What is the recommended treatment for a complicated urinary tract infection?

Treatment of Complicated Urinary Tract Infections

For complicated UTIs, initiate empiric parenteral therapy with carbapenems (meropenem 1g three times daily or imipenem/cilastatin 0.5g three times daily), newer β-lactam/β-lactamase inhibitor combinations (ceftolozane/tazobactam 1.5g three times daily or ceftazidime/avibactam 2.5g three times daily), or aminoglycosides (gentamicin 5mg/kg once daily or amikacin 15mg/kg once daily), then transition to oral therapy based on culture results for 7-14 days total duration. 1, 2

Initial Assessment and Culture Requirements

Before initiating antibiotics, obtain urine culture and susceptibility testing in all patients with complicated UTIs, as the microbial spectrum is broader and antimicrobial resistance is more likely than in uncomplicated infections. 1, 2 The most common pathogens include E. coli, Proteus spp., Klebsiella spp., Pseudomonas spp., Serratia spp., and Enterococcus spp. 1

Defining Complicated UTIs

Complicated UTIs occur when host-related factors or anatomic/functional abnormalities make infection harder to eradicate. 1 Key complicating factors include:

• Obstruction at any urinary tract site, foreign body, incomplete voiding, vesicoureteral reflux 1
• Recent instrumentation, indwelling catheters 1
• Male sex, pregnancy, diabetes mellitus, immunosuppression 1
• Healthcare-associated infections 1
• ESBL-producing or multidrug-resistant organisms 1

Empiric Parenteral Therapy Options

First-Line Broad-Spectrum Agents

For severe complicated UTIs or when multidrug-resistant organisms are suspected:

• Carbapenems: Meropenem 1g three times daily, imipenem/cilastatin 0.5g three times daily, or meropenem-vaborbactam 2g three times daily 1, 2
• Newer β-lactam combinations: Ceftolozane/tazobactam 1.5g three times daily, ceftazidime/avibactam 2.5g three times daily, or cefiderocol 2g three times daily 1, 2
• Aminoglycosides: Gentamicin 5mg/kg once daily, amikacin 15mg/kg once daily, or plazomicin 15mg/kg once daily 1, 2

Alternative Parenteral Options

For less severe presentations or when fluoroquinolone resistance is <10%:

• Ciprofloxacin 400mg twice daily or levofloxacin 750mg once daily 1
• Ceftriaxone 1-2g once daily or cefepime 1-2g twice daily 1
• Piperacillin/tazobactam 2.5-4.5g three times daily 1

Critical caveat: Fluoroquinolones should not be used empirically for serious complicated UTIs when patients have risk factors for resistant organisms, including recent fluoroquinolone exposure. 3

Oral Step-Down Therapy

Once the patient is hemodynamically stable and afebrile for at least 48 hours, transition to oral therapy based on culture results: 1, 2

• Fluoroquinolones (if susceptible and local resistance <10%): Ciprofloxacin 500-750mg twice daily for 7 days or levofloxacin 750mg once daily for 5 days 1, 4
• Trimethoprim-sulfamethoxazole: 160/800mg twice daily for 14 days (if susceptible) 1
• Oral cephalosporins: Cefpodoxime 200mg twice daily for 10 days or ceftibuten 400mg once daily for 10 days 1, 2

Treatment Duration

Standard duration is 7-14 days, with specific considerations: 1, 2

• 7 days: For patients with prompt symptom resolution, hemodynamic stability, and afebrile for ≥48 hours 1, 2
• 14 days: For men when prostatitis cannot be excluded 1, 2
• Extended duration: May be necessary when underlying urological abnormalities cannot be promptly corrected 1

Special Considerations for Multidrug-Resistant Organisms

Carbapenem-Resistant Enterobacteriaceae (CRE)

For confirmed or suspected CRE infections:

• Ceftazidime/avibactam: 2.5g IV every 8 hours 1, 2
• Meropenem/vaborbactam: 2g (4g total dose) IV every 8 hours 1, 2
• Imipenem/cilastatin/relebactam: 1.25g IV every 6 hours 5
• Plazomicin: 15mg/kg IV every 12 hours (specifically for CRE-related complicated UTIs, with evidence showing lower mortality [24% vs 50%] and reduced acute kidney injury [16.7% vs 50%] compared to colistin-based regimens) 2, 5

Pseudomonas aeruginosa (Multidrug-Resistant)

Treatment options include ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, or aminoglycosides based on susceptibility testing. 6

Management of Underlying Abnormalities

Addressing the underlying urological abnormality is mandatory for successful treatment. 1, 2 This includes:

• Removing or replacing indwelling catheters that have been in place ≥2 weeks at infection onset 2
• Relieving urinary obstruction 1
• Managing incomplete bladder emptying 1

Common pitfall: Failing to address the underlying complicating factor leads to treatment failure and recurrence, regardless of appropriate antibiotic selection. 1

Monitoring and Adjustment

• Reassess at 72 hours if no clinical improvement with defervescence 2
• Adjust therapy based on culture and susceptibility results 1, 2
• Consider extended treatment and urologic evaluation for delayed response 2
• Obtain follow-up urine culture after treatment completion to ensure infection resolution 2