Can the Ceftriaxone Breakpoints Be Increased Without Compromising Patient Outcomes?

Area of Science:

• Infectious Diseases
• Clinical Microbiology
• Antimicrobial Stewardship

Background:

• Current ceftriaxone breakpoints for Enterobacteriaceae are 1 mcg/mL, based on limited clinical data.
• A 2010 recommendation lowered breakpoints despite insufficient evidence.

Purpose of the Study:

• To compare clinical outcomes of ceftriaxone versus extended-spectrum agents for Enterobacteriaceae bloodstream infections.
• To evaluate if increasing the ceftriaxone susceptibility breakpoint to 2 mcg/mL impacts patient outcomes.

Main Methods:

• Retrospective cohort study of adults with Enterobacteriaceae bacteremia and ceftriaxone MICs of 2 mcg/mL.
• Patients treated with ceftriaxone or extended-spectrum β-lactams were matched using propensity scores (1:2 ratio).
• Outcomes assessed included recurrent bacteremia and 30-day mortality.

Main Results:

• No significant differences in recurrent bacteremia (OR, 1.16; 95% CI, 0.49-2.73) or mortality (OR, 1.27; 95% CI, 0.56-2.91) were observed between groups.
• Matched groups (108 ceftriaxone, 216 extended-spectrum agents) were well-balanced on clinical characteristics.
• Extended-spectrum β-lactamase (ESBL)-producing isolates were rare (1.6%).

Conclusions:

• Ceftriaxone demonstrated similar efficacy to extended-spectrum agents for Enterobacteriaceae infections with ceftriaxone MICs of 2 mcg/mL.
• Consideration should be given to increasing the ceftriaxone susceptibility breakpoint to 2 mcg/mL.
• An increased breakpoint may reduce the reliance on broad-spectrum antibiotics.