BLISS
Trial question
What is the role of continuous infusion of β-lactam antibiotics in critically ill patients with severe sepsis not receiving RRT?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
31.0% female
69.0% male
N = 140
140 patients (44 female, 96 male).
Inclusion criteria: critically ill patients with severe sepsis who were not on RRT.
Key exclusion criteria: receipt of RRT; impaired hepatic function; receipt of palliative treatment; inadequate central venous catheter access; imminent death.
Interventions
N=70 continuous β-lactam antibiotics (continuous infusion of β-lactam antibiotics).
N=70 intermittent β-lactam antibiotics (intermittent bolus dosing of β-lactam antibiotics).
Primary outcome
Clinical cure at 14 days after antibiotic cessation
56%
34%
56.0 %
42.0 %
28.0 %
14.0 %
0.0 %
Continuous beta-lactam
antibiotics
Intermittent beta-lactam
antibiotics
Significant
increase ▲
NNT = 4
Significant increase in clinical cure at 14 days after antibiotic cessation (56% vs. 34%; AD 22%, 95% CI -0.4 to -0.1).
Secondary outcomes
Significant increase in the rate of plasma antibiotic concentrations measured at 100% of the dosing interval on day 3 (97% vs. 68%; AD 29%, 95% CI -0.4 to -0.1).
No significant difference in ventilator-free days (22 days vs. 14 days; AD 8 days, 95% CI -2 to 18).
No significant difference in ICU-free days (20 days vs. 17 days; AD 3 days, 95% CI -3 to 9).
Safety outcomes
No significant difference in 14-day survival and 30-day survival.
Significant difference in white cell count normalization days (3 days vs. 8 days).
Conclusion
In critically ill patients with severe sepsis who were not on RRT, continuous β-lactam antibiotics were superior to intermittent β-lactam antibiotics with respect to clinical cure at 14 days after antibiotic cessation.
Reference
Mohd H Abdul-Aziz, Helmi Sulaiman, Mohd-Basri Mat-Nor et al. Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis. Intensive Care Med. 2016 Oct;42(10):1535-1545.
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