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Infections in critically ill patients are a major healthcare problem and an important source of morbidity and mortality. Since critically ill patients often have altered pharmacokinetics (PK) compared to non-critically ill patients there is a substantial risk that present standard dosing regimens of antibiotics lead to suboptimal outcomes for patients on the ICU or the ED. To prevent the risk of inadequate dosing in ICU patients, it is important to fully understand the PK of antibiotics in this vulnerable group in order to optimize the dosing regimens.
With this study, the investigators will describe the pharmacokinetics of cefuroxime and amikacin in ICU and ED patients. A heterogeneous population of ICU and ED patients will be included to be able to find which factors might influence the pharmacokinetics of these drugs and to what extent. By using population modeling the investigators will simulate different dosing regimens and MIC values and compare probability of target attainment between each of these dose and MIC combinations. This will allow the investigators to optimize dosing regimens of cefuroxime and amikacin in critically ill patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cefuroxime/Amikacin | 20 patients will be included in the cefuroxime cohort and 20 patients in the amikacin cohort. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cefuroxime | Drug | Patients receive cefuroxime as part of standard care. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| To describe the population pharmacokinetics of amikacin in Intensive Care or Emergency Department patients | 1 year | |
| To describe the population pharmacokinetics of cefuroxime in Intensive Care or Emergency Department patients | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| To determine the influence of renal clearance and weight on the pharmacokinetics of amikacin and cefuroxime | 1 year | |
| To determine the proportion of patients who attain adequate PK/PD targets in relation to the MIC of the suspected pathogen. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| To investigate to what extend renal replacement therapy affects the pharmacokinetics of amikacin and cefuroxime | 1 year |
Inclusion Criteria:
Exclusion Criteria:
1. Has previously participated in this study.
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Critically ill patients admitted to the ICU or ED.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Julian Machiels, MD, MSc | Contact | +31243614369 | julian.machiels@radboudumc.nl |
| Name | Affiliation | Role |
|---|---|---|
| Roger Brüggemann, Phd | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboudumc intensive care | Recruiting | Nijmegen | Netherlands |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| D001424 | Bacterial Infections |
| D016638 | Critical Illness |
| D007239 | Infections |
| ID | Term |
|---|---|
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D002444 | Cefuroxime |
| D000583 | Amikacin |
| ID | Term |
|---|---|
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 |
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Blood samples and 24 hours urine will be collection following an intravenous gift of either cefuroxime or amikacin.
| Amikacin |
| Drug |
Patients receive amikacin as part of standard care. |
|
| To determine the toxicity of amikacin | 1 year |
| D012769 | Shock |
| D001423 | Bacterial Infections and Mycoses |
| D020969 | Disease Attributes |
| Organic Chemicals |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D007612 | Kanamycin |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |