Pharmacokinetic and Pharmacodynamic Analysis of Ceftaroline in Children and Adolescents With Cystic Fibrosis

Study Overview
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Brief Summary
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This is an open-label, single center, prospective study of patients with a diagnosis of cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus (MRSA), also known as oxacillin-resistant Staphylococcus aureus (ORSA), being treated with intravenous ceftaroline. Patients will have intravenous ceftaroline dosed according to current recommendations based upon its approved usage in pediatric patients for community acquired pneumonia. The investigators will analyze pharmacokinetic (PK) and pharmacodynamic (PD) data using serum concentrations of ceftaroline measured at various time-points following infusion of ceftaroline to develop PK/PD guided dosing strategies of ceftaroline in pediatric CF patients that would be tailored to account for bacterial susceptibility and disease progression.

Detailed Description
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This is an open-label, single center, prospective study of patients with a diagnosis of cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus (MRSA), also known as oxacillin-resistant Staphylococcus aureus (ORSA), being treated with intravenous ceftaroline. Patients will have intravenous ceftaroline dosed according to current recommendations based upon its approved usage in pediatric patients for community acquired pneumonia. The investigators will analyze pharmacokinetic (PK) and pharmacodynamic (PD) data using serum concentrations of ceftaroline measured at various time-points following infusion of ceftaroline to develop PK/PD guided dosing strategies of ceftaroline in pediatric CF patients that would be tailored to account for bacterial susceptibility and disease progression and determine if current dosing regimes used are appropriate for this patient population. Blood samples will be collected prior to infusion of ceftaroline and at approximately 1 hour (+/- 10 minutes), 1.5 hours (+/- 10 minutes), 3 hours (+/- 30 minutes), and 6 hours (+/- 30 minutes) after initiation of infusion. The blood samples (0.5 to 1 ml) will be collected through intravenous access, venipuncture, or capillary blood puncture. Samples will be centrifuged at 1500g at 4°C for 15 minutes within 15 minutes of collection. Serum will be separated into two aliquots of a minimum of 0.2 mL and stored at -70°C until analysis. Determination of serum ceftaroline concentrations will be measured using high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Key clinical data (PK/PD) that will be collected includes age, sex, genotype, growth parameters, airway microbiology, sweat chloride values, pulmonary function test (FEV1), concomitant medications, and comorbid disorders (i.e.: CF related diabetes, CF liver disease, short gut, renal dysfunction, pulmonary hypertension, coagulopathy).

Official Title
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Pharmacokinetic and Pharmacodynamic Analysis of Ceftaroline in Children and Adolescents With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Ceftaroline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cystic Fibrosis diagnosis on accepted Cystic Fibrosis Foundation guidelines Inpatient Decision by treating physician to use intravenous ceftaroline Exclusion Criteria: less than 2 years old 22 years of age or older less than 15 kg weight Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 5 fold upper limit of normal Gamma-glutamyltransferase (GGT) > 3 fold above upper limit of normal Total bilirubin > 2 mg/dL Platelets < 50,000 Patients without documented CF Non-English speaking patients/families

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 21 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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single center, prospective study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: PK/PD<br>Open-label prospective study with participants receiving treating physician-approved intravenous ceftaroline, dosed according to current recommendations. Blood samples collected at baseline, 1 hour, 1.5 hours, 3 hours, and 6 hours after infusion. | Drug: Ceftaroline<br>* Patients will have intravenous ceftaroline dosed according to current recommendations based upon its approved usage in pediatric patients for community acquired pneumonia. Blood samples will be collected for PK/PD analysis.<br>* Other names: Ceftaroline fosamil,Teflaro, Zinforo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ceftaroline Exposure and PK/PD Target Attainment | Interpret PK/PD target attainment based on percent time of the free ceftaroline concentration (=PK) above minimum inhibitory concentration (=PD index) | 12-hour maximum, single visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 Percentage Change Assessment | Assess change in FEV1 percent predicted during ceftaroline treatment | 12-hour maximum, single visit | 
| Treatment Failures | Assess any treatment failures as evidenced by provider documentation (including FEV1 not improving and/or change in antimicrobial drugs) | 12-hour maximum, single visit | 
| Side Effects | Assess for side effects as documented by providers | 12-hour maximum, single visit | 
| Pulmonary Exacerbations | Assess for time until next pulmonary exacerbation | 12-hour maximum, single visit |