Pharmacokinetics of Ceftolozane/Tazobactam in Patients With Burns

A single dose pharmacokinetic study of ceftolozane and tazobactam will be conducted in
patients with burns at the Burn Center at University Medical Center. A total of 12 adults
aged 18 to 80 years with >/= 20% percent total body surface area burned will be required to
complete the study. A single intravenous dose of ceftolozane and tazobactam of 2 grams/1 gram
will be administered over 60 minutes and whole blood will be obtained predose and at 0.5, 1,
1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours following the start of infusion. Urine samples
(5 ml) will be collected from a urine collection bag (if the patient has urinated) at the
following timepoints: 0-0.5, 0.5-1, 1-2, 2-4, 4-8, 8-12, and 12-24 hours for analysis of
ceftolozane and tazobactam content. Urine for collected during each time period will be
measured to determine urine volume for urine clearance calculations. The volume of urine in
the urine over the entire 24 hour period and an aliquot sent for analysis of urine creatinine
content to determine the patient's 24 hour creatinine clearance.

Inclusion Criteria:

1. Male and female subjects, ages 18-80 years, of all racial and ethnic origins.

2. Non-English Spanish speakers will be included in the study.

3. We are recruiting 12 patients with thermal burn injuries (percent total body surface
area burned >/= 20%). Patients will be at least five days from the date of the burn
injury.

4. Patients will have central venous or arterial line access.

5. Patients will be already be receiving standard of care antimicrobial therapy for a
suspected infection.

Exclusion Criteria:

1. Pregnant or nursing or unwilling to use a reliable contraception method during the
study. The effects of ceftolozane and tazobactam on pregnancy are unknown. In
addition, the metabolic changes that accompany pregnancy may alter the
concentration-time profile of ceftolozane and tazobactam, so that the pregnancy and
post-partum state would be a confounding variable.

2. Abnormal liver function tests: transaminases >10 times upper limit of normal, Alkaline
phosphatase >5 times upper limit of normal, total bilirubin >5 times upper limit of
normal.

3. History of allergies to beta-lactam antibiotics.

4. Patients unwilling to comply with study procedures.

5. Current or previous participation within 28 days of enrollment in another research
study that involves the use of medication, contrast, or any other compound that may
alter blood count and/or blood chemistry (liver function, kidney function or
electrolyte balance), unless waved by principal investigator (PI).

6. Donation of 450mL (one unit) of blood or more within 8 weeks (56 days) prior to study
enrollment, unless waved by PI.

7. Creatinine clearance < 30 ml/min as estimated by the Cockcroft-Gault equation.

8. Patients who are receiving piperazillin/tazobactam or have received
piperacillin/tazobactam within the past 48 hours.

9. Patients who are receiving vasopressors.

10. Patients with a total body weight < 60 kg or > 130 kg.