What are the antibiotics of choice for complicated urinary tract infections (UTIs)?

Antibiotics of Choice for Complicated Urinary Tract Infections

For complicated urinary tract infections (cUTIs), the first-line empirical parenteral therapy options include fluoroquinolones, aminoglycosides, extended-spectrum cephalosporins, or piperacillin-tazobactam, with selection based on local resistance patterns and patient-specific factors. 1

Definition and Characteristics of Complicated UTIs

Complicated UTIs occur when patients have:

• Host-related factors or anatomic/functional urinary tract abnormalities that make infection harder to eradicate
• Common complicating factors include:
  • Obstruction at any site in the urinary tract
  • Foreign body presence
  • Incomplete voiding
  • Vesicoureteral reflux
  • Recent instrumentation
  • Male gender
  • Pregnancy
  • Diabetes mellitus
  • Immunosuppression
  • Healthcare-associated infections
  • ESBL-producing or multidrug-resistant organisms 1

The microbial spectrum is broader than for uncomplicated UTIs, with higher likelihood of antimicrobial resistance. Common pathogens include E. coli, Proteus spp., Klebsiella spp., Pseudomonas spp., Serratia spp., and Enterococcus spp. 1

Empirical Parenteral Treatment Options

First-line options:

• Fluoroquinolones:

  • Ciprofloxacin 400 mg IV twice daily
  • Levofloxacin 750 mg IV once daily 1, 2

• Extended-spectrum cephalosporins:

  • Cefotaxime 2 g IV three times daily
  • Ceftriaxone 1-2 g IV once daily
  • Cefepime 1-2 g IV twice daily 1

• Penicillin combinations:

  • Piperacillin-tazobactam 2.5-4.5 g IV three times daily 1

• Aminoglycosides:

  • Gentamicin 5 mg/kg IV once daily
  • Amikacin 15 mg/kg IV once daily 1, 3

For multidrug-resistant organisms:

• Carbapenems:

  • Meropenem 1 g IV three times daily
  • Imipenem/cilastatin 0.5 g IV three times daily
  • Meropenem-vaborbactam 2 g IV three times daily 1

• Newer agents:

  • Ceftolozane-tazobactam 1.5 g IV three times daily
  • Ceftazidime-avibactam 2.5 g IV three times daily
  • Cefiderocol 2 g IV three times daily
  • Plazomicin 15 mg/kg IV once daily 1, 4

Treatment Duration and Approach

• Duration: Generally 7-14 days (14 days for men when prostatitis cannot be excluded)
• Shorter course: May be considered when the patient is hemodynamically stable and afebrile for at least 48 hours 1
• Critical steps:
  1. Obtain urine culture and susceptibility testing before starting antibiotics
  2. Start with empiric therapy based on local resistance patterns
  3. Tailor therapy once culture results are available
  4. Address underlying urological abnormality or complicating factor 1

Special Considerations

Fluoroquinolone Use

While fluoroquinolones have historically been effective for cUTIs, increasing resistance rates (>10% in many regions) have limited their empiric use. Levofloxacin is FDA-approved for both 5-day and 10-day treatment regimens for complicated UTIs, depending on the causative pathogen 2, 5.

Aminoglycoside Considerations

Gentamicin is particularly effective against Gram-negative pathogens including Pseudomonas, Proteus, E. coli, Klebsiella, Enterobacter, and Serratia species. However, it should be used with caution due to potential nephrotoxicity and ototoxicity, especially in patients with renal impairment 3.

Multidrug-Resistant Organisms

For ESBL-producing Enterobacterales, carbapenems remain the treatment of choice, though newer agents like ceftazidime-avibactam and ceftolozane-tazobactam have shown efficacy. For carbapenem-resistant organisms, options include ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol, and colistin as a last resort 4.

Common Pitfalls to Avoid

1. Failure to obtain cultures before starting antibiotics: Always collect specimens for bacterial culture to identify causative organisms and determine susceptibility 1, 3

2. Ignoring local resistance patterns: Treatment should be guided by local antimicrobial susceptibility data, as resistance rates vary significantly by region 6

3. Not addressing underlying abnormalities: Management of urological abnormalities or complicating factors is mandatory for successful treatment 1

4. Inappropriate fluoroquinolone use: Reserve for areas where resistance is <10% or when susceptibility is confirmed 1, 5

5. Inadequate treatment duration: Ensure appropriate duration based on clinical response and presence of complicating factors 1

6. Overlooking catheter-associated UTIs: These require special consideration as they are a leading cause of healthcare-associated bacteremia 1

By following these evidence-based recommendations and considering local resistance patterns, clinicians can optimize treatment outcomes for patients with complicated UTIs while minimizing the risk of treatment failure and antimicrobial resistance.