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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intermittent cefotaxime | Active Comparator | Cefotaxime 1 gram (1000 mg) is to be administered 4 times daily for 4 days |
|
| Continuous cefotaxime | Experimental | 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 . |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cefotaxime | Drug | To assess the influence of administration route on target attainment cefotaxime is administered via two IV routes. |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jan G Zijlstra, MD, PhD | Department of Critical Care, UMCG | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Groningen | Provincie Groningen | 9700 RB | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31697336 | Derived | Aardema H, Bult W, van Hateren K, Dieperink W, Touw DJ, Alffenaar JC, Zijlstra JG. Continuous versus intermittent infusion of cefotaxime in critically ill patients: a randomized controlled trial comparing plasma concentrations. J Antimicrob Chemother. 2020 Feb 1;75(2):441-448. doi: 10.1093/jac/dkz463. |
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| ID | Term |
|---|---|
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D002439 | Cefotaxime |
| ID | Term |
|---|---|
| D002505 | Cephacetrile |
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 |
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|
| Amides |
| D009930 | Organic Chemicals |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |