title: Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study.
abstract: OBJECTIVE
  To compare the clinical and bacteriological outcome of critically ill patients with sepsis treated by ceftriaxone administered as a once-a-day intermittent bolus dose or by 24 h continuous infusion.
  
  
  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.
authors.affiliation: Royal Brisbane and Women's Hospital, Brisbane Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Rob
authors.initials: R
authors.lastname: Boots
authors.forename: Claire M
authors.initials: CM
authors.lastname: Rickard
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.forename: Jo
authors.initials: J
authors.lastname: Quinn
authors.forename: Darren M
authors.initials: DM
authors.lastname: Roberts
authors.forename: Brent
authors.initials: B
authors.lastname: Richards
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
mesh_terms: D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000627:therapeutic use; D003422:Critical Care / Q000379:methods*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone