A Study of Avycaz (Ceftazidime/Avibactam) Pharmacokinetics/Pharmacodynamics (PK/PD) in Critically Ill Patients

Study Overview
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Brief Summary
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The purpose of this study is to analyze the PK/PD of AvyCaz in critically ill patients in the Intensive Care Unit (12). This study will include medical and post-surgical patients who develop an infection where Avycaz can be utilized. Since these patients will have variable PK parameters, the investigators will also analyze (time-kill) these serum concentrations (ex vivo) against relevant clinical isolates (e.g. GNR with ESBL or KPC) from the ICU to determine microbiologic activity of Avycaz in critically ill patients with variable characteristics. Monte-Carlo simulations will also be conducted against clinical ICU isolates (JMI labs) to help determine appropriate dosing schedules based upon these PK parameters.

Official Title
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A Study of Avycaz (Ceftazidime/Avibactam) Pharmacokinetics/Pharmacodynamics (PK/PD) in Critically Ill Patients

Conditions
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Pharmacokinetics of Avycaz in ICU Patients

Intervention / Treatment
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* Drug: Ceftazidime/avibactam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥18y/o) patients with a medical or post-surgical infection such as skin/soft tissue infections, urinary infections, IA infections and pneumonia (including VAP) Patients requiring intensive care (critically ill patients) in the med/surg ICU (APACHE II score ≥ 15) Patients prescribed Avycaz for their infection will receive FDA recommended dosages and times of administration Written informed consent Exclusion Criteria: Pregnant Patients, patients older than 90 y/o, those with CrCl < 30 mL/min, patients with a BMI > 45 Kg/m2, patients unable to provide serum samples, and those with the risk of imminent death during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Ceftazadime/avibactam<br>Ceftazadime/avibactam 2500 mg (1250 mg for CrCl 31-50 mL/min) IV over 120 minutes, every 8 hours [other antibiotics can also be administered as needed]. Patients will receive at least 3 doses (steady-state) of Avycaz prior to obtaining serum samples. | Drug: Ceftazidime/avibactam<br>* Ceftazadime/avibactam dosing in ICU patients<br>* Other names: Avycaz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean (SD) Ceftazadime/Avibactam Pharmacokinetic (PK) Volume of Distribution Parameter in Intensive Care Patients |  | 2,4,6, 8 hours after receiving the drug | 
| Mean (SD) Ceftazadime/Avibactam Pharmacokinetic Half Life Parameter in Intensive Care Patients |  | 2,4,6, 8 hours after receiving the drug | 
| Mean (SD) Ceftazadime/Avibactam Pharmacokinetic Clearance of Drug Parameter in Intensive Care Patients |  | 2,4,6, 8 hours after receiving the drug | 
| Mean (SD) Ceftazadime/Avibactam Pharmacokinetic Area Under Serum Curve (mg*h/L) Parameter in Intensive Care Patients |  | 2,4,6, 8 hours after receiving the drug | 
| Mean (SD) Ceftazadime/Avibactam Pharmacokinetic (PK) Maximum Serum Concentration in Intensive Care Patients |  | 2,4,6, 8 hours after receiving the drug |