What are the recommended antibiotic regimens for complicated Urinary Tract Infections (UTIs)?

Recommended Antibiotic Regimens for Complicated UTIs

For complicated urinary tract infections (cUTIs), the recommended empiric antibiotic regimens include carbapenems, newer β-lactam/β-lactamase inhibitor combinations, or aminoglycosides, with treatment duration of 7-14 days depending on clinical response and source control. 1, 2

First-Line Parenteral Options

• Carbapenems: Consider in patients with early culture results indicating multidrug-resistant organisms 1

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

• Newer β-lactam/β-lactamase inhibitor combinations: Effective alternatives for resistant organisms 1, 2

  • Ceftolozane/tazobactam: 1.5 g three times daily 1
  • Ceftazidime/avibactam: 2.5 g three times daily 1, 2
  • Cefiderocol: 2 g three times daily 1

• Aminoglycosides: Recommended first-line therapy, especially with prior fluoroquinolone resistance 2

  • Gentamicin: 5 mg/kg once daily 1
  • Amikacin: 15 mg/kg once daily 1
  • Plazomicin: 15 mg/kg once daily 1

Oral Step-Down Options

• Fluoroquinolones: Only when local resistance is <10% 1, 3

  • Ciprofloxacin: 500-750 mg twice daily for 7 days 1, 3
  • Levofloxacin: 750 mg once daily for 5 days 1, 3, 4

• Trimethoprim-sulfamethoxazole: 160/800 mg twice daily for 14 days 1

• Oral cephalosporins:

  • Cefpodoxime: 200 mg twice daily for 10 days 1, 5
  • Ceftibuten: 400 mg once daily for 10 days 1
  • Cefuroxime: 500 mg twice daily for 10-14 days 5

Treatment Duration and Monitoring

• Treatment for 7-14 days is generally recommended, with 14 days for men when prostatitis cannot be excluded 1
• When the patient is hemodynamically stable and has been afebrile for at least 48 hours, a shorter treatment duration (7 days) may be considered 1
• Obtain urine culture before starting antibiotics to guide targeted therapy 2, 5
• Consider follow-up urine culture after completion of therapy to ensure resolution of infection 2, 5
• If symptoms persist after 72 hours of treatment, reevaluate diagnosis and consider imaging to rule out complications 2, 5

Special Considerations

• Multidrug-resistant organisms: The microbial spectrum in cUTIs is broader than for uncomplicated UTIs, with higher likelihood of resistance 1, 6
• Common pathogens include E. coli, Proteus spp., Klebsiella spp., Pseudomonas spp., Serratia spp., and Enterococcus spp. 1
• For ESBL-producing organisms, carbapenems, ceftazidime-avibactam, or ceftolozane-tazobactam are preferred 6, 7
• For carbapenem-resistant Enterobacteriaceae, consider ceftazidime-avibactam, colistin, aminoglycosides, or tigecycline 7
• Recent research shows cefepime/enmetazobactam has superior efficacy compared to piperacillin/tazobactam for cUTIs (79.1% vs 58.9% treatment success) 8

Factors Defining Complicated UTIs

• Obstruction at any site in the urinary tract, foreign body, incomplete voiding, vesicoureteral reflux 1
• Recent history of instrumentation, UTI in males, pregnancy, diabetes mellitus 1
• Immunosuppression, healthcare-associated infections 1
• ESBL-producing or multidrug-resistant organisms isolated 1

Management Approach

1. Obtain urine culture before initiating antibiotics 1, 2
2. Start empiric therapy based on local resistance patterns and patient risk factors 1, 7
3. Address underlying urological abnormalities or complicating factors 1
4. Adjust therapy based on culture results and clinical response 1, 2
5. Consider oral step-down therapy when the patient improves clinically 1, 3
6. Complete appropriate treatment duration based on clinical scenario 1, 2

Remember that appropriate management of the underlying urological abnormality or complicating factor is mandatory for successful treatment of complicated UTIs 1.