A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE)

Key Inclusion Criteria:

• Cohort 1: APACHE II score between 15 and 30, inclusive; Cohort 2: BSI, HABP, VABPpatients with an APACHE II score ≤30 (cUTI and AP patients do not need to have theirAPACHE II score calculated)

• Positive culture that was collected ≤96 hours prior to randomization indicating a CREinfection, or a high likelihood of a CRE infection

• Diagnosis of BSI as defined by at least one of the following: fever, hypothermia, newonset arterial hypotension, elevated total peripheral white blood cell (WBC) count,increased immature neutrophils (band forms), or leukopenia

• Or, diagnosis of HABP defined as clinical signs and symptoms consistent with pneumoniaacquired after at least 48 hours of continuous stay in an inpatient acute orchronic-care facility, or acquired within 7 days after being discharged from ahospitalization of ≥3 days duration

• Or, diagnosis of VABP defined by clinical signs and symptoms consistent with pneumoniaacquired after at least 48 hours of continuous mechanical ventilation

• Or, diagnosis of cUTI or AP defined by clinical signs and symptoms consistent withcUTI or AP assessed within 24 hours prior to enrollment

Key Exclusion Criteria:

• Cohorts 1 and 2 BSI, HABP, and VABP patients: receipt of more than 72 hours ofpotentially effective antibacterial therapy; Cohort 2: cUTI and AP patients: receiptof any potentially effective antibacterial therapy in the 48 hours prior to enrollment

• Cohort 1 only: knowledge that index CRE infection is resistant to colistin prior torandomization

• Objective clinical evidence for any of the following clinical syndromes thatnecessitates study therapy for greater than 14 days: endovascular infection includingendocarditis, osteomyelitis, prosthetic joint infection, meningitis and/or othercentral nervous system infections

• Objective clinical evidence of infectious involvement of intravascular materialpotentially due to the study qualifying pathogen and not intended to be removed within 4 calendar days of the initial positive culture

• HABP or VABP patients only: pulmonary disease that precludes evaluation of therapeuticresponse including known bronchial obstruction or a history of post-obstructivepneumonia, tracheobronchitis, primary lung cancer or malignancies metastatic to thelung, bronchiectasis, known or suspected active tuberculosis

• cUTI or AP patients only: renal abscess, chronic bacterial prostatitis, orchitis orepididymitis, polycystic kidney disease, one functional kidney, vesicoureteral reflux,renal transplant, cystectomy or ileal loop surgery, fungal UTI or complete, permanentobstruction of the urinary tract

• Patients in acute renal failure at the time of randomization

• Patients receiving intermittent hemodialysis (IHD) at the time of screening

• Pregnant or breastfeeding female patient