Treatment of UTI with ESBL Klebsiella pneumoniae Bacteremia
For patients with urinary tract infection and bacteremia caused by ESBL-producing Klebsiella pneumoniae, ceftazidime/avibactam or meropenem/vaborbactam should be the first-line treatment options. 1
First-Line Treatment Options
- Ceftazidime/avibactam (2.5g IV every 8 hours) is strongly recommended as first-line therapy for infections caused by ESBL-producing Klebsiella pneumoniae with bacteremia 1
- Meropenem/vaborbactam (2g IV every 8 hours) is an equally effective first-line option with strong recommendation and moderate certainty of evidence 1
- Treatment duration should be 10-14 days for bacteremic UTIs, with consideration for longer duration based on clinical response 1, 2
Alternative Treatment Options
- Imipenem/relebactam may be considered as an alternative when first-line agents are unavailable (conditional recommendation, low certainty of evidence) 1
- Cefiderocol is another alternative option that can be considered when first-line agents cannot be used 1
- Carbapenems (ertapenem, meropenem, imipenem) remain effective against most ESBL-producing organisms but should be used judiciously to prevent development of carbapenem resistance 2, 3
Diagnostic Considerations
- Rapid testing strategies to identify specific resistance mechanisms are strongly recommended to guide appropriate antibiotic therapy early 1
- Susceptibility testing is essential as ESBL-producing K. pneumoniae may have variable resistance patterns 1, 4
- Blood cultures should be repeated to document clearance of bacteremia 2
Risk Factors and Considerations
- Previous antibiotic use (more than two cycles in the previous year) is significantly associated with ESBL-producing infections (OR 6.238) 4
- Recurrent UTIs (more than two cycles in the last 6 months or more than three cycles in the last year) are significantly associated with ESBL-producing infections (OR 7.356) 4
- Healthcare-associated infections and recent hospitalization increase the risk of ESBL-producing organisms 1, 5
Treatment Pitfalls to Avoid
- Avoid cephalosporins (except newer agents with β-lactamase inhibitors) as ESBL-producing organisms show high resistance to third-generation cephalosporins (70-100%) 4
- Do not use trimethoprim-sulfamethoxazole or fluoroquinolones empirically due to high resistance rates among ESBL-producing organisms 3, 4
- Traditional antibiotic regimens including colistin have shown poor efficacy and unfavorable toxicity profiles compared to newer agents 1
Evidence Strength
The recommendations for using ceftazidime/avibactam and meropenem/vaborbactam are based on observational studies with moderate certainty of evidence, as randomized controlled trials specifically for ESBL-producing K. pneumoniae infections are lacking 1. However, real-world experience has demonstrated significant benefits of these newer agents over traditional antibiotic regimens in terms of clinical efficacy and safety 1.
In a multicentre prospective registry study, patients with KPC-producing K. pneumoniae bloodstream infections treated with ceftazidime/avibactam had significantly lower 28-day mortality compared to those treated with other active agents (18.3% vs. 40.8%, p=0.005) 1.
For complicated UTIs specifically, AVYCAZ (ceftazidime/avibactam) is FDA-approved for the treatment of complicated urinary tract infections including pyelonephritis caused by susceptible gram-negative organisms including Klebsiella pneumoniae 6.