What is the recommended treatment for a patient with a urinary tract infection (UTI) caused by Pseudomonas aeruginosa and chronic kidney disease (CKD)?

Treatment of Pseudomonas aeruginosa UTI in Chronic Kidney Disease

For a patient with Pseudomonas aeruginosa UTI and CKD, use ceftolozane-tazobactam or ceftazidime-avibactam as first-line therapy, with meropenem 1 gram IV every 8 hours (dose-adjusted for renal function) as an alternative, avoiding aminoglycosides and fluoroquinolones due to nephrotoxicity concerns in this population. 1, 2

First-Line Parenteral Therapy

Novel beta-lactam/beta-lactamase inhibitor combinations are the preferred agents for Pseudomonas aeruginosa UTI in CKD patients:

• Ceftolozane-tazobactam is recommended for difficult-to-treat Pseudomonas aeruginosa (DTR-PA) infections, showing better cure rates and less acute kidney injury compared to polymyxin or aminoglycoside-based regimens 1
• Ceftazidime-avibactam 2.5 g IV every 8 hours (infused over 3 hours) is an alternative option with activity against carbapenem-resistant Pseudomonas aeruginosa (CRPA) 1
• Imipenem-cilastatin-relebactam is active against most CRPA strains and represents another treatment option 1

Carbapenem Therapy with Renal Dose Adjustment

When novel agents are unavailable or based on susceptibility testing, meropenem remains an option with mandatory dose adjustment:

• For Pseudomonas aeruginosa infections, meropenem 1 gram IV every 8 hours is the recommended dose in patients with normal renal function 2
• Dose adjustment is critical in CKD: For CrCl 26-50 mL/min, give the recommended dose every 12 hours; for CrCl 10-25 mL/min, give one-half the recommended dose every 12 hours; for CrCl <10 mL/min, give one-half the recommended dose every 24 hours 2
• Meropenem can be administered as a 15-30 minute infusion or as a 3-5 minute bolus injection 2

Agents to Avoid in CKD Patients

Aminoglycosides should be used with extreme caution or avoided entirely in CKD patients with Pseudomonas UTI:

• While aminoglycosides achieve excellent urinary concentrations (25- to 100-fold above plasma levels) and maintain activity against many uropathogens, they pose significant nephrotoxicity risk 1
• If aminoglycosides must be used, close monitoring of creatinine clearance and electrolytes is mandatory 3
• Plazomicin, a novel aminoglycoside with lower nephrotoxicity (16.7% vs 50% acute renal injury compared to colistin), may be considered but evidence is limited 1

Fluoroquinolones have limited utility in this population:

• Ciprofloxacin historically showed only 44% bacteriological cure rates in chronic Pseudomonas UTI with functional/anatomical abnormalities, with relapse occurring in 44% of cases 4
• Resistance development during therapy is a concern, occurring in approximately 30% of treatment failures 5
• Fluoroquinolones should only be used when local resistance is <10% and require careful dose adjustment in CKD 1, 3

Treatment Duration and Monitoring

Treatment duration should be 7-14 days based on clinical response and underlying factors:

• Minimum 7 days for uncomplicated presentations that respond rapidly (afebrile within 48 hours) 1
• 14 days when prostatitis cannot be excluded (relevant for male patients) or when underlying urological abnormalities are present 1, 6
• Monitor renal function closely during therapy, particularly with agents requiring dose adjustment 1, 3

Antimicrobial Susceptibility Testing is Mandatory

Always obtain urine culture and susceptibility testing before initiating therapy:

• Pseudomonas aeruginosa resistance patterns vary significantly by institution and region 1, 7
• Recent data shows high resistance to beta-lactams (84-94%) but preserved susceptibility to carbapenems, polymyxins, and novel agents 7
• Antimicrobial susceptibility testing of novel beta-lactam/beta-lactamase inhibitors is specifically recommended to guide treatment of CRPA infections 1

Address Underlying Urological Abnormalities

Optimal antimicrobial therapy alone is insufficient without addressing complicating factors:

• Obstruction, incomplete voiding, foreign bodies (catheters), or vesicoureteral reflux must be identified and managed 1
• Pseudomonas aeruginosa is particularly associated with complicated UTIs and healthcare-associated infections 1
• Failure to address anatomical/functional abnormalities leads to treatment failure and recurrence 1

Common Pitfalls to Avoid

• Do not use standard dosing of renally-cleared antibiotics without calculating creatinine clearance - this leads to drug accumulation and toxicity 3
• Do not rely on serum creatinine alone when using trimethoprim - it artificially elevates creatinine by blocking tubular secretion without actual GFR decline; use 24-hour urine collection if needed 3
• Do not use polymyxin-based therapy as first-line when novel agents are available - polymyxins carry 50% acute kidney injury risk in CKD patients 1
• Do not treat for less than 7 days - inadequate duration leads to persistence and recurrence, particularly with Pseudomonas 1, 4