Conditions: Bloodstream Infections (BSI) Due to CRE Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE Ventilator-Associated Bacterial Pneumonia (VABP) Due to CRE Complicated Urinary Tract Infection (cUTI) Due to CRE Acute Pyelonephritis (AP) Due to CRE
Keywords: Gram-negative bacterial infection antibacterial antimicrobial CRE CPE BSI pneumonia HABP VABP AP cUTI UTI
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 69
Healthy volunteers: no

Brief summary:
This was a Phase 3 study containing a randomized open-label superiority cohort (Cohort 1) comparing the efficacy and safety of plazomicin with colistin when combined with a second antibiotic (either meropenem or tigecycline) in the treatment of patients with bloodstream infection (BSI), hospital acquired bacterial pneumonia (HABP), or ventilator-associated bacterial pneumonia (VABP) due to CRE. An additional cohort of patients with BSI, HABP, VABP, complicated urinary tract infection (cUTI), or acute pyelonephritis (AP) due to CRE, not eligible for inclusion in the other cohort, were enrolled into a single arm (Cohort 2) and treated with plazomicin-based therapy. Therapeutic drug management (TDM) was used to help ensure that plazomicin exposures lie within an acceptable range of the target mean steady-state area under the curve (AUC).

Detailed description:

Arms:
arm 1: Cohort 1: Patients received 15 milligram per killogram (mg/kg) plazomicin therapy (plus meropenem or tigecycline) as a 30-minute intravenous (IV) infusion once daily for 7 to 14 days. arm 2: Cohort 1: Patients received a 5 mg/kg IV loading dose (300 mg maximum) colistin (plus meropenem or tigecycline) followed by a 5 mg/kg/d maintenance dose divided into every 8 hours (q8h) or every 12 hours (q12h) for 7 to 14 days. arm 3: Cohort 2: Patients received 15 mg/kg as a 30 minute IV infusion once daily. BSI, HABP or VABP patients received plazomicin and any supplemental antibiotic therapy, according to Investigator's choice, for 7 to 14 days. cUTI or AP patients received plazomicin monotherapy only for 4 to 7 days with an option to switch to oral therapy on or after Day 5.

Interventions: intervention 1: plazomicin intervention 2: colistin intervention 3: meropenem intervention 4: tigecycline intervention 5: antibiotic of Investigator's choice
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None

Protocol document: