Pharmacokinetic Study of Ceftaroline Fosamil/Avibactam in Adults With Augmented Renal Clearance

To evaluate the single-dose pharmacokinetic (PK) profiles of ceftaroline and avibactam
following intravenous (IV) administration of ceftaroline fosamil/avibactam ("CXL") in adults
with augmented renal clearance (ARC).

Inclusion Criteria:

- Male or female adults ≥ 18 and ≤ 55 years old

- Augmented renal clearance, defined as:

- Estimated CrCl ≥ 115 mL/min (calculated using modified Cockcroft-Gault, before
the measured 8-hour urine collection)

- Measured CrCl ≥ 140 mL/min (from an 8-hour urine collection)

- Hospitalized and diagnosed with SIRS, defined by at least 2 of the following:

- Temperature (oral, rectal, tympanic, or core) > 38.5°C or < 35.0°C

- Heart rate > 90 beats/min

- Respiratory rate > 20 breaths/min or PaCO2 < 32 mmHg

- Leukocytosis (> 12,000 white blood cells [WBC]/mm3), leukopenia (< 4000
WBC/mm3), or bandemia (> 10% immature neutrophils [bands] regardless of total
peripheral WBC)

- Requires indwelling urinary bladder catheter per standard of care (through the end of
the 8-hour urine collection)

Exclusion Criteria:

- History of any known hypersensitivity or allergic reaction to cephalosporins or any
β-lactam antimicrobial (eg, penicillins)

- History of chronic kidney disease, hemodialysis, or peritoneal dialysis; or history
of acute renal replacement therapy (eg, hemodialysis, hemofiltration) associated with
current illness

- Suspected rhabdomyolysis or creatine kinase > 10,000 U/L

- Significant anemia defined as hemoglobin < 9 g/dL or hematocrit < 27%

- Transfusion of packed red blood cells (PRBC) or whole blood within 24 hours of study
drug infusion or anticipated need for a transfusion before the last PK blood sample
is collected

- If female, currently pregnant or breastfeeding