What is the recommended work‑up and antibiotic therapy for a complicated urinary tract infection in an adult?

Complicated Urinary Tract Infection: Work-Up and Antibiotic Therapy

For adults with complicated UTI, obtain a urine culture before starting antibiotics, initiate empiric parenteral therapy with ceftriaxone 1–2 g IV once daily or a carbapenem if multidrug resistance is suspected, then transition to oral fluoroquinolones or trimethoprim-sulfamethoxazole based on susceptibility results for a total duration of 7–14 days. 1

Defining a Complicated UTI

A UTI is classified as complicated when any of the following factors are present: 1

• Urinary tract obstruction
• Indwelling catheter or other foreign body
• Incomplete bladder voiding or vesicoureteral reflux
• Recent urological instrumentation
• Male sex
• Pregnancy
• Diabetes mellitus or immunosuppression
• Healthcare-associated infection
• Isolation of ESBL-producing or multidrug-resistant organisms

All UTIs in men are considered complicated because prostatitis cannot be reliably excluded at initial presentation. 2

Pre-Treatment Work-Up

Mandatory Diagnostic Steps

Obtain urine culture with susceptibility testing before initiating antibiotics in every case of complicated UTI. 1 This is non-negotiable because complicated UTIs involve a broader microbial spectrum (E. coli, Proteus, Klebsiella, Pseudomonas, Serratia, Enterococcus) and exhibit markedly higher antimicrobial resistance rates compared to uncomplicated infections. 1

Assess for underlying urological abnormalities requiring source control (obstruction, stones, incomplete voiding, foreign bodies), because antimicrobial therapy alone is insufficient without addressing these structural problems. 1

Replace indwelling catheters that have been in place ≥2 weeks at the onset of treatment and obtain culture from the newly placed catheter; this accelerates symptom resolution and reduces recurrence risk. 1

Additional Evaluation

• Blood cultures are appropriate when fever, rigors, hypotension, or sepsis is present; bacteremia occurs in approximately 6% of UTIs in older patients. 2
• Imaging (CT or ultrasound) should be obtained if fever persists beyond 72 hours despite appropriate therapy, to rule out obstruction or abscess. 1, 3

Empiric Parenteral Therapy

First-Line Options for Moderate-Severe Disease

Ceftriaxone 1–2 g IV/IM once daily is the preferred initial empiric agent for most complicated UTIs requiring parenteral therapy, providing broad-spectrum coverage while awaiting culture results. 1 The 2 g dose is preferred for severe infections or high-resistance settings. 1

Cefepime 1–2 g IV every 12 hours (use 2 g for severe infections) is an appropriate alternative, particularly when Pseudomonas coverage is needed. 1

Piperacillin-tazobactam 3.375–4.5 g IV every 6 hours is suitable when multidrug-resistant organisms or Pseudomonas are suspected. 1 For nosocomial UTI with suspected Pseudomonas, combine with an aminoglycoside. 1

When to Use Carbapenems

Reserve carbapenems for patients with early culture results indicating multidrug-resistant organisms or when ESBL-producing bacteria are suspected. 1 Options include:

• Meropenem 1 g IV three times daily 1
• Imipenem-cilastatin 0.5 g IV three times daily 1
• Ertapenem 1 g IV once daily (suitable for ESBL but lacks Pseudomonas coverage) 1

Do not use carbapenems empirically for routine complicated UTIs when narrower-spectrum agents are appropriate; this practice preserves carbapenems for the most resistant pathogens. 1

Newer β-Lactam/β-Lactamase Inhibitor Combinations

For carbapenem-resistant Enterobacterales (CRE) or multidrug-resistant Pseudomonas: 1

• Ceftazidime-avibactam 2.5 g IV three times daily 1
• Ceftolozane-tazobactam 1.5 g IV three times daily 1
• Meropenem-vaborbactam 2 g IV three times daily 1
• Cefiderocol 2 g IV three times daily 1

Aminoglycosides

Gentamicin 5 mg/kg IV once daily or amikacin 15 mg/kg IV once daily are first-line options, especially with prior fluoroquinolone resistance. 1 However, avoid aminoglycosides until creatinine clearance is calculated because they are nephrotoxic and require precise weight-based dosing adjusted for renal function. 1

Oral Step-Down Therapy

Transition to oral therapy once the patient is clinically stable (afebrile ≥48 hours, hemodynamically stable, able to tolerate oral intake). 1

Preferred Oral Agents (Susceptibility-Guided)

Fluoroquinolones are the preferred oral step-down agents when the isolate is susceptible and local resistance is <10%: 1

• Levofloxacin 750 mg once daily for 5–7 days 1
• Ciprofloxacin 500–750 mg twice daily for 7 days 1

Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days is an alternative when the organism is susceptible and fluoroquinolones are contraindicated. 1

Less Effective Alternatives

Oral cephalosporins (cefpodoxime 200 mg twice daily for 10 days, ceftibuten 400 mg once daily for 10 days, cefuroxime 500 mg twice daily for 10–14 days) can be used but are associated with 15–30% higher failure rates compared to fluoroquinolones. 1

Amoxicillin-clavulanate 875/125 mg twice daily may be used when the pathogen is susceptible, but worldwide resistance to amoxicillin alone is very high. 1

Treatment Duration Algorithm

7 days total is sufficient when: 1

• Symptoms resolve promptly
• Patient is afebrile ≥48 hours
• Hemodynamically stable
• No evidence of upper-tract involvement or urological abnormalities

14 days total is required when: 1

• Delayed clinical response (fever persisting >72 hours)
• Male patient (prostatitis cannot be excluded) 1, 2
• Underlying urological abnormalities present
• Immunocompromised host

For men specifically, recent evidence shows 7-day ciprofloxacin was inferior to 14-day therapy (86% vs. 98% cure rate), supporting the 14-day recommendation. 2

Critical Pitfalls to Avoid

Do not use fluoroquinolones empirically when: 1

• Local resistance exceeds 10%
• Patient has recent fluoroquinolone exposure (within 6 months)
• Patient is from a urology department (higher resistance rates)

Do not use nitrofurantoin or fosfomycin for complicated UTIs because they have limited tissue penetration and lack efficacy data for upper-tract infections. 1

Do not treat asymptomatic bacteriuria in catheterized patients; this leads to inappropriate antimicrobial use and promotes resistance without clinical benefit. 1

Do not use moxifloxacin for UTI treatment due to uncertainty regarding effective urinary concentrations. 1

Do not omit catheter replacement (≥2 weeks old) at treatment initiation; failure to replace reduces treatment efficacy and increases recurrence risk. 1

Monitoring and Follow-Up

Reassess clinical response at 48–72 hours. 1 If the patient remains febrile or symptomatic:

• Obtain repeat urine culture
• Consider imaging to rule out obstruction or abscess 1
• Adjust therapy based on culture results 1
• Evaluate for structural urological abnormalities requiring intervention 1

Obtain follow-up urine culture after completion of therapy to ensure resolution of infection in complicated cases. 1