What antibiotics are effective for treating a urinary tract infection (UTI) caused by Enterococcus and Pseudomonas?

Treatment of Polymicrobial UTI with Enterococcus and Pseudomonas

For a UTI caused by both Enterococcus and Pseudomonas, you must treat both organisms simultaneously with combination therapy guided by susceptibility testing, prioritizing agents with dual coverage or using two separate antibiotics that address each pathogen's resistance profile.

Initial Management Approach

The critical first step is obtaining urine culture with susceptibility testing before initiating therapy, as both organisms have unpredictable resistance patterns that cannot be reliably covered empirically 1. Remove any indwelling urinary catheters immediately if present, as catheterization is a major risk factor for both enterococcal and pseudomonal UTIs 2, 3.

Empirical Therapy Options (While Awaiting Culture Results)

For complicated UTIs requiring immediate treatment:

Option 1: Fluoroquinolone-Based Regimen

• Levofloxacin 750 mg IV/PO daily provides coverage for both Enterococcus faecalis and Pseudomonas aeruginosa 1, 4
• This is FDA-approved for complicated UTIs caused by both Enterococcus faecalis and Pseudomonas aeruginosa 4
• Critical caveat: Local resistance rates must be <10% for fluoroquinolones, as resistance is increasingly common in both organisms 1, 2, 3
• Avoid if the patient received fluoroquinolones in the past 3 months 5

Option 2: Combination Therapy

• Ceftazidime 2g IV q8h (for Pseudomonas) PLUS ampicillin 2g IV q6h (for Enterococcus) if susceptibility is likely 1, 2
• Alternative: Piperacillin-tazobactam 4.5g IV q6h may provide coverage for both organisms if susceptibilities permit 1

Definitive Therapy (After Susceptibility Results)

For Pseudomonas Coverage:

If susceptible to standard agents:

• Ceftazidime 2g IV q8h 1
• Cefepime 2g IV q8-12h 1
• Piperacillin-tazobactam 4.5g IV q6h 1
• Ciprofloxacin 400mg IV q8h or levofloxacin 750mg IV daily 1, 4

If difficult-to-treat or carbapenem-resistant Pseudomonas:

• Ceftolozane-tazobactam 3g IV q8h (for pneumonia/severe infections) or 1.5g IV q8h 1
• Ceftazidime-avibactam 2.5g IV q8h 1
• Colistin-based combination therapy: 5mg CBA/kg IV loading dose, then 2.5mg CBA × (1.5 × CrCl + 30) IV q12h 1

For Enterococcus Coverage:

For uncomplicated lower UTI (cystitis):

• Fosfomycin 3g PO single dose (first-line for E. faecalis) 1, 2, 3
• Nitrofurantoin 100mg PO q6h for 5-7 days 1, 2, 3
• High-dose ampicillin 18-30g IV daily in divided doses or amoxicillin 500mg PO/IV q8h (if susceptible) 1, 2

For complicated UTI or pyelonephritis:

• Linezolid 600mg IV/PO q12h 1, 2, 3
• High-dose daptomycin 8-12 mg/kg IV daily (particularly for VRE) 1, 3
• Ampicillin (if susceptible) - high urinary concentrations may overcome resistance even in ampicillin-resistant strains 2, 3

Recommended Combination Regimens

For Susceptible Organisms:

• Levofloxacin 750mg IV/PO daily (covers both) for 7-10 days 1, 4
• Ceftazidime 2g IV q8h PLUS ampicillin 2g IV q6h for 7-10 days 1, 2

For Resistant Organisms:

• Ceftolozane-tazobactam 1.5-3g IV q8h PLUS linezolid 600mg IV q12h 1
• Ceftazidime-avibactam 2.5g IV q8h PLUS daptomycin 8-12mg/kg IV daily 1

Treatment Duration

• Uncomplicated lower UTI: 5-7 days 2, 3
• Complicated UTI: 7-10 days 1
• Pyelonephritis or bloodstream infection: 10-14 days 1

Critical Pitfalls to Avoid

• Never treat asymptomatic bacteriuria with these organisms, as this fosters resistance without clinical benefit 2, 3
• Do not use fluoroquinolones empirically if local resistance exceeds 10% or if the patient received them recently 1, 2, 5
• Avoid aminoglycoside monotherapy except for simple cystitis; they require combination therapy for complicated infections 1
• Do not assume susceptibility patterns - patients receiving antibiotics to which organisms are resistant have twice the risk of requiring additional prescriptions (34% vs 19%) and hospitalization (15% vs 8%) 5
• Tigecycline monotherapy is not recommended for UTIs despite in vitro activity 1
• Differentiate colonization from true infection before initiating therapy, especially in catheterized patients 2, 3

High-Risk Patient Considerations

Patients at increased risk of treatment failure requiring more aggressive initial therapy include 5:

• Age >60 years
• Diabetes mellitus
• Male sex
• Prior culture showing resistance to the antibiotic class being considered
• Recent antibiotic exposure within 3 months