BLING III
Trial question
Is continuous β-lactam antibiotic infusion superior to intermittent β-lactam antibiotic infusion in critically ill patients with sepsis?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
34.0% female
66.0% male
N = 7031
7031 patients (2423 female, 4608 male).
Inclusion criteria: critically ill adults treated with piperacillin/tazobactam or meropenem for sepsis.
Key exclusion criteria: age < 18 years; receipt of piperacillin/tazobactam or meropenem for > 24 hours during current infection episode; pregnancy; allergy to piperacillin/tazobactam, meropenem, or penicillin; receipt of RRT.
Interventions
N=3498 continuous infusion (piperacillin/tazobactam or meropenem over 24 hours infusion).
N=3533 intermittent infusion (piperacillin/tazobactam or meropenem over a 30 minute infusion).
Primary outcome
Rate of death within 90 days
24.9%
26.8%
26.8 %
20.1 %
13.4 %
6.7 %
0.0 %
Continuous
infusion
Intermittent
infusion
No significant
difference ↔
No significant difference in the rate of death within 90 days (24.9% vs. 26.8%; OR 0.91, 95% CI 0.81 to 1.01).
Secondary outcomes
Significant increase in clinical cure at day 14 (55.7% vs. 50%; OR 1.26, 95% CI 1.15 to 1.38).
No significant difference in new acquisition, colonization, or infection with a multidrug-resistant organism or C. difficile infection at day 14 (7.2% vs. 7.5%; OR 0.96, 96% CI 0.8 to 1.15).
No significant difference in death in the ICU (17.1% vs. 18.4%; OR 0.92, 95% CI 0.81 to 1.04).
Safety outcomes
No significant difference in adverse events.
Conclusion
In critically ill adults treated with piperacillin/tazobactam or meropenem for sepsis, continuous infusion was not superior to intermittent infusion with respect to the rate of death within 90 days.
Reference
Joel M Dulhunty, Stephen J Brett, Jan J De Waele et al. Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial. JAMA. 2024 Aug 27;332(8):629-637.
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