‘Likely clinically important benefit’ with continuous beta-lactam antibiotic infusions

Key takeaways:

• When comparing continuous vs. intermittent infusions, the absolute difference in 90-day mortality was nonsignificant at –1.9%.
• For clinical cure by day 14, a significant absolute difference was observed.

More ICU patients with sepsis receiving a continuous vs. intermittent infusion of beta-lactam antibiotics achieved clinical cure by day 14, but 90-day mortality was similar, according to research published in JAMA.

“The BLING III trial provides important evidence to guide antibiotic management and improve outcomes for patients with sepsis,” Joel M. Dulhunty, MD, PhD, director of research and implementation at Royal Brisbane and Women’s Health, Metro North Health, said in a press release.

In the randomized, open-label, international BLING III trial, Dulhunty and colleagues assessed 7,031 ICU patients (mean age, 59 years; 35% women) with sepsis treated with a 24-hour piperacillin-tazobactam or meropenem (beta-lactam antibiotics) dose to determine the impact of continuous vs. intermittent infusions on 90-day all-cause mortality.

The continuous infusion group included 3,498 patients (mean age, 59.3 years; 34% women; 59% with pulmonary site of infection) and the intermittent infusion group included 3,533 patients (mean age, 59.6 years; 34.9% women; 60% with pulmonary site of infection).

Patients received their assigned infusion type for a length established by a clinician or until ICU discharge, according to researchers. Both groups had similar median treatment lengths (continuous, 5.8 days; intermittent, 5.7 days).

A slightly lower proportion of patients in the continuous vs. intermittent infusion group died by day 90 (24.9% vs. 26.8%), but the between group absolute difference was not statistically significant (–1.9%; 95% CI, –4.9% to 1.1%).

Despite this non-significance, Dulhunty and colleagues wrote, “the confidence interval around the effect estimate includes a clinically important benefit.”

A significant absolute difference between the two groups in this outcome was only seen following adjustment for prespecified covariates (–2.2%; 95% CI, –5.5% to 1.1%).

As an additional measure, researchers looked at clinical cure by day 14 between the two groups. Among those receiving the continuous beta-lactam antibiotic infusion, 55.7% achieved this outcome, and this was significantly greater than the 50% of patients who had clinical cure in the intermittent infusion group (absolute difference, 5.7%; 95% CI, 2.4%-9.1%).

In contrast, both groups had similar proportions of patients with new acquisition, colonization or infection with a multiresistant organism or Clostridioides difficile infection by day 14.

Researchers also looked for differences in ICU mortality and in-hospital mortality between the two infusion types. Similar to 90-day all-cause mortality, the two groups did not significantly differ from each other in either mortality classification.

Other comparable outcomes between the continuous infusion group and the intermittent infusion group included days alive and free of ICU stay, hospital stay, mechanical ventilation and kidney replacement therapy.

The population used to assess safety consisted of 6,950 patients who received a minimum of one dose of the beta-lactam antibiotic.

Compared with the intermittent infusion group, the continuous infusion group had four more adverse events (10 events vs. 6 events), one of which was considered serious (severe encephalopathy) and deemed “possibly related to meropenem treatment” by clinicians.

“While the difference in survival was not statistically significant, we conclude that these findings represent a likely clinically important benefit with the use of continuous infusions in adult patients treated for sepsis in the intensive care unit with piperacillin-tazobactam or meropenem,” Dulhunty said.

Reference:

• Continuous vs. intermittent B-lactam antibiotic infusions in critically ill patients with sepsis. https://www.eurekalert.org/news-releases/1047743. Published June 12, 2024. Accessed June 12, 2024.