Randomized Trial of Continuous Versus Intermittent Cefotaxime Infusion on ICU.

Study Overview
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Brief Summary
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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
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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.

Official Title
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Does Continuous Cefotaxime Administration Improve Time to Attainment and Maintenance of Target Drug Levels in Critically Ill Patients?

Conditions
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Critically Ill

Intervention / Treatment
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* Drug: Cefotaxime


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intermittent cefotaxime<br>Cefotaxime 1 gram (1000 mg) is to be administered 4 times daily for 4 days | Drug: Cefotaxime<br>* To assess the influence of administration route on target attainment cefotaxime is administered via two IV routes.<br>* Other names: Claforan;|
| Experimental: Continuous cefotaxime<br>After a 1 gram (1000 mg) Cefotaxime loading dose, Cefotaxime 4 gram (4000 mg) is to be administered as a continuous infusion in 24h for 4 days . | Drug: Cefotaxime<br>* To assess the influence of administration route on target attainment cefotaxime is administered via two IV routes.<br>* Other names: Claforan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cefotaxim serum concentrations | 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. | 40 min, 1 hour, 2, 4, 8, 12 and 24 hours; 36h; 48 h; 60h; 72h; 84h and 96h post administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of cefotaxim | Based on the data from the primary outcome measure a pharmacokinetic model for ICU patients will be developed. | 0-96h post administration |