Pharmacokinetics of Amikacin and Cefuroxime in Critically Ill Patients.

Study Overview
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Brief Summary
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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.

Official Title
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Population Pharmacokinetics of Amikacin and Cefuroxime in Critically Ill Septic Patients Admitted to the ICU or the ED

Conditions
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Sepsis, Septic Shock, Infection, Bacterial, Critically Ill

Intervention / Treatment
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* Drug: Cefuroxime
* Drug: Amikacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is admitted to the ICU or ED; The patient is at least 18 years of age on the day of inclusion; Is managed with a central venous catheter or arterial line; Is treated with amikacin and/or cefuroxime as standard care. Exclusion Criteria: 1. Has previously participated in this study.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cefuroxime/Amikacin<br>20 patients will be included in the cefuroxime cohort and 20 patients in the amikacin cohort. | Drug: Cefuroxime<br>* Patients receive cefuroxime as part of standard care.<br>Drug: Amikacin<br>* Patients receive amikacin as part of standard care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| To determine the toxicity of amikacin |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Septic Shock, Infection, Critically Ill