitis
- Nitrofurantoin 100mg PO every 6 hours for 5 days shows 93-96% sensitivity against ESBL E. coli 6, 8
- Fosfomycin 3g PO single dose demonstrates 95-98% sensitivity against ESBL E. coli 6, 8
- Pivmecillinam 400mg PO every 8 hours for 5 days (where available) shows excellent activity with 95-96% sensitivity 7, 8
Complicated ESBL UTI or Pyelonephritis - Parenteral Options
For complicated ESBL UTI requiring IV therapy, use ertapenem 1g IV daily or piperacillin-tazobactam 3.375g IV every 6 hours (for E. coli only). 6, 7
- Carbapenems (ertapenem, meropenem, imipenem) remain highly effective but should be reserved for confirmed ESBL infections to preserve their utility 6, 7
- Piperacillin-tazobactam 3.375-4.5g IV every 6 hours is effective for ESBL E. coli (not Klebsiella) in mild-moderate infections 6, 7
- Ceftazidime-avibactam 2.5g IV every 8 hours or ceftolozane-tazobactam 1.5g IV every 8 hours are carbapenem-sparing alternatives 6, 7
- Aminoglycosides (gentamicin 5-7mg/kg IV daily) can be used for susceptible isolates but require monitoring 6, 7
Oral Step-Down Therapy for ESBL Pyelonephritis
- After clinical improvement on IV therapy, transition to nitrofurantoin, fosfomycin, or pivmecillinam if susceptible and lower tract infection only 7, 8
- Amoxicillin-clavulanate 875mg PO every 12 hours may be used for ESBL E. coli if MIC ≤8 mg/L 7
Critical Considerations for ESBL Treatment
- Avoid fluoroquinolones for empiric therapy due to high resistance rates (>30%) in ESBL-producing organisms 6, 7
- Avoid cephalosporins (except cefepime, ceftazidime-avibactam, ceftolozane-tazobactam) as ESBLs confer resistance to most cephalosporins 6, 7
- For Klebsiella ESBL UTI, nitrofurantoin has lower activity (42% sensitivity) compared to pivmecillinam (83%) and fosfomycin (62%) 8