Ceftaroline Pharmacokinetics in Continuous Renal Replacement Therapy

Study Overview
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Brief Summary
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Dosing of ceftaroline in patients with chronic kidney disease is defined, but there is no data on pharmacokinetics and pharmacodynamics of the drug in patients receiving continuous renal replacement therapy (CRRT). The purpose of this study is to determine pharmacokinetics and pharmacodynamics of ceftaroline in a critically ill patient population receiving CRRT, in order to define a dosing recommendation in this population.

Detailed Description
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Ceftaroline fosamil is a time-dependent, hydrophilic, bactericidal fifth generation cephalosporin that was FDA approved in 2010 for community acquired pneumonia and skin and skin structure infections. Ceftaroline is FDA approved for both Gram-positive and Gram-negative organisms. Gram-positive organisms covered are Staphylococcus aureus (methicillin resistant and methicillin sensitive strains), Streptococcus agalactiae, Streptococcus pneumonia, and Streptococcus pyogenes. Gram-negative coverage includes Escherichia coli, Haemophilus influenza, Klebsiella pneumonia, and Klebsiella oxytoca. In order for ceftaroline to exhibit effective bacterial killing, it requires that a certain percentage of the dosing interval is spent above the MIC. Dosing of ceftaroline in patients with chronic kidney disease is defined, but there is no data on pharmacokinetics and pharmacodynamics of the drug in patients receiving continuous renal replacement therapy (CRRT). The purpose of this study is to determine pharmacokinetics and pharmacodynamics of ceftaroline in a critically ill patient population receiving CRRT, in order to define a dosing recommendation in this population. CRRT modes that patients may be receiving in this trial include: continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodialysis (CVVHD), and continuous veno-venous hemodiafiltration (CVVHDF).

Official Title
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Ceftaroline Pharmacokinetics in Critically Ill Patients Receiving Continuous Renal Replacement Therapy

Conditions
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Infection During Renal Replacement Therapy, Critically Ill

Intervention / Treatment
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* Other: Ceftaroline levels in CRRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to an intensive care unit Receiving CRRT (CVVH, CVVHDF, CVVHD) Receiving ceftaroline Exclusion Criteria: Pregnant patients Burn patients Patients with toxic epidermal necrolysis or Stevens-Johnson syndrome Patients prescribed extended infusion ceftaroline

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ceftaroline in CRRT<br>Ceftaroline levels measured in patients receiving continuous renal replacement therapy | Other: Ceftaroline levels in CRRT<br>* Levels of ceftaroline measured in patients receiving CRRT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ceftaroline pharmacokinetics in critically ill patients receiving continuous renal replacement therapy - Half-life | Ceftaroline elimination half-life | 1 year | 
| Ceftaroline pharmacokinetics in critically ill patients receiving continuous renal replacement therapy - Clearance | Ceftaroline clearance | 1 year | 
| Ceftaroline pharmacokinetics in critically ill patients receiving continuous renal replacement therapy - Volume of distribution | Ceftaroline volume of distribution | 1 year | 
| Ceftaroline pharmacokinetics in critically ill patients receiving continuous renal replacement therapy - Sieving coefficient | Continuous renal replacement therapy modality sieving coefficient for ceftaroline | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ceftaroline pharmacodynamics in patients receiving continuous renal replacement therapy | Percentage of time ceftaroline levels are above the minimum inhibitory concentration for the most likely pathogen(s) | 1 year |