What is the initial treatment approach for a patient with a multi-drug resistant (MDR) Klebsiella urinary tract infection (UTI)?

Initial Treatment Approach for MDR Klebsiella UTI

For patients with multi-drug resistant (MDR) Klebsiella urinary tract infection (UTI), ceftazidime-avibactam 2.5 g IV q8h is recommended as the initial treatment of choice when available. 1

First-line Treatment Options

• Obtain urine culture and antimicrobial susceptibility testing before initiating antibiotics to guide targeted therapy 2
• For complicated UTI due to MDR Klebsiella, the following options are recommended based on susceptibility:
  • Ceftazidime-avibactam 2.5 g IV q8h (first choice if available) 1
  • Meropenem-vaborbactam 4 g IV q8h 1
  • Imipenem-cilastatin-relebactam 1.25 g IV q6h 1
• For patients with simple cystitis due to MDR Klebsiella, single-dose aminoglycoside therapy can be considered if susceptible 1
• Plazomicin 15 mg/kg IV q12h is recommended for complicated UTI due to carbapenem-resistant Enterobacterales (CRE) 1, 3

Alternative Treatment Options

• For patients with non-severe infections due to CRE, use of an old antibiotic chosen from among the in vitro active agents should be considered on an individual basis 1
• For cystitis due to CRE, aminoglycosides are ideal agents as they achieve high urinary concentrations 1
• For patients with severe infections due to CRE carrying metallo-β-lactamases and/or resistant to all other antibiotics, cefiferocol is conditionally recommended 1
• For highly resistant pathogens with limited options:
  • Tigecycline may be considered for non-bacteremic UTIs if susceptible 4, 5
  • Fosfomycin can be used for susceptible strains 6, 7
  • Polymyxins (colistin) should be reserved for cases with no other options due to nephrotoxicity 4

Combination Therapy Considerations

• For patients with severe infections caused by CRE carrying metallo-β-lactamases, aztreonam and ceftazidime-avibactam combination therapy is suggested 1
• For patients with severe infections caused by CRE susceptible only to polymyxins, aminoglycosides, tigecycline, or fosfomycin, treatment with more than one drug active in vitro is suggested 1
• Carbapenem-based combination therapy should be avoided unless the meropenem MIC is ≤8 mg/L 1

Treatment Duration

• 7-14 days of therapy is recommended for complicated UTIs 2
• Treatment can be shortened to 7 days if the patient becomes hemodynamically stable and afebrile for at least 48 hours 2
• Longer duration (14 days) may be needed for men when prostatitis cannot be excluded 2

Monitoring and Follow-up

• Monitor renal function when using potentially nephrotoxic agents like aminoglycosides or polymyxins 2, 3
• Adjust therapy based on culture results and clinical response 2
• Evaluate for and address underlying factors such as urological abnormalities, urinary catheters, or obstruction 2

Common Pitfalls to Avoid

• Automated susceptibility testing systems may overestimate susceptibility for MDR organisms; consider requesting specific minimum inhibitory concentration (MIC) testing for critical antibiotics 4
• Fluoroquinolones should be avoided for empiric treatment if local resistance rates exceed 10% or if the patient has used them in the past 6 months 2
• Treating asymptomatic bacteriuria can increase resistance and should be avoided 2
• Inadequate treatment duration for complicated infections can lead to poor outcomes 2

Special Considerations

• For recurrent MDR Klebsiella UTIs that fail conventional antibiotic therapy, novel approaches like fecal microbiota transplantation may be considered in specialized settings 8
• Antimicrobial stewardship principles should be applied to preserve the effectiveness of newer agents 6, 7