What is the recommended treatment for complicated urinary tract infections (UTIs)?

Treatment of Complicated Urinary Tract Infections

For complicated urinary tract infections (cUTIs), the recommended empirical treatment is a combination of amoxicillin plus an aminoglycoside, a second-generation cephalosporin plus an aminoglycoside, or an intravenous third-generation cephalosporin. 1, 2

Definition and Associated Factors

Complicated UTIs occur when host-related factors or anatomic/functional abnormalities make infection eradication more challenging compared to uncomplicated infections. These factors include:

• Obstruction at any site in the urinary tract 1
• Presence of foreign bodies 1
• Incomplete voiding 1
• Vesicoureteral reflux 1
• Recent history of instrumentation 1
• UTI in males 1
• Pregnancy 1
• Diabetes mellitus 1
• Immunosuppression 1
• Healthcare-associated infections 1
• ESBL-producing or multidrug-resistant organisms 1

Microbial Spectrum

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

Empirical Treatment Options

First-line Parenteral Therapy

• Amoxicillin plus an aminoglycoside 1, 2
• Second-generation cephalosporin plus an aminoglycoside 1, 2
• Intravenous third-generation cephalosporin 1, 2

Specific Parenteral Options

• Ciprofloxacin 400 mg every 12 hours 1, 2
• Cefotaxime 2 g every 8 hours 1, 2
• Ceftriaxone 1-2 g daily 1, 2
• Cefepime 1-2 g every 12 hours 1, 2
• Piperacillin/tazobactam 2.5-4.5 g every 8 hours 1, 2
• Gentamicin 5 mg/kg daily 1, 2, 3
• Amikacin 15 mg/kg daily 1, 2

Oral Treatment Options

• Ciprofloxacin should only be used if local resistance rates are <10% and when:
  • The entire treatment is given orally 1
  • The patient does not require hospitalization 1
  • The patient has anaphylaxis to β-lactam antimicrobials 1
• Levofloxacin 750 mg daily (for 5-10 days depending on severity) 1, 4

Treatment for Resistant Pathogens

For infections caused by multidrug-resistant organisms:

• For ESBL-producing Enterobacteriaceae: carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, or aminoglycosides 2, 5, 6
• For carbapenem-resistant Enterobacteriaceae: ceftazidime-avibactam, meropenem/vaborbactam, colistin, or cefiderocol 2, 5
• For multidrug-resistant Pseudomonas: ceftolozane-tazobactam, ceftazidime-avibactam, or colistin 5, 6

Duration of Treatment

• Treatment duration is typically 7-14 days 1, 2
• For men when prostatitis cannot be excluded, 14 days of treatment is recommended 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 if there are relative contraindications to the antibiotic being used 1

Comprehensive Management Approach

• Appropriate management of the underlying urological abnormality or complicating factor is mandatory 1
• Urine culture and susceptibility testing should always be performed 1
• Initial empiric therapy should be tailored based on culture results 1

Important Considerations and Pitfalls

• Fluoroquinolones should not be used for empirical treatment in patients from urology departments or when patients have used fluoroquinolones in the last 6 months due to resistance concerns 1, 6
• Monitor for nephrotoxicity and ototoxicity when using aminoglycosides, especially in patients with renal impairment or prolonged therapy 3
• Consider local resistance patterns when selecting empiric therapy 5, 7
• For catheter-associated UTIs, catheter removal or exchange should be considered when possible 1

By following these evidence-based recommendations, clinicians can effectively manage complicated UTIs while minimizing the risk of treatment failure and antimicrobial resistance.