Trial Outcomes & Findings for A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE) (NCT NCT01970371)

NCT ID: NCT01970371

Last Updated: 2018-10-16

Results Overview

ACM at Day 28: confirmed date of death within 28 days of the first dose of study drug, irrespective of causality. SDRCs for all patients: presence of 1 or more of the following complications within 7 days of randomization: new or worsening acute respiratory distress syndrome (ARDS), new lung abscess, new empyema, new onset of septic shock, new carbapenem-resistant Enterobacteriaceae (CRE) (HABP/VABP patients only); persistent bacteremia on study Day ≥5 (BSI patients only). Note: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and statistical analysis plan (SAP).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 69 participants
• Primary outcome timeframe: Up to Day 28 for ACM, up to 7 Days for SDRCs in all patients, on or after Day 5 for BSI patients only.
• Results posted on: 2018-10-16

Participant Flow

Participant milestones

Measure	Plazomicin in Combination With Meropenem or Tigecycline 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.	Colistin in Combination With Meropenem or Tigecycline 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.	Plazomicin in Combination With Adjunctive Antibiotic Cohort 2: Patients received 15 mg/kg as a 30 minute IV infusion once daily. Bloodstream infection (BSI), hospital acquired bacterial pneumonia (HABP), or ventilator associated bacterial pneumonia (VABP) patients received plazomicin and any supplemental antibiotic therapy, according to Investigator's choice, for 7 to 14 days. Complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) patients received plazomicin monotherapy only for 4 to 7 days with an option to switch to oral therapy on or after Day 5.
Overall Study STARTED	18	21	30
Overall Study COMPLETED	10	8	17
Overall Study NOT COMPLETED	8	13	13

Reasons for withdrawal

Measure	Plazomicin in Combination With Meropenem or Tigecycline 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.	Colistin in Combination With Meropenem or Tigecycline 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.	Plazomicin in Combination With Adjunctive Antibiotic Cohort 2: Patients received 15 mg/kg as a 30 minute IV infusion once daily. Bloodstream infection (BSI), hospital acquired bacterial pneumonia (HABP), or ventilator associated bacterial pneumonia (VABP) patients received plazomicin and any supplemental antibiotic therapy, according to Investigator's choice, for 7 to 14 days. Complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) patients received plazomicin monotherapy only for 4 to 7 days with an option to switch to oral therapy on or after Day 5.
Overall Study Death	8	13	12
Overall Study Lost to Follow-up	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=18 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=21 Participants 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic n=30 Participants 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.	Total n=69 Participants Total of all reporting groups
Age, Continuous	64.94 years STANDARD_DEVIATION 13.94 • n=5 Participants	63.29 years STANDARD_DEVIATION 18.25 • n=7 Participants	62.8 years STANDARD_DEVIATION 18.15 • n=5 Participants	63.51 years STANDARD_DEVIATION 16.97 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	11 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants	45 Participants n=4 Participants
Race/Ethnicity, Customized White	16 Participants n=5 Participants	17 Participants n=7 Participants	29 Participants n=5 Participants	62 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Other Unspecified	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	13 Participants n=5 Participants	18 Participants n=7 Participants	29 Participants n=5 Participants	60 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to Day 28 for ACM, up to 7 Days for SDRCs in all patients, on or after Day 5 for BSI patients only.

Population: The mMITT population was a subset of the MITT population and included all patients who received ≥1 dose of study drug and had a CRE pathogen. CRE=meropenem minimum inhibitory concentration (MIC) of ≥4 micrograms per milliliter (μg/mL) or meropenem MIC=2 μg/mL and disk diffusion results (≤19 millimetres \[mm\]) indicating meropenem resistance.

ACM at Day 28: confirmed date of death within 28 days of the first dose of study drug, irrespective of causality. SDRCs for all patients: presence of 1 or more of the following complications within 7 days of randomization: new or worsening acute respiratory distress syndrome (ARDS), new lung abscess, new empyema, new onset of septic shock, new carbapenem-resistant Enterobacteriaceae (CRE) (HABP/VABP patients only); persistent bacteremia on study Day ≥5 (BSI patients only).

Note: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and statistical analysis plan (SAP).

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=17 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=20 Participants 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic 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.
Percentage of Patients With All Cause Mortality (ACM) at Day 28 or Significant Disease-Related Complication (SDRC) in the Microbiological Modified Intent to Treat (mMITT) Population in Cohort 1	23.5 percentage of patients	50 percentage of patients	—

SECONDARY outcome

Timeframe: Up to Day 28

Population: The mMITT population was a subset of MITT population and included all patients who received at least 1 dose of study drug and had a CRE pathogen. CRE=meropenem MIC of ≥4 μg/mL or meropenem MIC=2 μg/mL and disk diffusion results (≤19 mm) indicating meropenem resistance.

ACM at Day 28: confirmed date of death within 28 days of the first dose of study drug, irrespective of causality.

Note: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and SAP.

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=17 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=20 Participants 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic 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.
Percentage of Patients With ACM at Day 28 in the mMITT Population in Cohort 1	11.8 percentage of patients	40 percentage of patients	—

SECONDARY outcome

Timeframe: Up to TOC (Day 23)

Population: The mMITT population was a subset of MITT population and included all patients who received at least 1 dose of study drug and had a CRE pathogen. CRE=meropenem MIC of ≥4 μg/mL or meropenem MIC=2 μ/mL and disk diffusion results (≤19 mm) indicating meropenem resistance.

Clinical response (CR) was assessed at end of treatment (EOT) in all patients and at TOC for those who were a clinical cure or had an indeterminate outcome at the most recent visit. Assessment of CR at TOC was not needed for those who were a clinical failure at an earlier visit. Clinical outcomes at both EOT and TOC were independently adjudicated by an external committee. The assessment was confounded by comorbidities and the occurrence of additional infections; thus, adjudicating CR of the baseline CRE infection was influenced by confounding signs and symptoms of unrelated infections or conditions. The difficulty assessing CR supports greater reliance on the more objective mortality-based primary endpoint in these patients.

Note: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the endpoints per the protocol and SAP.

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=17 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=20 Participants 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic 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.
Percentage of Patients With Adjudicated Clinical Cure at the Test of Cure (TOC) Visit in the mMITT Population in Cohort 1 EOT Visit: Clinical Cure	64.7 percentage of patients	45 percentage of patients	—
Percentage of Patients With Adjudicated Clinical Cure at the Test of Cure (TOC) Visit in the mMITT Population in Cohort 1 EOT Visit: Clinical Failure	35.3 percentage of patients	55 percentage of patients	—
Percentage of Patients With Adjudicated Clinical Cure at the Test of Cure (TOC) Visit in the mMITT Population in Cohort 1 TOC Visit: Clinical Cure	35.3 percentage of patients	35 percentage of patients	—
Percentage of Patients With Adjudicated Clinical Cure at the Test of Cure (TOC) Visit in the mMITT Population in Cohort 1 TOC Visit: Clinical Failure	58.8 percentage of patients	65 percentage of patients	—
Percentage of Patients With Adjudicated Clinical Cure at the Test of Cure (TOC) Visit in the mMITT Population in Cohort 1 TOC Visit: Indeterminate Response	5.9 percentage of patients	0 percentage of patients	—

SECONDARY outcome

Timeframe: Up to Day 28

Population: The mMITT population included all patients who received at least 1 dose of study drug and had a CRE pathogen. CRE=meropenem MIC of ≥4 μg/mL or meropenem MIC=2 μg/mL and disk diffusion results (≤19 mm) indicating meropenem resistance.

Time to death through Day 28 is defined as days from first dose of study drug to death from any cause on or before Day 28. Patients who were alive at Day 28 were censored on Day 28. Any patient whose survival status was not known at Day 28 was censored on the last known date alive.

Note: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and SAP.

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=17 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=20 Participants 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic 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.
Time to Death Through Day 28 in the mMITT Population in Cohort 1 % of patients who died by Day 28	11.8 percentage of patients	40.0 percentage of patients	—
Time to Death Through Day 28 in the mMITT Population in Cohort 1 % of patients censored at 28 days	88.2 percentage of patients	60.0 percentage of patients	—
Time to Death Through Day 28 in the mMITT Population in Cohort 1 % of patients censored at <28 days	0.0 percentage of patients	0.0 percentage of patients	—
Time to Death Through Day 28 in the mMITT Population in Cohort 1 Kaplan-Meier estmate of ACM at Day 28	11.8 percentage of patients	40 percentage of patients	—

SECONDARY outcome

Timeframe: Day 14

Population: The mMITT population was a subset of MITT population and included all patients who received ≥1 dose of study drug and had a CRE pathogen. CRE=meropenem MIC of ≥4 μg/mL or meropenem MIC=2 μg/mL and disk diffusion results (≤19 mm) indicating meropenem resistance.

ACM at Day 14 was defined as a confirmed date of death within 14 days of the first dose of study drug, irrespective of causality.

Note: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 2 are not presented here as this Cohort was not part of the primary or key secondary endpoints per the protocol and SAP.

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=17 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=20 Participants 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic 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.
Percentage of Patients With ACM at Day 14 in the mMITT Population in Cohort 1	5.9 percentage of patients	20 percentage of patients	—

SECONDARY outcome

Timeframe: Up to Day 14

Population: The safety population included all randomized patients who received any amount of study drug.

After the initial plazomicin dose, subsequent doses were adjusted, as directed, with the use of TDM on Day 1, 4, and 8 as needed.

Note: Although it is generally expected that results for primary and secondary endpoints will be presented for all arms included at baseline, results for Cohort 1: Colistin are not presented here as TDM collection does not apply to and was not collected for patients in the colistin arm, as only plazomicin levels were measured.

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=18 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=30 Participants 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic 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.
Percentage of Patients With Dose Adjustment Due to Therapeutic Drug Management (TDM)	77.8 percentage of patients	86.7 percentage of patients	—

SECONDARY outcome

Timeframe: Up to Day 67

Population: The safety population included all randomized patients who received any amount of study drug.

An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered to be drug related. An AE (also referred to as an adverse experience) can be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, and it does not imply any judgment about causality. Adverse events also include the exacerbation or worsening of a condition present at screening other than the index infection for which the patient was enrolled in the study. A TEAE is any AE that newly appeared, increased in frequency, or worsened in severity following initiation of study drug. The safety population included all randomized patients who received any amount of study drug.

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=18 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=21 Participants 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic n=30 Participants 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.
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs)	88.9 percentage of patients	100 percentage of patients	86.7 percentage of patients

SECONDARY outcome

Timeframe: 48 hours

Population: PK population included all patients who had received at least 1 dose of plazomicin and had at least 1 quantifiable plazomicin plasma concentration available for analysis.

PK specimens were collected on Days 1 and 4 using a sparse sampling scheme, and concentration-time data from these PK specimens were pooled with data from specimens collected for TDM. The pooled data were analyzed by population PK modeling, which described PK over the entire course of plazomicin treatment. The protocol allowed dose adjustments based on creatinine clearance; therefore, various dose regimens were used in the study, including regimens with dosing intervals of 12, 24, and 48 hours. To enable a combined summation of exposures across dose regimens, PK exposure parameters for the study were summarized for the first 48 hours of treatment. Thus, while exposures are summarized for the first 48 hours, the reported results considered patient data over the course of plazomicin treatment.

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=48 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic 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.
Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h)	235 mg*h/L (millgrams times hours per liter) Geometric Coefficient of Variation 42	—	—

SECONDARY outcome

Timeframe: 48 hours

Population: PK population included all patients who had received at least 1 dose of plazomicin and had at least 1 quantifiable plazomicin plasma concentration available for analysis.

PK specimens were collected on Days 1 and 4 using a sparse sampling scheme, and concentration-time data from these PK specimens were pooled with data from specimens collected for TDM. The pooled data were analyzed by population PK modeling, which described PK over the entire course of plazomicin treatment. The protocol allowed dose adjustments based on creatinine clearance; therefore, various dose regimens were used in the study, including regimens with dosing intervals of 12, 24, and 48 hours. To enable a combined summation of exposures across dose regimens, PK exposure parameters for the study were summarized for the first 48 hours of treatment. Thus, while exposures are summarized for the first 48 hours, the reported results considered patient data over the course of plazomicin treatment.

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=48 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic 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.
Plasma Pharmacokinetics (PK): Maximum Observed Plasma Drug Concentration (Cmax)	37.1 mg/L Geometric Coefficient of Variation 39.3	—	—

SECONDARY outcome

Timeframe: 48 hours

Population: PK population included all patients who had received at least 1 dose of plazomicin and had at least 1 quantifiable plazomicin plasma concentration available for analysis.

PK specimens were collected on Days 1 and 4 using a sparse sampling scheme, and concentration-time data from these PK specimens were pooled with data from specimens collected for TDM. The pooled data were analyzed by population PK modeling, which described PK over the entire course of plazomicin treatment. The protocol allowed dose adjustments based on creatinine clearance; therefore, various dose regimens were used in the study, including regimens with dosing intervals of 12, 24, and 48 hours. To enable a combined summation of exposures across dose regimens, PK exposure parameters for the study were summarized for the first 48 hours of treatment. Thus, while exposures are summarized for the first 48 hours, the reported results considered patient data over the course of plazomicin treatment.

Outcome measures

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=48 Participants Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic 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.
Plasma Pharmacokinetics (PK): Minimum Observed Plasma Drug Concentration (Cmin)	2.1 mg/L Geometric Coefficient of Variation 99.4	—	—

Adverse Events

Plazomicin in Combination With Meropenem or Tigecycline

Serious events: 9 serious events

Other events: 13 other events

Deaths: 8 deaths

Colistin in Combination With Meropenem or Tigecycline

Serious events: 17 serious events

Other events: 20 other events

Deaths: 13 deaths

Plazomicin in Combination With Adjunctive Antibiotic

Serious events: 20 serious events

Other events: 22 other events

Deaths: 12 deaths

Serious adverse events

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=18 participants at risk Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=21 participants at risk 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic n=30 participants at risk 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.
Vascular disorders Deep vein thrombosis	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Vascular disorders Haemodynamic instability	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Vascular disorders Orthostatic hypotension	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
General disorders Multiple organ dysfunction syndrome	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Injury, poisoning and procedural complications Pneumonitis chemical	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Investigations Blood creatinine increased	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Cardiac disorders Acute myocardial infarction	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Cardiac disorders Cardiac Arrest	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	13.3% 4/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Cardiac disorders Cardio-respiratory arrest	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Nervous system disorders Cerebral ischaemia	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Nervous system disorders Cerebrovascular accident	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Gastrointestinal disorders Intra-abdominal haemorrhage	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Renal and urinary disorders Acute kidney injury	11.1% 2/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	14.3% 3/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Renal and urinary disorders Renal failure	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Metabolism and nutrition disorders Hyperosmolar state	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Endocarditis	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Hepatitis infectious	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Infection	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Lung infection	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Pneumonia	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Pneumonia necrotising	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Pseudomonal bacteraemia	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Sepsis	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	14.3% 3/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Septic shock	22.2% 4/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	23.8% 5/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	16.7% 5/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Urinary tract infection	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	13.3% 4/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.

Other adverse events

Measure	Plazomicin in Combination With Meropenem or Tigecycline n=18 participants at risk Cohort 1: Patients received 15 mg/kg plazomicin therapy (plus meropenem or tigecycline) as a 30-minute IV infusion once daily for 7 to 14 days.	Colistin in Combination With Meropenem or Tigecycline n=21 participants at risk 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 q8h or q12h for 7 to 14 days.	Plazomicin in Combination With Adjunctive Antibiotic n=30 participants at risk 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.
Renal and urinary disorders Acute kidney injury	11.1% 2/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	19.0% 4/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	16.7% 5/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Vascular disorders Hypotension	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	10.0% 3/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
General disorders Pyrexia	11.1% 2/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Psychiatric disorders Delirium	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	10.0% 3/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Psychiatric disorders Depression	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Investigations Blood bilirubin increased	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Investigations Blood creatinine increased	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Investigations Blood fibrinogen decreased	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Investigations International normalised ratio increased	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Cardiac disorders Atrial fibrillation	11.1% 2/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Cardiac disorders Extrasystoles	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Blood and lymphatic system disorders Anaemia	22.2% 4/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Blood and lymphatic system disorders Leukocytosis	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Blood and lymphatic system disorders Thrombocytopenia	11.1% 2/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Respiratory, thoracic and mediastinal disorders Pneumothorax	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Gastrointestinal disorders Constipation	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Gastrointestinal disorders Diarrhoea	11.1% 2/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	10.0% 3/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Gastrointestinal disorders Nausea	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	10.0% 3/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Gastrointestinal disorders Vomiting	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Hepatobiliary disorders Jaundice	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Renal and urinary disorders Renal impairment	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Skin and subcutaneous tissue disorders Dermatitis allergic	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Skin and subcutaneous tissue disorders Penile ulceration	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Skin and subcutaneous tissue disorders Pruritus generalised	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Metabolism and nutrition disorders Dehydration	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Metabolism and nutrition disorders Hypernatraemia	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Metabolism and nutrition disorders Hypomagnesaemia	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Metabolism and nutrition disorders Hypokalaemia	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Metabolism and nutrition disorders Hyponatraemia	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	6.7% 2/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Bacteraemia	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Fungal sepsis	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Oral fungal infection	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Lower respiratory tract infection	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Pneumonia	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	9.5% 2/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Sepsis	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	3.3% 1/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Skin infection	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Stoma site abscess	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Systemic candida	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Tinea cruris	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Infections and infestations Tracheobronchitis	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	4.8% 1/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.
Renal and urinary disorders Haematuria	5.6% 1/18 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/21 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.	0.00% 0/30 • Up to Day 67 The safety population included all randomized patients who received any amount of IV study drug. Because of the small sample size enrolled and the requirement to report AEs occurring in ≥5% of patients, all AEs are reported here, including those occurring in only a single patient.

Additional Information

Clinical Trials Registration Group

Achaogen, Inc.

Email: clinical-trials@achaogen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Investigator may publish/present the study results provided all of the following: (i) the primary publication has been published; or, if no such publication has occurred, at least 18m have passed since the completion of the study; (ii) Achaogen is allowed at least 60d to review; (iii) confidential information is deleted as requested; (iv) comments and proposed revisions are considered; and (v) during the 60d review, if requested, the Investigator shall delay the publication or presentation.
• Publication restrictions are in place

Restriction type: OTHER