What are the typical treatments for infections caused by urease-positive bacteria, such as Proteus, Klebsiella, and Pseudomonas species?

Treatment of Infections Caused by Urease-Positive Bacteria

For infections caused by urease-positive bacteria such as Proteus, Klebsiella, and Pseudomonas species, treatment should be tailored based on infection site, severity, and local resistance patterns, with aminoglycosides and beta-lactams being the cornerstone therapies for most serious infections. 1, 2

Common Urease-Positive Bacteria

• Proteus species (particularly P. mirabilis) - nearly 95% are urease positive 3
• Klebsiella species - approximately 98.5% are urease positive 3, 4
• Pseudomonas species - variable urease positivity 3
• Some Enterobacter species - less commonly urease positive 5, 4
• Staphylococcus species (some strains) 6

Clinical Significance of Urease Activity

• Urease-producing organisms convert urea to ammonia, raising urine pH 7, 8
• Associated with formation of struvite and calcium phosphate stones 6
• Can cause catheter encrustation and blockage 7
• Polymicrobial infections with urease-positive organisms show enhanced urease activity and increased disease severity 8
• P. mirabilis is significantly associated with catheter obstructions 7

Treatment Approaches by Infection Site

1. Urinary Tract Infections

For Complicated UTIs (including catheter-associated):

• First-line empiric therapy options: 7

  • Fluoroquinolones (if local resistance <10%)
  • Third-generation cephalosporins
  • Aminoglycosides (gentamicin, tobramycin)
  • Beta-lactam/beta-lactamase inhibitor combinations

• For severe infections or suspected multidrug-resistant strains: 7

  • Carbapenems (meropenem)
  • Ceftolozane/tazobactam
  • Ceftazidime/avibactam
  • Meropenem-vaborbactam

• Treatment duration: 7-14 days (14 days for men when prostatitis cannot be excluded) 7

2. Respiratory Tract Infections

• For community-acquired pneumonia with suspected Pseudomonas: 7

  • Antipneumococcal, antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either:
    • Ciprofloxacin or levofloxacin (750-mg dose), OR
    • An aminoglycoside plus azithromycin

• For penicillin-allergic patients: Substitute aztreonam for the beta-lactam 7

3. Intra-abdominal Infections

• For community-acquired infections of mild-to-moderate severity: 7

  • Ticarcillin-clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as single agents
  • OR combinations of metronidazole with cefazolin, cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin

• For healthcare-associated or severe infections: 7

  • Carbapenems
  • Piperacillin-tazobactam
  • Ceftazidime or cefepime plus metronidazole

4. Endocarditis and Bloodstream Infections

• For Gram-negative bacillary endocarditis: 7

  • Combination therapy with beta-lactam and aminoglycoside
  • For susceptible E. coli or Proteus mirabilis: ampicillin (2 g IV every 4 hours) or penicillin (20 million U IV daily) with gentamicin (1.7 mg/kg every 8 hours)
  • For Klebsiella: third-generation cephalosporin plus aminoglycoside
  • For Pseudomonas: antipseudomonal beta-lactam plus aminoglycoside

• Treatment duration: Prolonged course (4-6 weeks) with cardiac surgery often required 7

Special Considerations for Catheter-Associated Infections

• Catheter removal or replacement is recommended when possible 7
• Routine addition of antimicrobials or antiseptics to drainage bags is not recommended 7
• Catheter blockage from encrustation is common with urease-positive organisms, particularly P. mirabilis 7
• Bladder irrigation has not been shown to be effective for preventing catheter-associated bacteriuria in long-term catheterized patients 7

Monitoring and Follow-up

• Obtain cultures before initiating therapy when possible 1, 2
• Monitor urine pH in urinary tract infections (alkaline urine suggests urease activity) 6, 8
• Adjust therapy based on culture and susceptibility results 1
• For recurrent UTIs with urease-positive organisms, evaluate for urinary stones 6

Pitfalls and Caveats

• Bacteria within stones may differ from those in urine cultures, complicating treatment 6
• Polymicrobial infections with urease-positive organisms may have enhanced virulence 8
• Increasing resistance to commonly used antibiotics, including fluoroquinolones and beta-lactams, requires careful consideration of local resistance patterns 7
• Aminoglycosides require monitoring of drug levels and renal function 1
• Catheter biofilms may protect bacteria from antibiotic activity, necessitating catheter removal in persistent infections 7