Trial Outcomes & Findings for Compare Ceftazidime-Avibactam + Metronidazole vs Meropenem for Hospitalized Adults With Complicated Intra-Abd Infections (NCT NCT01726023)

Results Overview

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

486 participants

Primary outcome timeframe

At the test of cure visit (Day 28 to35)

Results posted on

2017-09-06

Participant Flow

Overall, 486 patients were enrolled from 43 centers in 3 countries in this study. The first patient was enrolled on 14 January 2013 and the last patient last visit was on 14 March 2015.

Of 486 enrolled patients, 42 did not meet the eligibility criteria. A further two patients were not randomized due to withdrawn consent, and one patient was not randomized due to unavailability of study drug.

Participant milestones

Participant milestones
Measure	Ceftazidime-Avibactam Plus Metronidazole Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem Meropenem powder for solution for infusion 1000mg
Overall Study STARTED	219	222
Overall Study COMPLETED	190	196
Overall Study NOT COMPLETED	29	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Ceftazidime-Avibactam Plus Metronidazole Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem Meropenem powder for solution for infusion 1000mg
Overall Study Death	1	1
Overall Study Lost to Follow-up	5	10
Overall Study Other Eligibility criteria	7	7
Overall Study Withdrawal by Subject	16	8

Baseline Characteristics

Compare Ceftazidime-Avibactam + Metronidazole vs Meropenem for Hospitalized Adults With Complicated Intra-Abd Infections

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ceftazidime-Avibactam Plus Metronidazole n=214 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=217 Participants Meropenem powder for solution for infusion 1000mg	Total n=431 Participants Total of all reporting groups
Age, Continuous	48.5 Years STANDARD_DEVIATION 16.83 • n=5 Participants	48.5 Years STANDARD_DEVIATION 17.43 • n=7 Participants	48.5 Years STANDARD_DEVIATION 17.11 • n=5 Participants
Age, Customized 18-45 Years	89 Participants n=5 Participants	96 Participants n=7 Participants	185 Participants n=5 Participants
Age, Customized 46-64 Years	85 Participants n=5 Participants	72 Participants n=7 Participants	157 Participants n=5 Participants
Age, Customized 65-74 Years	28 Participants n=5 Participants	30 Participants n=7 Participants	58 Participants n=5 Participants
Age, Customized 75-90 Years	12 Participants n=5 Participants	19 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Female	73 Participants n=5 Participants	64 Participants n=7 Participants	137 Participants n=5 Participants
Sex: Female, Male Male	141 Participants n=5 Participants	153 Participants n=7 Participants	294 Participants n=5 Participants
Race/Ethnicity, Customized Asian	214 Participants n=5 Participants	217 Participants n=7 Participants	431 Participants n=5 Participants

PRIMARY outcome

Timeframe: At the test of cure visit (Day 28 to35)

Population: The clinically evaluable (CE) analysis set included all patients who met the disease definition of cIAI and met the stringent criteria for clinical evaluation described in the protocol regarding dosing, concomitant medication, evaluation, etc.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=177 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=184 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) Analysis Set. Clinical cure	166 Number of patients	173 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) Analysis Set. Clinical failure	11 Number of patients	11 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=106 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=118 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. Clinical cure	103 Number of patients	113 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. Clinical failure	3 Number of patients	5 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=99 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=113 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. Clinical cure	92 Number of patients	107 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. Clinical failure	7 Number of patients	6 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the late follow up (LFU) (Day 42 to 49)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=96 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=106 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. Clinical cure	89 Number of patients	100 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. Clinical failure	7 Number of patients	6 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=107 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=125 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Clinical cure	104 Number of patients	120 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Clinical failure	3 Number of patients	5 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=100 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=119 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Clinical cure	93 Number of patients	113 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Clinical failure	7 Number of patients	6 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the late follow up (LFU) (Day 42 to 49)

Population: Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=97 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=112 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Clinical cure	90 Number of patients	106 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Clinical failure	7 Number of patients	6 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: The microbiological modified intent-to-treat mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=143 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=152 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Clinical cure	126 Number of patients	140 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Clinical failure	6 Number of patients	7 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Indeterminate	11 Number of patients	5 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: The microbiological modified intent-to-treat mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=143 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=152 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Clinical cure	119 Number of patients	135 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Clinical failure	10 Number of patients	9 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Indeterminate	14 Number of patients	8 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the late follow up (LFU) (Day 42 to 49)

Population: The microbiological modified intent-to-treat mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=143 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=152 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Clinical cure	116 Number of patients	132 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Clinical failure	10 Number of patients	9 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Indeterminate	17 Number of patients	11 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: The clinically evaluable (CE) analysis set included all patients who met the disease definition of cIAI and met the stringent criteria for clinical evaluation described in the protocol regarding dosing, concomitant medication, evaluation, etc.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=190 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=196 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Clinically Evaluable (CE) Analysis Set. Clinical cure	183 Number of patients	187 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Clinically Evaluable (CE) Analysis Set. Clinical failure	7 Number of patients	9 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At late follow up (LFU) visits (Day 42 to 49)

Population: The clinically evaluable (CE) analysis set included all patients who met the disease definition of cIAI and met the stringent criteria for clinical evaluation described in the protocol regarding dosing, concomitant medication, evaluation, etc.

The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=168 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=179 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Clinically Evaluable (CE) Analysis Set. Clinical cure	157 Number of patients	168 Number of patients	—	—	—	—
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Clinically Evaluable (CE) Analysis Set. Clinical failure	11 Number of patients	11 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=106 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=118 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. Favorable	103 Number of patients	113 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. Unfavorable	3 Number of patients	5 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=99 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=113 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. Favorable	92 Number of patients	107 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. Unfavorable	7 Number of patients	6 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the late follow up (LFU) (Day 42 to 49)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=96 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=106 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. Favorable	89 Number of patients	100 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. Unfavorable	7 Number of patients	6 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=107 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=125 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Favorable	104 Number of patients	120 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Unfavorable	3 Number of patients	5 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=100 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=119 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Favorable	93 Number of patients	113 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Unfavorable	7 Number of patients	6 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the late follow up (LFU) (Day 42 to 49)

Population: Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=97 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=112 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Favorable	90 Number of patients	106 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Unfavorable	7 Number of patients	6 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: The microbiological modified intent-to-treat (mMITT) analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=143 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=152 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Favorable	126 Number of patients	140 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Unfavorable	6 Number of patients	7 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Indeterminate	11 Number of patients	5 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: The microbiological modified intent-to-treat (mMITT) analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=143 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=152 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Favorable	119 Number of patients	135 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Unfavorable	10 Number of patients	9 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Indeterminate	14 Number of patients	8 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the late follow up (LFU) (Day 42 to 49)

Population: The microbiological modified intent-to-treat (mMITT) analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=143 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=152 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Favorable	116 Number of patients	132 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Unfavorable	10 Number of patients	9 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Indeterminate	17 Number of patients	11 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=143 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=152 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Escherichia coli (n=84, 89)	77 Participants with favorable responses	86 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Klebsiella oxytoca (n=5, 5)	5 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Klebsiella pneumoniae (n=28,35)	22 Participants with favorable responses	32 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Pseudomonas aeruginosa (n=17, 20)	15 Participants with favorable responses	17 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Streptococcus anginosus grou (n=8, 7)	7 Participants with favorable responses	6 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Streptococcus mitis group (n=6, 5)	6 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Enterococcus faecalis (n=6, 6)	5 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Enterococcus faecium (n=4, 7)	4 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=143 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=152 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Escherichia coli (n=84, 89)	70 Participants with favorable responses	84 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Klebsiella oxytoca (n=5, 5)	5 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Klebsiella pneumoniae (n=28,35)	23 Participants with favorable responses	31 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Pseudomonas aeruginosa (n=17, 20)	14 Participants with favorable responses	17 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Streptococcus anginosus group (n=8, 7)	7 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Streptococcus mitis group (n=6, 5)	6 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Enterococcus faecalis (n=6, 6)	6 Participants with favorable responses	4 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Enterococcus faecium (n=4, 7)	4 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—

SECONDARY outcome

Timeframe: At the late follow up (LFU) (Day 42 to 49)

Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=143 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=152 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Escherichia coli (n=84, 89)	70 Participants with favorable responses	82 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Klebsiella pneumoniae (n=28, 35)	22 Participants with favorable responses	31 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Pseudomonas aeruginosa (n=17, 20)	14 Participants with favorable responses	17 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Klebsiella oxytoca (n=5, 5)	4 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Enterococcus faecalis (n=6, 6)	4 Participants with favorable responses	4 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Enterococcus faecium (n=4, 7)	3 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Streptococcus anginosus group (n=8, 7)	7 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Streptococcus mitis group (n=6, 5)	6 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=99 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=113 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. Escherichia coli (n=69, 77)	68 Participants with favorable responses	75 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. Klebsiella oxytoca (n=5, 5)	5 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. Klebsiella pneumoniae (n=22, 29)	21 Participants with favorable responses	28 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set. Pseudomonas aeruginosa (n=14, 16)	14 Participants with favorable responses	14 Participants with favorable responses	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=99 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=113 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. Escherichia coli (n=69, 77)	64 Participants with favorable responses	74 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. Klebsiella oxytoca (n=5, 5)	5 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. Klebsiella pneumoniae (n=22, 29)	21 Participants with favorable responses	28 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set. Pseudomonas aeruginosa (n=14, 16)	13 Participants with favorable responses	14 Participants with favorable responses	—	—	—	—

SECONDARY outcome

Timeframe: At the late follow up (LFU) (Day 42 to 49)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=99 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=113 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. Escherichia coli (n=69, 77)	63 Participants with favorable responses	72 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. Klebsiella oxytoca (n=5, 5)	4 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. Klebsiella pneumoniae (n=22, 29)	21 Participants with favorable responses	27 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set. Pseudomonas aeruginosa (n=14, 16)	13 Participants with favorable responses	14 Participants with favorable responses	—	—	—	—

SECONDARY outcome

Timeframe: At the end of treatment (EOT) (within 24 hours after last IV dose)

Population: Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=100 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=119 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Escherichia coli (n=70, 80)	69 Participants with favorable responses	78 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Klebsiella oxytoca (n=5, 5)	5 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Klebsiella pneumoniae (n=22, 30)	21 Participants with favorable responses	29 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Pseudomonas aeruginosa (n=14, 18)	14 Participants with favorable responses	16 Participants with favorable responses	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=100 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=119 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable(ME) Analysis Set. Escherichia coli (n=70, 80)	65 Participants with favorable responses	77 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable(ME) Analysis Set. Klebsiella oxytoca (n=5, 5)	5 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable(ME) Analysis Set. Klebsiella pneumoniae (n=22, 30)	21 Participants with favorable responses	29 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable(ME) Analysis Set. Pseudomonas aeruginosa (n=14, 18)	13 Participants with favorable responses	16 Participants with favorable responses	—	—	—	—

SECONDARY outcome

Timeframe: At the late follow up (LFU) (Day 42 to 49)

Population: Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=100 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=119 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Escherichia coli (n=70, 80)	64 Participants with favorable responses	75 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Klebsiella oxytoca (n=5, 5)	4 Participants with favorable responses	5 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Klebsiella pneumoniae (n=22, 30)	21 Participants with favorable responses	28 Participants with favorable responses	—	—	—	—
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set. Pseudomonas aeruginosa (n=14, 18)	13 Participants with favorable responses	16 Participants with favorable responses	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: The microbiological modified intent-to-treat (mMITT) analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

The microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=29 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=29 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Favorable	24 Number of patients	27 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Unfavorable	1 Number of patients	1 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set. Indeterminate	4 Number of patients	1 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

The microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=23 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=24 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiologically Evaluable (ME) Analysis Set. Favorable	22 Number of patients	23 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiologically Evaluable (ME) Analysis Set. Unfavorable	1 Number of patients	1 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At the test of cure (TOC) (Day 28 to 35)

Population: Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

The microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=23 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=26 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Extended Microbiologically Evaluable (ME) Analysis Set. Favorable	22 Number of patients	25 Number of patients	—	—	—	—
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Extended Microbiologically Evaluable (ME) Analysis Set. Unfavorable	1 Number of patients	1 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: while on study therapy (from Day 1 to Day 14)

Population: Clinically evaluable (CE) with fever, defined as \>38ºC at study entry. No participants were censored at the time of last observation.

Time to first defervescence was calculated for patients with a fever (\>38ºC) at baseline. Defervescence (≤37.8ºC) was defined as the absence of fever based on the highest temperature recorded on each study day. Time to first defervescence while on IV study therapy in the CE analysis set at TOC for patients who had fever at study entry is defined as time (in days) from the first dose of IV study therapy to first absence of fever.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=17 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=26 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Time to First Defervescence in the Clinically Evaluable (CE) Analysis Set for Patients Who Have Fever at Study Entry.	1 Days Interval 1.0 to 5.0	1.5 Days Interval 1.0 to 4.0	—	—	—	—

SECONDARY outcome

Timeframe: while on study therapy (from Day 1 to Day 14)

Population: microbiological modified intent-to-treat (mMITT) with fever, defined as \>38ºC at study entry. No participants were censored at the time of last observation.

Time to first defervescence was calculated for patients with a fever (\>38ºC) at baseline. Defervescence (≤37.8ºC) was defined as the absence of fever based on the highest temperature recorded on each study day. Time to first defervescence while on IV study therapy in the CE analysis set at TOC for patients who had fever at study entry is defined as time (in days) from the first dose of IV study therapy to first absence of fever.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=16 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=26 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
The Time to First Defervescence in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set for Patients Who Have Fever at Study Entry.	1 Days Interval 1.0 to 5.0	2 Days Interval 1.0 to 4.0	—	—	—	—

SECONDARY outcome

Timeframe: study duration (from screening to Day 49 LFU visit)

Population: Safety analysis set: all patients who received at least 1 dose of IP

Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42).

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=215 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=217 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality. Any AE	82 Number of patients	83 Number of patients	—	—	—	—
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality. Any SAE	9 Number of patients	11 Number of patients	—	—	—	—
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality. Any AE leading to discontinuation of IP	7 Number of patients	3 Number of patients	—	—	—	—
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality. Any AE of severe intensity	5 Number of patients	5 Number of patients	—	—	—	—
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality. Total number of deaths	2 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality. Deaths due to disease progression	2 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality. Any AE with outcome=death	0 Number of patients	1 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: study duration (from screening to Day 49 LFU visit)

Population: Safety analysis set: all patients who received at least 1 dose of IP

Duration of exposure is calculated as the difference between the last study therapy date and the first study therapy date converted to days plus 1 day. Actual calculated duration could be shorter or longer than a full day.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=215 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=217 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
Safety and Tolerability by Incidence: Extent of Exposure. 1 - 2 days	10 Number of patients	5 Number of patients	—	—	—	—
Safety and Tolerability by Incidence: Extent of Exposure. 3 - 4 days	6 Number of patients	5 Number of patients	—	—	—	—
Safety and Tolerability by Incidence: Extent of Exposure. 5 -10 days	175 Number of patients	181 Number of patients	—	—	—	—
Safety and Tolerability by Incidence: Extent of Exposure. 11 - 14 days	24 Number of patients	26 Number of patients	—	—	—	—
Safety and Tolerability by Incidence: Extent of Exposure. >14 days	0 Number of patients	0 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: study duration (from screening to Day 49 LFU visit)

Population: Safety analysis set: all patients who received at least 1 dose of IP

Potentially clinically significant (PCS) post Baseline hematology values up to LFU (Safety analysis set)

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=215 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=217 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Platelet count: PCS (Low)	1 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Platelet count: PCS (High)	5 Number of patients	4 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Red blood cell count: PCS (Low)	7 Number of patients	13 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Red blood cell count: PCS (High)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. White blood cell: PCS (Low)	1 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. White blood cell: PCS (High)	4 Number of patients	5 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Hemoglobin: PCS (Low)	7 Number of patients	14 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Hemoglobin: PCS (High)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Lymphocytes: PCS (Low)	1 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Lymphocytes: PCS (High)	0 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Neutrophils: PCS (Low)	4 Number of patients	2 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Neutrophils: PCS (High)	9 Number of patients	8 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Eosinophils: PCS (High)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Monocytes: PCS (High)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Basophils: PCS (High)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Direct Coombs test:- at Baseline, + post-Baseline	15 Number of patients	2 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Hematocrit (ratio): PCS (Low)	5 Number of patients	8 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Hematology. Hematocrit (ratio): PCS (High)	0 Number of patients	0 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: study duration (from screening to Day 49 LFU visit)

Population: Safety analysis set: all patients who received at least 1 dose of IP

Potentially clinically significant (PCS) post Baseline clinical chemistry values up to LFU (Safety analysis set)

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=215 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=217 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Alanine aminotransferase (μkat/L): PCS (High)	3 Number of patients	8 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Alkaline phosphatase (μkat/L): PCS (Low)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Alkaline phosphatase (μkat/L): PCS (High)	2 Number of patients	3 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Aspartate aminotransferase (μkat/L): PCS (High)	4 Number of patients	4 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Bicarbonate (mmol/L) PCS (Low)	1 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Bicarbonate (mmol/L): PCS (High)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Creatinine (μmol/L): PCS (High)	0 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Glucose (non-fasting) (mmol/L): PCS (Low)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Glucose (non-fasting) (mmol/L): PCS (High)	1 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Gamma-glutamyl transferase (μkat/L):PCS (High)	2 Number of patients	4 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Inorganic phosphorus (mmol/L): PCS (Low)	3 Number of patients	7 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Inorganic phosphorus (mmol/L): PCS (High)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Potassium (mmol/L): PCS (Low)	9 Number of patients	5 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Potassium (mmol/L): PCS (High)	3 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Total bilirubin (μmol/L): PCS (High)	0 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry. Direct bilirubin (μmol/L): PCS (High)	1 Number of patients	1 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: EOT visit/any observation on treatment

Population: Safety analysis set: all patients who received at least 1 dose of IP

Shifts in ECG interpretation and changes in QT, QTcB, and QTcF intervals , from baseline to post baseline.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=215 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=217 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) 30-90 minutes after	Avibactam(2) 30-90 minutes after	Ceftazidime(3) 300-360 minutes after	Avibactam(3) 300-360 minutes after
Safety and Tolerability:ECG , QTcB and QTcF Intervals Normal to Abnormal: EOT	17 Number of patients	14 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Normal to Abnormal: Anytime up to EOT	34 Number of patients	30 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Reaching a value in QT: ≥450 (ms)	9 Number of patients	10 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Reaching a value in QT: ≥480 (ms)	2 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Reaching a value in QT: ≥500 (ms)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals QT: ≥500 and increase from Baseline ≥60(ms)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Increase in QT: ≥30 (ms)	115 Number of patients	114 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Increase in QT: ≥60 (ms)	50 Number of patients	44 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Decrease in QT: ≥30 (ms)	24 Number of patients	24 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Decrease in QT: ≥60 (ms)	12 Number of patients	4 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Reaching a value in QTcB: ≥450(ms)	57 Number of patients	63 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Reaching a value in QTcB: ≥480(ms)	13 Number of patients	8 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Reaching a value in QTcB: ≥500 (ms)	4 Number of patients	2 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals QTcB: ≥500 and increase from Baseline ≥60(ms)	2 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Increase in QTcB: ≥30 (ms)	21 Number of patients	27 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Increase in QTcB: ≥60 (ms)	2 Number of patients	1 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Decrease in QTcB: ≥30 (ms)	42 Number of patients	26 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Decrease in QTcB: ≥60 (ms)	6 Number of patients	4 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Reaching a value in QTcF: ≥450 (ms)	19 Number of patients	18 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Reaching a value in QTcF: ≥480 (ms)	4 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Reaching a value in QTcF: ≥500 (ms)	1 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals QTcF: ≥500 and increase from Baseline ≥60 (ms)	0 Number of patients	0 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Increase in QTcF: ≥30 (ms)	42 Number of patients	41 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Increase in QTcF: ≥60 (ms)	4 Number of patients	3 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Decrease QTcF: ≥30 (ms)	21 Number of patients	19 Number of patients	—	—	—	—
Safety and Tolerability:ECG , QTcB and QTcF Intervals Decrease QTcF: ≥60 (ms)	7 Number of patients	1 Number of patients	—	—	—	—

SECONDARY outcome

Timeframe: At Day 3: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug.

Population: PK analysis set

Blood samples were taken from all patients on Day 3 for the pharmacokinetic evaluation of ceftazidime and avibactam plasma concentrations

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam Plus Metronidazole n=195 Participants Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion	Meropenem n=195 Participants Meropenem powder for solution for infusion 1000mg	Ceftazidime(2) n=193 Participants 30-90 minutes after	Avibactam(2) n=193 Participants 30-90 minutes after	Ceftazidime(3) n=192 Participants 300-360 minutes after	Avibactam(3) n=192 Participants 300-360 minutes after
Plasma Concentrations for Ceftazidime and Avibactam	60300.4 ng/mL Interval 1390.0 to 1880000.0	10126.9 ng/mL Interval 197.0 to 435000.0	46473.9 ng/mL Interval 2080.0 to 210000.0	7289.3 ng/mL Interval 229.0 to 36300.0	9555.0 ng/mL Interval 1740.0 to 222000.0	1207.2 ng/mL Interval 227.0 to 36300.0

Adverse Events

CAZ-AVI Plus Metronidazole

Serious events: 9 serious events

Other events: 44 other events

Deaths: 0 deaths

Meropenem

Serious events: 11 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	CAZ-AVI Plus Metronidazole n=215 participants at risk	Meropenem n=217 participants at risk Meropenem powder for solution for infusion 1000mg
Gastrointestinal disorders Constipation	2.3% 5/215 • Number of events 5 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.	1.4% 3/217 • Number of events 4 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
Gastrointestinal disorders Diarrhoea	6.0% 13/215 • Number of events 14 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.	7.4% 16/217 • Number of events 20 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
Gastrointestinal disorders Nausea	8.4% 18/215 • Number of events 25 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.	1.8% 4/217 • Number of events 4 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
Gastrointestinal disorders Vomiting	2.3% 5/215 • Number of events 8 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.	1.8% 4/217 • Number of events 5 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
General disorders Pyrexia	4.2% 9/215 • Number of events 12 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.	5.5% 12/217 • Number of events 21 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/215 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.	2.8% 6/217 • Number of events 6 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
Nervous system disorders Headache	1.4% 3/215 • Number of events 3 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.	2.3% 5/217 • Number of events 5 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
Respiratory, thoracic and mediastinal disorders Cough	1.4% 3/215 • Number of events 3 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.	3.7% 8/217 • Number of events 8 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
Respiratory, thoracic and mediastinal disorders Productive cough	2.3% 5/215 • Number of events 5 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.	2.8% 6/217 • Number of events 6 • Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary. AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.

Additional Information

David Wilson, Statistical Team Leader - Infection

AstraZeneca

Phone: +44 1625 517830

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees not to use such Confidential study information and not to disclose them to any other third parties, except that the undersigned shall not be prevented from using or disclosing information: (a) which by written records was previously known; (b) which is now public knowledge, (c) which is lawfully obtained by the undersigned from sources who have a lawful right to disclose such information.
Publication restrictions are in place

Restriction type: OTHER