BLING III RCT – Continuous vs. Intermittent Antibiotics

August 14, 2024

Written by Chris Thom

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This was a large RCT of critically ill adults with suspected infection who were randomized to receive either continuous infusions or intermittent dosages of intravenous antibiotics. 90-day mortality between groups was not statistically significant, while clinical cure rate was higher in the continuous infusion group.

Continuous antibiotic infusions may hold some benefit
This RCT randomized 7,202 adult ICU patients with suspicion for infection into receiving either continuous or intermittent infusions of beta-lactam antibiotics (piperacillin/tazobactam or meropenem). Characteristics of patients in each cohort were similar, with pulmonary pathology being the most common source of infection. APACHE II severity scores were similar between cohorts. The total 24-hour dose of antibiotic was left to the attending physician and the daily dose of study drugs was similar between arms.

The primary outcome of all-cause mortality at 90 days was not statistically different between the groups, with 864 of 3474 patients (24.9%) randomized to continuous infusion having expired and 939 of 3507 (26.8%) in the intermittent infusion arm expiring (OR 0.91, 95%CI 0.81 to 1.01). Clinical cure was defined as completion of the antibiotic treatment course by day 14 without further antibiotic therapy within 48 hours of cessation. Clinical cure was higher in the continuous infusion group (OR 1.26, 95%CI 1.15 to 1.38).

How will this change my practice?
While the primary outcome of mortality was not statistically different, the clinical cure rate was higher in the continuous infusion cohort. Interestingly, this trial had similar results to the MERCY¹ trial, which studied continuous versus intermittent meropenem in sepsis. There was also a small absolute reduction in mortality in the continuous infusion arm that did not meet statistical significance. The jury is out on whether continuous antibiotic infusions will improve mortality, but we are seeing some early evidence that it may be a strategy worth considering in ICU settings.

Source
Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial. JAMA. Published online June 12, 2024.

Work Cited

1. Monti G, Bradic N, Marzaroli M, et al. Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial. JAMA. 2023;330(2):141-151.