Does a patient with a complicated urinary tract infection caused by Carbapenem-resistant Pseudomonas aeruginosa (CRPA) require intravenous (IV) antibiotics?

Treatment of Complicated UTI Caused by CRPA: IV vs Oral Antibiotics

Yes, IV antibiotics are required for complicated urinary tract infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA), with the specific route and agent determined by infection severity and susceptibility testing. 1, 2

Treatment Algorithm Based on Severity

For Severe or Complicated CRPA UTI

• First-line treatment is ceftolozane-tazobactam 1.5 g IV every 8 hours if the isolate is susceptible in vitro 1, 2
• Alternative IV agents include imipenem-relebactam, cefiderocol, or ceftazidime-avibactam based on susceptibility, though evidence remains limited 1, 2
• If newer beta-lactam/beta-lactamase inhibitors are unavailable or the organism is resistant, use combination therapy with two IV active agents (polymyxin plus aminoglycoside, polymyxin plus fosfomycin, or polymyxin plus carbapenem if meropenem MIC ≤8 mg/L) 1, 2, 3

For Non-Severe CRPA UTI

• Monotherapy with an older antibiotic active in vitro is acceptable, chosen based on individual susceptibility testing 1, 2
• Acceptable options include aminoglycosides (gentamicin, amikacin, plazomicin), fluoroquinolones (ciprofloxacin, levofloxacin), or polymyxins (colistin) if susceptible 2
• Single-dose aminoglycoside is highly effective for uncomplicated cystitis, with microbiologic cure rates of 87-100% due to urinary concentrations exceeding peak plasma levels by 25- to 100-fold 2
• Research supports that aminoglycoside or colistin monotherapy shows good efficacy and safety for complicated UTI caused by extensively drug-resistant Pseudomonas aeruginosa 4

Route of Administration Considerations

When IV Route is Mandatory

• The IV route is preferable for patients with bacterial septicemia, severe or life-threatening infections, or those who are poor risks due to debilitating conditions (malnutrition, trauma, surgery, diabetes, heart failure, malignancy, or shock) 5
• Complicated UTI with systemic involvement requires IV therapy for 10-14 days 2

When Oral/IM May Be Considered

• For non-severe infections without systemic involvement, certain agents like aminoglycosides can be given IM 5
• Oral fosfomycin (3 grams every 48-72 hours for 3 doses) has been used off-label for complicated lower UTI caused by MDR pathogens, particularly in patients who failed other treatments 6
• However, oral options are generally not recommended as first-line for CRPA complicated UTI given the severity and resistance profile 1, 2

Critical Dosing and Management Principles

• Prolonged or extended infusions of beta-lactams are recommended when treating pathogens with high MICs to optimize pharmacodynamic targets 1, 2
• Therapeutic drug monitoring is strongly suggested for polymyxins, aminoglycosides, and carbapenems, especially in critically ill patients 2, 3
• Infectious disease consultation is highly recommended for all CRPA infections 1, 2, 3
• Obtain antimicrobial susceptibility testing before finalizing therapy, as local resistance patterns vary significantly 2, 3

Common Pitfalls to Avoid

• Never use polymyxin monotherapy for severe CRPA infections—it is associated with higher treatment failure rates 2, 3
• Avoid tigecycline for CRPA bacteremia—serum concentrations are inadequate for bloodstream infections 3
• Avoid carbapenem-based therapy unless meropenem MIC is ≤8 mg/L with high-dose extended infusion 1, 2
• Do not use polymyxin-rifampin combinations—there is no evidence supporting this regimen for CRPA 3

Treatment Duration

• Complicated UTI without systemic involvement: 5-10 days 2
• Pyelonephritis or UTI with bacteremia: 10-14 days 2
• Duration should be adjusted based on source control, clinical response, and underlying comorbidities 2