What is the recommended treatment for a patient with a carbapenem-resistant urinary tract infection (UTI) and potential impaired renal function?

Treatment of Carbapenem-Resistant UTI with Renal Impairment

For carbapenem-resistant UTI in patients with potential renal impairment, use ceftazidime-avibactam 2.5 g IV every 8 hours with dose adjustment based on creatinine clearance, as this newer β-lactam/β-lactamase inhibitor combination provides superior outcomes while avoiding the nephrotoxicity associated with colistin and aminoglycosides. 1, 2, 3

Preferred First-Line Agents for Complicated CRE-UTI

Newer β-lactam/β-lactamase inhibitor combinations are the preferred agents for carbapenem-resistant Enterobacteriaceae (CRE) causing complicated UTI:

• Ceftazidime-avibactam 2.5 g IV every 8 hours infused over 2 hours is the primary recommendation, with proven efficacy showing 70.1% combined clinical and microbiological cure rates versus 54.0% with best available therapy 1, 2, 3

• Meropenem-vaborbactam 4 g IV every 8 hours is an equally preferred alternative for CRE-UTI 1, 2

• Imipenem-cilastatin-relebactam 1.25 g IV every 6 hours represents another first-line option 1, 2

• Plazomicin 15 mg/kg IV every 12 hours is recommended as a preferred newer aminoglycoside agent 1

Critical Renal Dosing Considerations

Dose adjustment is mandatory for patients with creatinine clearance <50 mL/min when using ceftazidime-avibactam 3:

• The standard dose of 2.5 g every 8 hours applies only to CrCl >50 mL/min 3

• Specific reduced dosing regimens exist for moderate to severe renal impairment (consult prescribing information for exact adjustments) 3

• This renal-sparing profile makes ceftazidime-avibactam superior to colistin, which carries a 29.4% acute kidney injury rate even in non-critically ill patients 4

Simple Cystitis Due to CRE: Different Approach

For uncomplicated lower UTI (simple cystitis) caused by CRE, the treatment strategy differs significantly:

• Single-dose aminoglycoside (amikacin or gentamicin) is the recommended first-line therapy 5, 1, 2

• This approach is supported by meta-analysis of 13,804 patients showing 87-100% microbiologic cure rates for lower UTI 1

• Aminoglycosides achieve urinary concentrations 25- to 100-fold higher than plasma levels, making them ideal for UTI despite systemic toxicity concerns 1, 2

Alternative Options When First-Line Agents Unavailable

If newer agents are not available or not susceptible, consider these alternatives with important caveats:

• IV fosfomycin for non-severe complicated UTI without septic shock 1

• Polymyxin-based (colistin) combination therapy based on susceptibility testing results 5

• Avoid tigecycline monotherapy for any bloodstream involvement due to suboptimal outcomes 1, 2

Common Pitfalls to Avoid

Nephrotoxicity monitoring is critical regardless of agent chosen:

• Colistin causes AKI in approximately 29.4% of patients, even with lower UTI and low MIC values 4

• Renal function must be monitored closely during colistin treatment if used 5

• Aminoglycosides, while effective as single-dose for cystitis, require careful dosing in renal impairment for complicated UTI 1

Combination therapy considerations:

• Polymyxin-based combinations should be guided by susceptibility testing 5

• Colistin monotherapy versus combination therapy shows no mortality difference (RR 1.03,95% CI 0.89-1.20), but combination does not reduce nephrotoxicity 6

• Carbapenem-containing combinations with fosfomycin or rifampin may be effective even against CRE in the urinary tract due to high urinary drug concentrations 7

Treatment Duration and Monitoring

• Complicated UTI duration: 7-14 days (14 days for men when prostatitis cannot be excluded) 2

• Always obtain susceptibility testing before finalizing therapy, as automated testing may be unreliable for multidrug-resistant organisms 1, 2

• Infectious disease consultation is highly recommended for all CRE infections 1, 2

• Consider prolonged infusion of β-lactams for pathogens with high MIC values 1

Pathogen-Specific Efficacy Data

For Klebsiella pneumoniae CRE-UTI specifically:

• Ceftazidime-avibactam showed 76.4% microbiological cure in the AVYCAZ arm versus 60.0% with carbapenems 3

• Aminoglycosides are superior to tigecycline for complicated UTI caused by CRE (moderate certainty evidence) 2

For E. coli CRE-UTI:

• Ceftazidime-avibactam demonstrated 76.3% microbiological cure versus 57.9% with best available therapy 3

• Single-dose aminoglycosides remain highly effective for simple cystitis 1, 2