Critically Ill
Conditions
Brief summary
This study evaluates target attainment after either intermittent intravenous bolus or intravenous continuous infusion of cefotaxime in critically ill patients. Critically ill patients will be randomized to intermittent infusion or continuous infusion of cefotaxime.
Detailed description
Critically ill patients have other pharmacokinetic/pharmacodynamic profiles than healthy volunteers. Suboptimal, both under- and overdosing of antibiotics is an important threat in this patient category. Given the time-dependent character of beta-lactam antibiotics continuous dosing as opposed to traditional intermittent dosing is likely to render better target attainment and maintenance and might improve clinical outcome.
Interventions
DRUGCefotaxime
To assess the influence of administration route on target attainment cefotaxime is administered via two IV routes.
Sponsors
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admitted to intensive care * Able to give informed consent by themselves or informed consent can be obtained via next of kin * Indication for treatment with cefotaxime (as judged by treating physician) in the context of our standard treatment protocol of Selective decontamination of the digestive tract (SDD).
Exclusion criteria
* Renal replacement therapy * Contra-indication for cefotaxime, including known or suspected allergy to cefotaxime * No indication for an arterial line; an arterial line will not be placed solely for the purpose of this study; thus, only patients with an indication for an arterial line outside this protocol are eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cefotaxim serum concentrations | 40 min, 1 hour, 2, 4, 8, 12 and 24 hours; 36h; 48 h; 60h; 72h; 84h and 96h post administration | Cefotaxime serum concentrations, total and unbound, will be determined. The Pharmacokinetic/Pharmacodynamic (PK/PD) target of total serum concentration of 4 times above minimal inhibitory concentration (MIC) ascertains that the unbound drug serum concentration will be above the MIC value of 1 mg/mL, which is determined to be the minimum target. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve of cefotaxim | 0-96h post administration | Based on the data from the primary outcome measure a pharmacokinetic model for ICU patients will be developed. |
Countries
Netherlands
Outcome results
None listed