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

Treatment of Complicated Urinary Tract Infections

For complicated UTIs, initiate empiric parenteral therapy with a third-generation cephalosporin (ceftriaxone 1-2 g IV/IM once daily) or a combination of a second-generation cephalosporin plus an aminoglycoside, then narrow therapy based on culture results and continue for 7-14 days total. 1

Initial Empiric Therapy Selection

The choice of empiric antibiotic depends on illness severity and risk factors for resistant organisms:

For Moderate Severity Without MDR Risk Factors:

• Ceftriaxone 1-2 g IV/IM once daily (the higher 2 g dose is recommended for complicated infections) 1, 2
• Cefotaxime 2 g IV every 8 hours 1
• Cefepime 1-2 g IV every 12 hours 1
• Ciprofloxacin 400 mg IV every 12 hours (only if local resistance <10% and no recent fluoroquinolone exposure) 1, 3

For Severe Illness or Risk Factors for Resistance:

• Piperacillin-tazobactam 2.5-4.5 g IV every 8 hours 1
• Combination therapy: Second-generation cephalosporin PLUS aminoglycoside (gentamicin 5 mg/kg IV every 24 hours OR amikacin 15 mg/kg IV every 24 hours) 1

Critical caveat: Fluoroquinolones should NOT be used as first-line empiric therapy for serious complicated UTIs, especially when patients have risk factors for resistant organisms or recent fluoroquinolone exposure. 4

Treatment for Carbapenem-Resistant Enterobacteriaceae (CRE)

If CRE is suspected or confirmed, use newer beta-lactam/beta-lactamase inhibitor combinations:

• Ceftazidime-avibactam 2.5 g IV every 8 hours for 5-7 days 5, 1
• Meropenem-vaborbactam 4 g IV every 8 hours 5, 1
• Imipenem-cilastatin-relebactam 1.25 g IV every 6 hours 5, 1
• Plazomicin 15 mg/kg IV every 12 hours (particularly advantageous with lower mortality [24% vs 50%] and reduced acute kidney injury [16.7% vs 50%] compared to colistin-based regimens) 5, 1

Treatment Duration

• Standard complicated UTI: 7-14 days total 1, 2
• Men when prostatitis cannot be excluded: 14 days 1, 2
• CRE infections: 5-7 days (shorter duration acceptable with newer agents) 1
• Patients should be afebrile for at least 48 hours before considering switch to oral therapy 2

Transition to Oral Therapy

Once culture results are available and the patient is clinically stable (afebrile ≥48 hours):

• Switch to oral agent active against the identified pathogen 2
• Preferred oral options (if susceptible): Ciprofloxacin 500-750 mg twice daily, levofloxacin 750 mg daily, or cefpodoxime 200 mg twice daily 6
• Ensure the oral agent achieves adequate urinary concentrations 2

Essential Management Principles

Mandatory Culture and Susceptibility Testing:

• Obtain urine culture and sensitivity testing BEFORE initiating antibiotics (but do not delay treatment) 1, 6
• Blood cultures are appropriate in severe cases or when bacteremia is suspected 4
• Adjust empiric therapy based on culture results 1

Address Underlying Urological Abnormalities:

• Management of the anatomic or functional abnormality is obligatory for treatment success 1
• Consider imaging (ultrasound initially) if patient remains febrile after 72 hours or deteriorates 6
• Rule out obstruction or abscess formation, particularly in males 6

Common Pitfalls to Avoid

• Do NOT use nitrofurantoin or fosfomycin for complicated UTIs with systemic involvement - these agents achieve insufficient tissue concentrations for pyelonephritis or parenchymal infections 6, 4
• Do NOT rely on ceftriaxone alone for suspected ESBL-producing organisms - consider combination therapy or alternative agents 2
• Do NOT use single-dose aminoglycoside therapy for complicated UTIs - this is only appropriate for simple cystitis due to CRE 5
• Do NOT treat asymptomatic bacteriuria in non-pregnant patients 5

Risk Stratification for Resistant Organisms

Patients at higher risk for multidrug-resistant pathogens include those with: 1

• Recent healthcare exposure or hospitalization
• Recent antimicrobial use (especially fluoroquinolones or cephalosporins)
• Indwelling urinary catheters or recent instrumentation
• Known colonization with ESBL or CRE organisms
• Diabetes mellitus or immunosuppression

For these patients, empiric therapy should include broader-spectrum agents like piperacillin-tazobactam or carbapenems until susceptibilities are known. 4