Clinical question: Does continuous infusion of β-lactam antibiotics reduce 90-day mortality compared with intermittent infusion in critically ill patients with sepsis?
Background: Sepsis, a life-threatening response to infection, often requires treatment with β-lactam antibiotics such as piperacillin-tazobactam or meropenem. The administration method—continuous versus intermittent infusion—may impact outcomes, but it is uncertain if continuous infusion reduces mortality risk in these patients. This study aimed to assess whether continuous infusion improves survival in critically ill adults with sepsis over 90 days compared to intermittent infusion.
Study design: An international, open-label, randomized, clinical trial
Setting: 104 intensive care units (ICUs) across Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom
Synopsis: In this trial, 7,202 critically ill adults with sepsis who were treated with piperacillin-tazobactam or meropenem were randomized to receive either continuous (n=3,498) or intermittent (n=3,533) infusions of a β-lactam antibiotic for the duration of their ICU stay or treatment course. The primary outcome measured was all-cause mortality at 90 days post-randomization. Secondary outcomes included clinical cure by 14 days, acquisition of multi-resistant organisms or Clostridium difficile infection, ICU mortality, and in-hospital mortality.
Results indicated that at 90 days, mortality was 24.9% in the continuous infusion group and 26.8% in the intermittent group, showing an absolute difference of -1.9% (95% CI, -4.9% to 1.1%) but without statistical significance (P=.08). However, clinical cure was higher in the continuous infusion group (55.7%) compared to the intermittent group (50.0%), with an absolute difference of 5.7% (95% CI, 2.4% to 9.1%). Other secondary outcomes were similar and not statistically significant between groups.
Bottom line: Continuous infusion of β-lactam antibiotics did not significantly reduce 90-day mortality in critically ill sepsis patients compared to intermittent infusion. Nonetheless, continuous infusion demonstrated a higher rate of clinical cure, suggesting a possible therapeutic benefit that warrants further research.
Citation: Dulhunty JM, et al. Continuous vs intermittent β-lactam antibiotic infusions in critically ill patients with sepsis: the BLING III randomized clinical trial. JAMA. 2024;332(8):629-637. doi:10.1001/jama.2024.9779.
Dr. Kuruvilla is an assistant clinical professor of medicine in the division of hospital medicine at UC San Diego Health at the University of California in San Diego.