What is the recommended treatment for a patient with a multi-resistant urinary tract infection (UTI)?

Treatment for Multidrug-Resistant Urinary Tract Infections

For multidrug-resistant UTIs, obtain infectious disease consultation and urine culture with susceptibility testing immediately, then initiate empiric therapy with newer beta-lactam/beta-lactamase inhibitor combinations—specifically ceftazidime-avibactam 2.5 g IV every 8 hours, meropenem-vaborbactam 4 g IV every 8 hours, or imipenem-cilastatin-relebactam 1.25 g IV every 6 hours—reserving carbapenems and novel agents only for confirmed carbapenem-resistant Enterobacteriaceae (CRE) or when early culture results indicate multidrug-resistant organisms. 1, 2

Initial Management Approach

• Infectious disease consultation is mandatory for all infections caused by multidrug-resistant organisms, as this significantly impacts treatment selection and outcomes 1

• Obtain urine culture and antimicrobial susceptibility testing before initiating therapy, as microbiological documentation distinguishes true infection from colonization and guides targeted therapy 1, 2

• Assess for complicating factors that increase risk of resistant organisms: recent antibiotic exposure, healthcare-associated infection, nursing home residence, indwelling catheters, recent urological instrumentation, immunosuppression, or known colonization with ESBL/CRE organisms 2

Empiric Therapy Selection by Clinical Scenario

For Complicated UTI with Suspected Multidrug-Resistant Organisms

First-line parenteral options (choose based on local resistance patterns):

• Piperacillin-tazobactam 2.5-4.5 g IV every 8 hours 1, 2
• Cefepime 1-2 g IV every 12 hours 1, 2
• Ceftriaxone 1-2 g IV every 24 hours 1, 2
• Gentamicin 5 mg/kg IV every 24 hours or amikacin 15 mg/kg IV every 24 hours 1, 2

Critical caveat: Avoid empiric fluoroquinolones and trimethoprim-sulfamethoxazole due to resistance rates exceeding 40-50% in most communities with multidrug-resistant organisms 3, 4

For Confirmed Carbapenem-Resistant Enterobacteriaceae (CRE)

Preferred agents (select based on susceptibility results):

• Ceftazidime-avibactam 2.5 g IV every 8 hours for 5-7 days—this is the most extensively studied option with high-quality evidence 1, 2, 5

• Meropenem-vaborbactam 4 g IV every 8 hours for 5-7 days 1, 2

• Imipenem-cilastatin-relebactam 1.25 g IV every 6 hours for 5-7 days 1, 2

• Plazomicin 15 mg/kg IV every 12 hours—particularly advantageous with demonstrated lower mortality (24% vs 50%) and reduced acute kidney injury (16.7% vs 50%) compared to colistin-based regimens 2

For simple cystitis due to CRE: Single-dose aminoglycoside is acceptable 1

Important distinction: Do not use single-dose aminoglycoside therapy for complicated UTIs—this is only appropriate for simple cystitis 2

For Multidrug-Resistant Pseudomonas aeruginosa

• Ceftolozane-tazobactam 1.5 g IV every 8 hours is highly effective, including for febrile UTI in patients with neurogenic bladder 1, 6

• Ceftazidime-avibactam 2.5 g IV every 8 hours provides excellent coverage 1, 5

• Alternative options include piperacillin-tazobactam, cefepime, or carbapenems based on susceptibility 1, 5

• Aminoglycosides (amikacin preferred) remain active against many MDR Pseudomonas strains 5, 6

For Vancomycin-Resistant Enterococcus (VRE)

Uncomplicated UTI: Fosfomycin 3 g PO single dose achieves 88.1% cure rate 1, 2

Complicated UTI or bacteremia:

• Linezolid 600 mg IV or PO every 12 hours 1
• High-dose daptomycin 8-12 mg/kg IV daily, with or without beta-lactam combination therapy for bacteremia 1

Treatment Duration

• Complicated UTI: 7-14 days is standard 1, 2

• CRE infections: 5-7 days is sufficient for most cases 1, 2

• Male patients: Minimum 14 days, as prostatitis cannot be excluded initially 2

• Patients hemodynamically stable and afebrile for ≥48 hours: Consider 7-10 days 2

Critical Pitfalls to Avoid

• Never treat asymptomatic bacteriuria in non-pregnant patients or those with catheters—this increases resistance without clinical benefit 2

• Avoid tigecycline monotherapy for pneumonia due to carbapenem-resistant Acinetobacter baumannii, though it may be used for intra-abdominal CRE infections 1

• Do not use empiric carbapenems for uncomplicated pyelonephritis—reserve these agents strictly for confirmed multidrug-resistant organisms 1, 7

• Address underlying urological abnormalities—antimicrobial therapy alone is insufficient without correcting anatomical or functional problems 1, 2

• Remove or replace indwelling catheters when possible before or during treatment of catheter-associated UTI 2

Adjunctive Measures

• Consider prolonged infusion of beta-lactams for pathogens with high minimum inhibitory concentrations to optimize pharmacodynamics 1

• For catheter-associated UTI, only treat if symptomatic—catheter removal or replacement is essential 2

• Combination antimicrobial therapy should be based on susceptibility testing results, particularly for bloodstream infections 1