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

Treatment of Complicated Urinary Tract Infections

For complicated UTIs, obtain urine culture before starting antibiotics, then initiate empiric IV therapy with ceftriaxone 1-2g daily, piperacillin/tazobactam 2.5-4.5g three times daily, or an aminoglycoside, and treat for 7-14 days depending on clinical response, with 14 days required for men when prostatitis cannot be excluded. 1

Initial Diagnostic Approach

Always obtain urine culture and susceptibility testing before initiating antimicrobial therapy due to the wide spectrum of potential organisms and increased likelihood of antimicrobial resistance in complicated UTIs 1. This is non-negotiable and distinguishes complicated from uncomplicated UTI management.

Common pathogens include:

• E. coli, Proteus spp., Klebsiella spp., Pseudomonas spp., Serratia spp., and Enterococcus spp. 1
• Multidrug-resistant organisms are more common in complicated UTIs 2

Empiric Antibiotic Selection

For Hospitalized or Severely Ill Patients (IV Therapy)

First-line parenteral options 1:

• Ceftriaxone 1-2g once daily
• Piperacillin/tazobactam 2.5-4.5g three times daily
• Aminoglycoside (gentamicin 5 mg/kg once daily, amikacin 15 mg/kg once daily) with or without ampicillin 1, 2

For multidrug-resistant organisms (reserve for culture-confirmed resistance) 2:

• Carbapenems: imipenem/cilastatin 0.5g three times daily, meropenem 1g three times daily, or meropenem-vaborbactam 2g three times daily
• Newer β-lactam/β-lactamase inhibitor combinations: ceftolozane/tazobactam 1.5g three times daily, ceftazidime/avibactam 2.5g three times daily, or cefiderocol 2g three times daily
• Plazomicin 15 mg/kg once daily specifically for carbapenem-resistant Enterobacteriaceae 2

Critical pitfall: Avoid carbapenems and novel broad-spectrum antimicrobials unless culture results indicate multidrug-resistant organisms 1. Overuse drives resistance.

Oral Step-Down Therapy

Switch to oral therapy when the patient is hemodynamically stable and has been afebrile for at least 48 hours 1, 2.

Oral options 1, 2:

• Levofloxacin 500mg once daily (or 750mg once daily for 5-day regimen in mild cases) 1, 3
• Trimethoprim-sulfamethoxazole 160/800mg twice daily
• Nitrofurantoin (for first-line treatment when susceptible)
• Oral cephalosporins: cefpodoxime 200mg twice daily, ceftibuten 400mg once daily, or cefuroxime 500mg twice daily 2

Fluoroquinolone restrictions (critical to avoid resistance): Only use fluoroquinolones when local resistance rates are <10% AND the patient has no history of fluoroquinolone use in the past 6 months 1. Never use moxifloxacin for UTI treatment due to uncertainty regarding effective urinary concentrations 1.

Treatment Duration

Standard duration is 14 days for complicated UTIs 1. However, duration should be tailored based on specific clinical scenarios:

Shorter Durations (7 days or less):

• 7 days: For catheter-associated UTIs with prompt symptom resolution 1
• 5 days: Levofloxacin 750mg once daily may be considered in patients with mild complicated UTI who are not severely ill 1, 3
• 3 days: May be considered for women aged ≤65 years who develop catheter-associated UTI without upper urinary tract symptoms after an indwelling catheter has been removed 1

Standard Duration (14 days):

• 14 days: For patients with delayed clinical response 1
• 14 days: For male patients when prostatitis cannot be excluded 1, 2
• 10-14 days: For catheter-associated UTIs with delayed response 1

Important caveat: Recent evidence suggests short-duration therapy (5-7 days) results in similar clinical success as long-duration therapy (10-14 days), even in patients with bacteremia, though one subgroup analysis showed 7-day ciprofloxacin was inferior to 14-day therapy in men 1. This underscores the importance of the 14-day duration for males.

Special Considerations

Catheter-Associated UTIs

• Replace the catheter if it has been in place for ≥2 weeks at onset of catheter-associated UTI and is still indicated, to hasten resolution of symptoms 1
• Remove the urinary catheter as soon as clinically appropriate 1

Male UTIs

• Always classify male UTIs as complicated due to broader microbial spectrum and higher likelihood of antimicrobial resistance 1
• Treat for 14 days when prostatitis cannot be excluded 1, 2

Multidrug-Resistant Organisms

• Plazomicin is specifically recommended for complicated UTI caused by carbapenem-resistant Enterobacteriaceae at 15 mg/kg IV every 12 hours, with demonstrated lower mortality (24% vs. 50%) and lower acute kidney injury (16.7% vs. 50%) compared to colistin-based regimens 2

Monitoring and Adjustment

Reassess after 48-72 hours of empiric therapy to evaluate clinical response 1:

• Adjust therapy based on culture and susceptibility results
• If no clinical improvement with defervescence by 72 hours, extend treatment and perform urologic evaluation 1

Complete the full course even after symptom resolution to prevent relapse 1.

Critical Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria in non-pregnant, non-catheterized patients—this leads to inappropriate antimicrobial use and resistance 1
• Do not use shorter treatment courses (<14 days) in males unless prostatitis has been definitively excluded 1
• Avoid fluoroquinolones as empiric therapy if local resistance rates exceed 10% or if the patient has used fluoroquinolones in the past 6 months 1
• Do not fail to replace long-term catheters (≥2 weeks) at treatment initiation, as this reduces treatment efficacy 1