Can ceftriaxone be administered to a patient with Extended-Spectrum Beta-Lactamase (ESBL)-producing Escherichia coli (E. coli) urinary tract infection (UTI)?

Ceftriaxone Should Not Be Used for ESBL-Producing E. coli UTI

Ceftriaxone is not recommended for the treatment of urinary tract infections caused by ESBL-producing E. coli, as it demonstrates poor clinical and microbiological outcomes in this setting. 1

First-Line Treatment Options for ESBL-Producing E. coli UTI

• Carbapenems are the first-line treatment for ESBL-producing E. coli infections, with ertapenem being preferred due to its once-daily dosing and excellent efficacy 2
• Meropenem and imipenem-cilastatin are effective alternative carbapenem options with excellent activity against ESBL-producing organisms 2
• For uncomplicated lower UTIs specifically, fosfomycin shows high efficacy (>95% susceptibility) and can be used as an alternative to carbapenems 2
• Nitrofurantoin is effective against ESBL-producing E. coli (>90% susceptibility) but should only be used for lower UTIs, not for upper UTIs or other Enterobacteriaceae infections 2

Evidence Against Ceftriaxone for ESBL-Producing E. coli UTI

• A prospective study found both clinical (65% vs 93%) and microbiological (67.5% vs 100%) responses at 72 hours after ceftriaxone treatment were significantly poorer in ESBL-producing infections compared to non-ESBL infections (p<0.0002) 1
• Patients with ESBL-producing E. coli UTIs treated with empirical ceftriaxone experienced:
  • Longer time to defervescence (4.6±2.2 days vs 2.6±1.3 days, p<0.01) 3
  • Lower rates of microbiological resolution within 5 days (77% vs 100%, p=0.01) 3
  • Longer hospitalization duration (13.3±8.2 days vs 7.3±3.5 days, p<0.01) 3

Alternative Treatment Options

• Aminoglycosides may be effective for short-duration therapy in non-severe UTIs if susceptibility is confirmed 2
• Ceftazidime-avibactam shows excellent activity against ESBL-producing organisms and can be used as a carbapenem-sparing option for susceptible isolates 2
• Ceftolozane-tazobactam is effective against many ESBL-producing Enterobacteriaceae and may be valuable to preserve carbapenems 2

Important Clinical Considerations

• Local antimicrobial resistance patterns should guide empiric therapy decisions 2
• Despite the 2010 CLSI guidelines suggesting that cephalosporins could be reported as susceptible based on in vitro testing alone, clinical evidence demonstrates poor outcomes when ceftriaxone is used for ESBL-producing infections 4
• The consensus among experts is that cephalosporins, including ceftriaxone, should not be used for ESBL infections despite possible in vitro susceptibility 2
• For UTIs specifically, treatment duration should be 5-7 days for lower UTIs and 7-14 days for pyelonephritis 2

Monitoring and Follow-up

• Clinical response should be monitored within 48-72 hours of initiating therapy 2
• For bacteremic UTIs, follow-up blood cultures should be obtained to document clearance 2
• Consider repeat urine cultures 1-2 weeks after treatment completion 2

Common Pitfalls to Avoid

• Relying solely on in vitro susceptibility results for ceftriaxone can lead to treatment failure in ESBL-producing infections 5
• Delaying appropriate therapy (carbapenems) for ESBL-producing infections can result in longer hospitalization and delayed clinical improvement 3
• Using cephalosporins empirically in settings with high ESBL prevalence (>10-20%) is not recommended 4