OBJECTIVES: To compare the clinical and bacteriological outcome of critically ill patients with sepsis treated byceftriaxone administered as a once-a-day intermittent bolus dose or by 24 h continuous infusion. PATIENTS AND METHODS: We conducted an open-label, randomized controlled pilot study in 57 patients clinically diagnosed with sepsis (suspected/proven infection and systemic inflammatory response syndrome) in a tertiary level intensive care unit. Patients were randomized to receive 2 g of ceftriaxone administered by once-daily intermittent bolus dosing or by 24 h continuous infusion. Clinical and bacteriological outcomes were assessed by blinded clinicians. RESULTS:Fifty-seven patients were enrolled in the study, 50 of whom fulfilled the a priori definition of treatment for 4 or more days. The infusion (n = 29) and bolus groups (n = 28) were similar in terms of demographics, although the median age of those receiving the infusion was younger. Intention-to-treat analysis found no statistically significant differences in the primary outcomes for clinical response (P = 0.17), clinical cure [infusion n = 13/29 versus bolus n = 5/28; adjusted odds ratio (AOR) = 3.74; 95% confidence interval (95% CI) = 1.11-12.57; P = 0.06], bacteriological response (P = 0.41) and bacteriological cure (infusion n = 18/29 versus bolus 14/28; AOR = 1.64; 95% CI = 0.57-4.70; P = 0.52). However, logistic regression in patients that complied with the a priori definitions who received ceftriaxone by continuous infusion (AOR = 22.8; 95% CI = 2.24-232.3; P = 0.008) or patients with a low Acute Physiology and Chronic Health Evaluation (APACHE) II score (AOR = 0.70; 95% CI = 0.54-0.91; P = 0.008) were associated with an improved clinical outcome when age and Sepsis Organ Failure Assessment (SOFA) score at time of study entry were controlled for. CONCLUSIONS: This pilot study suggests clinical and bacteriological advantages of continuous infusion of ceftriaxone over bolus administration in critically ill patients in patients requiring 4 or more days of treatment. This sets the scene for a large multicentre double-blind randomized controlled trial to confirm these findings.
RCT Entities:
OBJECTIVES: To compare the clinical and bacteriological outcome of critically illpatients with sepsis treated by ceftriaxone administered as a once-a-day intermittent bolus dose or by 24 h continuous infusion. PATIENTS AND METHODS: We conducted an open-label, randomized controlled pilot study in 57 patients clinically diagnosed with sepsis (suspected/proven infection and systemic inflammatory response syndrome) in a tertiary level intensive care unit. Patients were randomized to receive 2 g of ceftriaxone administered by once-daily intermittent bolus dosing or by 24 h continuous infusion. Clinical and bacteriological outcomes were assessed by blinded clinicians. RESULTS: Fifty-seven patients were enrolled in the study, 50 of whom fulfilled the a priori definition of treatment for 4 or more days. The infusion (n = 29) and bolus groups (n = 28) were similar in terms of demographics, although the median age of those receiving the infusion was younger. Intention-to-treat analysis found no statistically significant differences in the primary outcomes for clinical response (P = 0.17), clinical cure [infusion n = 13/29 versus bolus n = 5/28; adjusted odds ratio (AOR) = 3.74; 95% confidence interval (95% CI) = 1.11-12.57; P = 0.06], bacteriological response (P = 0.41) and bacteriological cure (infusion n = 18/29 versus bolus 14/28; AOR = 1.64; 95% CI = 0.57-4.70; P = 0.52). However, logistic regression in patients that complied with the a priori definitions who received ceftriaxone by continuous infusion (AOR = 22.8; 95% CI = 2.24-232.3; P = 0.008) or patients with a low Acute Physiology and Chronic Health Evaluation (APACHE) II score (AOR = 0.70; 95% CI = 0.54-0.91; P = 0.008) were associated with an improved clinical outcome when age and Sepsis Organ Failure Assessment (SOFA) score at time of study entry were controlled for. CONCLUSIONS: This pilot study suggests clinical and bacteriological advantages of continuous infusion of ceftriaxone over bolus administration in critically illpatients in patients requiring 4 or more days of treatment. This sets the scene for a large multicentre double-blind randomized controlled trial to confirm these findings.
Authors: Mohd H Abdul-Aziz; Helmi Sulaiman; Mohd-Basri Mat-Nor; Vineya Rai; Kang K Wong; Mohd S Hasan; Azrin N Abd Rahman; Janattul A Jamal; Steven C Wallis; Jeffrey Lipman; Christine E Staatz; Jason A Roberts Journal: Intensive Care Med Date: 2016-01-11 Impact factor: 17.440
Authors: Andrew Ackerman; Nathaniel R Zook; Jeremy F Siegrist; Charles F Brummitt; Margaret M Cook; Thomas J Dilworth Journal: Antimicrob Agents Chemother Date: 2020-05-21 Impact factor: 5.191
Authors: Young R Lee; Pamela D Miller; Saeed K Alzghari; Delilah D Blanco; Jackson D Hager; Kailey S Kuntz Journal: Eur J Drug Metab Pharmacokinet Date: 2018-04 Impact factor: 2.441