No clear mortality benefit with continuous vs intermittent antibiotics in sepsis treatment

In the treatment of critically ill patients with sepsis, continuous infusion of β-lactam antibiotics does not appear to significantly reduce 90-day mortality compared with intermittent infusions, according to the results of an open-label BLING III trial.

The analysis included 7,031 adult patients (mean age 59 years, 35 percent female) from 104 intensive care units (ICUs) across Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the UK. These patients were randomly assigned to receive an equivalent 24-hour dose of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) via continuous (n=3,498) or intermittent (n=3,533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first.

All-cause mortality within 90 days after randomization was the primary outcome. Secondary outcomes included clinical cure up at day 14; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality.

Within 90 days, 864 patients in the continuous infusion group and 939 in the intermittent infusion group died (24.9 percent vs 26.8 percent), with the difference not reaching statistical significance (absolute difference, −1.9 percent, 95 percent confidence interval [CI], −4.9 to 1.1; odds ratio [OR], 0.91, 95 percent CI, 0.81–1.01; p=0.08).

Continuous infusion was associated with higher clinical cure rates compared with intermittent infusion (55.7 percent vs 50.0 percent; absolute difference, 5.7 percent, 95 percent CI, 2.4–9.1; OR, 1.26, 95 percent CI, 1.15–1.38). No significant differences were observed in other secondary outcomes.