What is the best treatment approach for a resistant Urinary Tract Infection (UTI)?

Treatment Approach for Resistant Urinary Tract Infections

For resistant UTIs, targeted therapy based on culture and susceptibility testing is essential, with newer agents like ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-cilastatin-relebactam recommended for complicated UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE). 1

Diagnostic Approach

• Obtain urinalysis and urine culture with sensitivity testing before initiating antibiotics to guide targeted therapy 1
• Document the specific resistant organism and its susceptibility pattern to select appropriate antimicrobial therapy 1
• Consider risk factors for resistant organisms including previous antibiotic use, healthcare exposure, and anatomical abnormalities 1

Treatment Algorithm for Resistant UTIs

For Uncomplicated Resistant Cystitis:

• First-line options (when susceptible):
  • Nitrofurantoin 100 mg PO every 6 hours for uncomplicated UTIs due to resistant organisms including VRE 1
  • Single-dose fosfomycin 3 g PO for uncomplicated UTIs due to resistant organisms including VRE 1
  • Single-dose aminoglycoside for simple cystitis due to CRE 1

For Complicated UTIs with Resistant Organisms:

• For CRE-associated complicated UTIs:
  • Ceftazidime-avibactam 2.5 g IV q8h (weak recommendation, very low quality evidence) 1
  • Meropenem-vaborbactam 4 g IV q8h (weak recommendation, low quality evidence) 1
  • Imipenem-cilastatin-relebactam 1.25 g IV q6h (weak recommendation, low quality evidence) 1
  • Plazomicin 15 mg/kg IV q12h (weak recommendation, very low quality evidence) 1

For Vancomycin-Resistant Enterococci (VRE) UTIs:

• Nitrofurantoin 100 mg PO every 6 hours (weak recommendation, very low quality evidence) 1
• Fosfomycin 3 g PO single dose (weak recommendation, very low quality evidence) 1
• High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg IV/PO every 8 hours (weak recommendation, very low quality evidence) 1

Duration of Therapy

• For uncomplicated resistant UTIs: 5-7 days of therapy is generally sufficient 1
• For complicated UTIs: 7-14 days of therapy is recommended 1
• For men with UTIs where prostatitis cannot be excluded: 14 days of therapy 1

Special Considerations

Carbapenem-Resistant Enterobacteriaceae (CRE)

• Newer β-lactam/β-lactamase inhibitor combinations are preferred over polymyxins when available 1
• Aminoglycosides maintain good activity against many CRE strains and achieve high urinary concentrations 1, 2
• For severe infections, combination therapy may be considered, though evidence is limited 1

Multidrug-Resistant Pseudomonas aeruginosa

• Consider ceftolozane-tazobactam 1.5-3 g IV q8h or ceftazidime-avibactam 2.5 g IV q8h 1
• Colistin monotherapy or combination therapy may be necessary for highly resistant strains 1

Common Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria except in pregnancy or before urologic procedures 1
• Avoid fluoroquinolones as empiric therapy for serious complicated UTIs due to increasing resistance rates 2, 3
• Do not continue broad-spectrum therapy when narrower options are available based on culture results 1
• Avoid unnecessary prolonged courses of antibiotics which increase risk of resistance 1
• Do not rely on previous culture results without obtaining new cultures in resistant UTI cases 1

Follow-up

• Consider follow-up urine culture after completion of therapy for resistant UTIs to confirm eradication 1
• For recurrent resistant UTIs, evaluate for anatomical abnormalities or foreign bodies that may serve as a nidus for infection 1
• Consider urologic consultation for patients with persistent resistant UTIs despite appropriate antimicrobial therapy 1

The management of resistant UTIs requires a careful balance between providing effective antimicrobial coverage while minimizing further development of resistance. Culture-guided therapy remains the cornerstone of treatment, with newer agents providing valuable options for multidrug-resistant organisms.