Treatment of Pseudomonas and Enterococcus UTI
For a polymicrobial UTI with both Pseudomonas and Enterococcus, initiate empiric broad-spectrum therapy with cefepime 2g IV every 8-12 hours or piperacillin-tazobactam 3.375-4.5g IV every 8 hours, which provides coverage for both pathogens, then narrow therapy based on culture susceptibilities within 48-72 hours. 1, 2
Initial Empiric Therapy Selection
Start with broad-spectrum coverage immediately while awaiting culture results, as dual-pathogen UTIs require agents active against both organisms 3:
- Cefepime 2g IV every 8-12 hours is FDA-approved for complicated UTIs and covers both Pseudomonas aeruginosa and many Enterococcus species (though not VRE) 2
- Piperacillin-tazobactam 2.5-4.5g IV every 8 hours provides excellent coverage for Pseudomonas and ampicillin-susceptible Enterococcus 3, 1
- Add ampicillin 2g IV every 6 hours if high suspicion for Enterococcus and not using piperacillin-tazobactam, as cefepime has limited enterococcal activity 1
Culture-Directed Therapy Adjustments
Obtain urine culture before starting antibiotics and adjust therapy within 48-72 hours based on susceptibilities 3:
For Pseudomonas aeruginosa:
- Fluoroquinolones (ciprofloxacin 400mg IV every 12 hours or levofloxacin 750mg IV daily) if susceptible 1, 4
- Ceftazidime or cefepime if beta-lactam susceptible 5
- Aminoglycosides (gentamicin 5mg/kg IV every 24 hours or amikacin 15mg/kg IV every 24 hours) for resistant strains 1, 5
For Enterococcus species:
- Ampicillin 2g IV every 6 hours for ampicillin-susceptible strains 6
- Nitrofurantoin 100mg PO twice daily for uncomplicated lower UTI with susceptible strains 6
- Fosfomycin 3g PO single dose for uncomplicated cystitis, including VRE 6, 7
- Linezolid 600mg IV/PO every 12 hours or daptomycin 6-8mg/kg IV daily for VRE in complicated/upper tract infections 6
Duration of Treatment
Treat for 7-14 days depending on clinical severity and response 3:
- 7 days for patients with prompt symptom resolution and uncomplicated course 3
- 10-14 days for delayed response, upper tract involvement, or critically ill patients 3
- 3-5 days may be sufficient if adequate source control achieved and patient clinically improving 3
Critical Management Considerations
Remove or replace indwelling urinary catheters when feasible, as biofilms harbor both organisms and prevent antibiotic penetration 3:
- If catheter present >2 weeks, replace before initiating antibiotics to improve treatment response 3
- Obtain culture from freshly placed catheter for accurate susceptibility data 3
Dose adjust for renal function, particularly critical with aminoglycosides and beta-lactams 3:
- Cefepime requires dose reduction when CrCl <60 mL/min 2
- Monitor renal function closely with aminoglycosides to prevent nephrotoxicity 1
Avoid treating asymptomatic bacteriuria even with these organisms present, as treatment increases resistance without clinical benefit 3
Resistance Considerations
For carbapenem-resistant Enterobacteriaceae (if present), escalate to newer agents 1, 5:
- Ceftazidime-avibactam 2.5g IV every 8 hours for 5-7 days 1
- Meropenem-vaborbactam 4g IV every 8 hours 1
- Imipenem-cilastatin-relebactam 1.25g IV every 6 hours 1
For multidrug-resistant Pseudomonas, consider combination therapy with two active agents from different classes to prevent treatment failure 5, 8
Common Pitfalls to Avoid
- Do not use fluoroquinolones empirically if patient has recent fluoroquinolone exposure or local resistance rates exceed 10% 3, 5
- Do not use cephalosporins alone for Enterococcus as they have poor activity; always add ampicillin or alternative enterococcal coverage 6
- Do not continue empiric broad-spectrum therapy beyond 72 hours without culture confirmation; narrow based on susceptibilities to reduce resistance pressure 3
- Do not classify as "complicated UTI" solely based on dual organisms; reserve this designation for structural abnormalities, immunosuppression, or catheter-associated infections 3