Imipenem-Relebactam Pharmacokinetics in Augmented Renal Clearance

Inclusion Criteria: * APACHE II score \> 12 and ≤ 35; * Creatinine clearance (CrCL) ≥150 mL/min (as calculated by the Cockcroft-Gault equation using ideal or adjusted body weight) within 24 hours of dosing; * Documented infection or presumed infection as confirmed by the presence of at least one of the following criteria within the past 72 hours: 1. Documented fever (oral, rectal, tympanic, or core temperature \> 38.5° C) 2. Hypothermia (oral, rectal, tympanic, or core temperature \< 35.0° C) 3. An elevated white blood cell (WBC) count ≥ 12,000 cells/mm3 Exclusion Criteria: * If female, currently pregnant or breast feeding; * History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic (Note: mild rash or erythema to penicillin or cephalosporin antibiotics would not disqualify a patient if they have received a carbapenem without problem); * History of chronic kidney disease, hemodialysis, or peritoneal dialysis; or history of acute renal replacement therapy (e.g., hemodialysis, hemofiltration, hemodiafiltration) or extracorporeal membrane oxygenation (ECMO) associated with current illness; * Suspected rhabdomyolysis or creatine kinase \> 10,000 U/L; * Any serum creatinine (SCr) before dosing that is increased ≥ 0.3 mg/dL from the baseline SCr used qualifying for enrollment; * Urinary output \<20 ml/hour for at least 2 hours (oliguria) within 24 hours before enrollment; * Sustained (at least 1 hour) hypotension (systolic pressure \< 90 mmHG or mean arterial pressure \< 55 mmHg) refractory to vasopressors or intravenous fluid resuscitation for at least 24 hours before enrollment; * Significant anemia defined as a hemoglobin \< 8 g/dL at baseline; * Use of probenecid, valproic acid, or imipenem within 3 days before study drug infusion; * Acute liver injury, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 times the upper limit of normal, or AST or ALT \> 3 times the upper limit of normal with an associated total bilirubin \> 2 times upper limit of normal; * Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator); * Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data; * Planned or prior participation in any other interventional drug study within 30 days.