Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial.
- Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial.
P : patients with severe sepsis
E : continuous infusion
C : intermittent bolus
Plasma antibiotic concentrations exceeded the MIC in 82% of patients (18 of 22) in the continuous arm versus 29% (6 of 21) in the intermittent arm (P = .001).
Clinical cure was higher in the continuous group (70% vs 43%; P = .037),
but ICU-free days (19.5 vs 17 days; P = .14) did not significantly differ between groups.
Survival to hospital discharge was 90% in the continuous group versus 80% in the intermittent group (P = .47).
T : prospective, double-blind, randomized controlled trial
Fig and Tab
Fig 1. CONSORT flow diagram.
Fig 2. Free plasma antibiotic concentration between treatment groups on the first sample.
Fig 3. Free plasma antibiotic concentration to minimum inhibitory concentration ratio for 3 samples.
Fig 4. Survival curve for patients in both treatment groups (data has been censored for patients discharged from hospital).
This study has a number of limitations.
Despite treatment groups being largely well balanced, differences existed for some baseline characteristics, such as 6 years younger mean age, 13% more males, 13% higher comorbidity and a 13% higher proportion of pre-ICU infections in the intervention group. A modest sample size in each group may have similarly resulted in potential confounding by unmeasured variables.
In terms of plasma antibiotic concentrations, only trough concentrations were measured. Therefore concentrations at 40-70% T>MIC could only be inferred to be greater than the MIC. A limited number of extreme concentration values in the intermittent group suggested the presence of some sample timing error.