Trial Outcomes & Findings for Ceftazidime-Avibactam for the Treatment of Infections Due to Ceftazidime Resistant Pathogens (NCT NCT01644643)

Last Updated: 2017-09-29

Results Overview

Proportion of patients with clinical cure at the TOC visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

345 participants

Primary outcome timeframe

6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Results posted on

2017-09-29

Participant Flow

A total of 333 patients were randomized in 53 centers in 16 countries: 306 patients had complicated urinary tract infection (cUTI) and 27 patients had complicated intra-abdominal infection (cIAI). The first patient was randomized on 07JAN2013 and the last patient was randomized on 29AUG2014. One patient in CAZ-AVI arm didn't receive study drug.

Participant milestones

Participant milestones
Measure	cIAI:Best Available Therapy cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI cUTI: CAZ-AVI
Overall Study STARTED	15	12	153	153
Overall Study COMPLETED	13	12	148	143
Overall Study NOT COMPLETED	2	0	5	10

Reasons for withdrawal

Reasons for withdrawal
Measure	cIAI:Best Available Therapy cIAI: Best Available Therapy Determinated by Investigator	cUTI:Best Available Therapy cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI cUTI: CAZ-AVI
Overall Study Death	1	3	3
Overall Study Lost to Follow-up	0	0	4
Overall Study Withdrawal by Subject	1	2	1
Overall Study Other Eligibility criteria	0	0	2

Baseline Characteristics

Ceftazidime-Avibactam for the Treatment of Infections Due to Ceftazidime Resistant Pathogens

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI: CAZ-AVI	Total n=302 Participants Total of all reporting groups
Age, Continuous	68.4 Years STANDARD_DEVIATION 11.12 • n=5 Participants	49.9 Years STANDARD_DEVIATION 16.14 • n=7 Participants	61.3 Years STANDARD_DEVIATION 15.33 • n=5 Participants	64.3 Years STANDARD_DEVIATION 14.64 • n=4 Participants	62.6 Years STANDARD_DEVIATION 15.12 • n=21 Participants
Age, Customized 18-45 Years	0 Participants n=5 Participants	3 Participants n=7 Participants	21 Participants n=5 Participants	19 Participants n=4 Participants	43 Participants n=21 Participants
Age, Customized 46-64 Years	3 Participants n=5 Participants	5 Participants n=7 Participants	49 Participants n=5 Participants	41 Participants n=4 Participants	98 Participants n=21 Participants
Age, Customized 65-74 Years	4 Participants n=5 Participants	2 Participants n=7 Participants	40 Participants n=5 Participants	46 Participants n=4 Participants	92 Participants n=21 Participants
Age, Customized 75-90 Years	4 Participants n=5 Participants	0 Participants n=7 Participants	27 Participants n=5 Participants	38 Participants n=4 Participants	69 Participants n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	63 Participants n=5 Participants	64 Participants n=4 Participants	137 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	4 Participants n=7 Participants	74 Participants n=5 Participants	80 Participants n=4 Participants	165 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Black Or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	8 Participants n=21 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants	9 Participants n=7 Participants	131 Participants n=5 Participants	136 Participants n=4 Participants	287 Participants n=21 Participants

PRIMARY outcome

Timeframe: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Response at Test of Cure (TOC) in Microbiological Modified Intent-to-treat (mMITT) Analysis Set Clinical cure	6 Participant Interval 27.0 to 80.0	8 Participant Interval 86.3 to 95.4	129 Participant Interval 89.3 to 97.2	132 Participant	—	—
Clinical Response at Test of Cure (TOC) in Microbiological Modified Intent-to-treat (mMITT) Analysis Set Clinical failure	0 Participant	0 Participant	2 Participant	2 Participant	—	—
Clinical Response at Test of Cure (TOC) in Microbiological Modified Intent-to-treat (mMITT) Analysis Set Indeterminate	5 Participant	2 Participant	6 Participant	10 Participant	—	—

SECONDARY outcome

Timeframe: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

Proportion of patients with clinical cure at the EOT visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Response at End of Treatment (EOT) in mMITT Analysis Set. Clinical failure	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Clinical Response at End of Treatment (EOT) in mMITT Analysis Set. Clinical cure	6 Participant	9 Participant	136 Participant	142 Participant	—	—
Clinical Response at End of Treatment (EOT) in mMITT Analysis Set. Indeterminate	5 Participant	1 Participant	1 Participant	2 Participant	—	—

SECONDARY outcome

Timeframe: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Population: Microbiological modified intent to treat

Proportion of patients with clinical cure at the FU1 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Response at Follow-up 1 (FU1) in mMITT Analysis Set Clinical cure	6 Participant	8 Participant	121 Participant	127 Participant	—	—
Clinical Response at Follow-up 1 (FU1) in mMITT Analysis Set Clinical failure	0 Participant	0 Participant	8 Participant	5 Participant	—	—
Clinical Response at Follow-up 1 (FU1) in mMITT Analysis Set Indeterminate	5 Participant	2 Participant	8 Participant	12 Participant	—	—

SECONDARY outcome

Timeframe: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Population: Microbiological modified intent to treat

Proportion of patients with clinical cure at the FU2 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Response at Follow-up 2 (FU2) in mMITT Analysis Set Clinical cure	—	—	118 Participant	123 Participant	—	—
Clinical Response at Follow-up 2 (FU2) in mMITT Analysis Set Clinical failure	—	—	13 Participant	11 Participant	—	—
Clinical Response at Follow-up 2 (FU2) in mMITT Analysis Set Indeterminate	—	—	6 Participant	10 Participant	—	—

SECONDARY outcome

Timeframe: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Extended Microbiological Evaluable at EOT analysis set.

Proportion of patients with clinical cure at the EOT visit in the EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=9 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=127 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=134 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Response at EOT in Extended Microbiologically Evaluable (EME) at EOT Analysis Set. Clinical cure	5 Participant	9 Participant	127 Participant	134 Participant	—	—
Clinical Response at EOT in Extended Microbiologically Evaluable (EME) at EOT Analysis Set. Clinical failure	0 Participant	0 Participant	0 Participant	0 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Population: Extended Microbiological Evaluable at TOC analysis set.

Proportion of patients with clinical cure at the TOC visit in the EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=8 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=122 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=128 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Response at TOC in EME at TOC Analysis Set. Clinical cure	5 Participant	8 Participant	120 Participant	126 Participant	—	—
Clinical Response at TOC in EME at TOC Analysis Set. Clinical failure	0 Participant	0 Participant	2 Participant	2 Participant	—	—

SECONDARY outcome

Timeframe: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Population: Extended Microbiological Evaluable at FU1 analysis set.

Proportion of patients with clinical cure at the FU1 visit in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=7 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=118 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=124 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Response at FU1 in EME at FU1 Analysis Set. Clinical cure	5 Participant	7 Participant	110 Participant	120 Participant	—	—
Clinical Response at FU1 in EME at FU1 Analysis Set. Clinical failure	0 Participant	0 Participant	8 Participant	4 Participant	—	—

SECONDARY outcome

Timeframe: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Population: Extended Microbiological Evaluable at FU2 analysis set.

Proportion of patients with clinical cure at the FU2 visit in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=114 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=116 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Response at FU2 in EME at FU2 Analysis Set Clinical cure	—	—	102 Participant	106 Participant	—	—
Clinical Response at FU2 in EME at FU2 Analysis Set Clinical failure	—	—	12 Participant	10 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

Proportion of patients with clinical cure at TOC visit by baseline pathogen (\>=10% of frequency in the combined cIAI and cUTI patients) in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Cure at TOC by Baseline Gram-negative Pathogen in mMITT Analysis Set K. pneumoniae - Clinical cure (n=3, 5, 65, 55)	2 Participant	3 Participant	61 Participant	54 Participant	—	—
Clinical Cure at TOC by Baseline Gram-negative Pathogen in mMITT Analysis Set E. coli - Clinical cure (n=6, 4, 57, 59)	2 Participant	3 Participant	54 Participant	53 Participant	—	—
Clinical Cure at TOC by Baseline Gram-negative Pathogen in mMITT Analysis Set P. aeruginosa - clinical cure (n=1, 1, 5, 14)	1 Participant	1 Participant	5 Participant	12 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Population: Extended microbiologically evaluable at TOC

Proportion of patients with clinical cure at TOC visit by baseline Gram-negative pathogen (\>=10% of frequency in the combined cIAI and cUTI patients) in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=8 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=124 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=131 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Cure at TOC by Baseline Gram-negative Pathogen in EME at TOC Analysis Set E. coli - Clinical cure (n=2, 3, 48, 52)	2 Participant	3 Participant	47 Participant	51 Participant	—	—
Clinical Cure at TOC by Baseline Gram-negative Pathogen in EME at TOC Analysis Set K. pneumoniae - Clinical cure (n=2, 3, 59, 53)	2 Participant	3 Participant	59 Participant	53 Participant	—	—
Clinical Cure at TOC by Baseline Gram-negative Pathogen in EME at TOC Analysis Set P. aeruginosa - Clinical cure (n=1, 1, 5, 12)	1 Participant	1 Participant	5 Participant	12 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

Proportion of patients with clinical cure at TOC visit by previously failed treatment class in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Imidazole Derivatives - Clin. cure (n=2,3,0,0)	1 Participant	3 Participant	0 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Antibiotics - Clin. cure (n=0,1,0,0)	0 Participant	1 Participant	0 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Other Aminoglycosides-Clin. cure (n=0,0,1,1)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Comb of Sulf/Trime inc Deriv-Clin. cure(n=0,0,2,0)	0 Participant	0 Participant	2 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)	1 Participant	3 Participant	0 Participant	2 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Cortico,Po. Comb W/Antibio.-Clin. cure(n=0,0,1,0)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set First-Gen. Cephalosporins-Clin. cure (n=0,0,2,0)	0 Participant	0 Participant	2 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Fluoroquinolones - Clin. cure (n=1,2,7,1)	0 Participant	2 Participant	7 Participant	1 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Glycopeptide Antibacterials-Clin. cure (n=1,0,0,0)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Other Antibacterials-Clin. cure (n=0,1,1,0)	0 Participant	1 Participant	1 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Third-Gen.Cephalosporins -Clin. cure(n=2,4,3,2)	2 Participant	4 Participant	3 Participant	2 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set At least 1 failed - Clin. cure (n=4,7,12,7)	3 Participant	7 Participant	12 Participant	6 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Carbapenems - Clin. cure (n=1,0,1,2)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Other Antibio. F. Topic. Use-Clin. cure(n=0,0,1,0)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set Penici. With Ext. Spectrum-Clin. cure(n=0,1,0,0)	0 Participant	1 Participant	0 Participant	0 Participant	—	—

SECONDARY outcome

Timeframe: 28 hours after completion of last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Population: Extended microbiologically evaluable at EOT

Proportion of patients with clinical cure at EOT visit by previously failed treatment class in EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=9 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=127 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=134 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Other Aminoglycosides-Clin. cure (n=0,0,1,1)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Comb of Sulf/Trime inc Deriv-Clin. cure(n=0,0,2,0)	0 Participant	0 Participant	2 Participant	0 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set First-Gen. Cephalosporins-Clin. cure (n=0,0,2,0)	0 Participant	0 Participant	2 Participant	0 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Fluoroquinolones - Clin. cure (n=0,2,5,1)	0 Participant	2 Participant	5 Participant	1 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Imidazole Derivatives - Clin. cure (n=1,3,0,0)	1 Participant	3 Participant	0 Participant	0 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Other Antibacterials-Clin. cure (n=0,1,1,0)	0 Participant	1 Participant	1 Participant	0 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Other Antibio. F. Topic. Use-Clin. cure(n=0,0,1,0)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Penici. With Ext. Spectrum-Clin. cure(n=0,1,0,0)	0 Participant	1 Participant	0 Participant	0 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Third-Gen.Cephalosporins -Clin. cure(n=2,4,2,2)	2 Participant	4 Participant	2 Participant	2 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Antibiotics - Clin. cure (n=0,1,0,0)	0 Participant	1 Participant	0 Participant	0 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Carbapenems - Clin. cure (n=0,0,1,1)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)	1 Participant	3 Participant	0 Participant	2 Participant	—	—
Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set Cortico,Po. Comb W/Antibio.-Clin. cure(n=0,0,1,0)	0 Participant	0 Participant	1 Participant	0 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Extended microbiologically evaluable at TOC

Proportion of patients with clinical cure at TOC visit by previously failed treatment class in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=8 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=122 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=128 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Cortico,Po. Comb W/Antibio.-Clin. cure(n=0,0,1,0)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Other Antibio. F. Topic. Use-Clin. cure(n=0,0,1,0)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Antibiotics - Clin. cure (n=0,1,0,0)	0 Participant	1 Participant	0 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Carbapenems - Clin. cure (n=0,0,1,1)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Comb of Sulf/Trime inc Deriv-Clin. cure(n=0,0,2,0)	0 Participant	0 Participant	2 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)	1 Participant	3 Participant	0 Participant	2 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set First-Gen. Cephalosporins-Clin. cure (n=0,0,2,0)	0 Participant	0 Participant	2 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Fluoroquinolones - Clin. cure (n=0,2,5,1)	0 Participant	2 Participant	5 Participant	1 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Imidazole Derivatives - Clin. cure (n=1,3,0,0)	1 Participant	3 Participant	0 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Other Aminoglycosides-Clin. cure (n=0,0,0,1)	0 Participant	0 Participant	0 Participant	1 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Other Antibacterials-Clin. cure (n=0,1,1,0)	0 Participant	1 Participant	1 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Penici. With Ext. Spectrum-Clin. cure(n=0,1,0,0)	0 Participant	1 Participant	0 Participant	0 Participant	—	—
Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set Third-Gen.Cephalosporins -Clin. cure(n=2,4,2,2)	2 Participant	4 Participant	2 Participant	2 Participant	—	—

SECONDARY outcome

Timeframe: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Population: Extended microbiologically evaluable at FU1

Proportion of patients with clinical cure at FU1 visit by previously failed treatment class in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=7 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=118 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=124 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Other Antibacterials-Clin. cure (n=0,1,1,0)	0 Participant	1 Participant	1 Participant	0 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)	1 Participant	3 Participant	0 Participant	2 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Penici. With Ext. Spectrum-Clin. cure(n=0,1,0,0)	0 Participant	1 Participant	0 Participant	0 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Other Antibio. F. Topic. Use-Clin. cure(n=0,0,1,0)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Antibiotics - Clin. cure (n=0,1,0,0)	0 Participant	1 Participant	0 Participant	0 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Carbapenems - Clin. cure (n=0,0,1,1)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Comb of Sulf/Trime inc Deriv-Clin. cure(n=0,0,1,0)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Cortico,Po. Comb W/Antibio.-Clin. cure(n=0,0,1,0)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set First-Gen. Cephalosporins-Clin. cure (n=0,0,2,0)	0 Participant	0 Participant	2 Participant	0 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Fluoroquinolones - Clin. cure (n=0,2,5,1)	0 Participant	2 Participant	4 Participant	1 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Imidazole Derivatives - Clin. cure (n=1,3,0,0)	1 Participant	3 Participant	0 Participant	0 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Other Aminoglycosides-Clin. cure (n=0,0,0,1)	0 Participant	0 Participant	0 Participant	1 Participant	—	—
Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set Third-Gen.Cephalosporins -Clin. cure(n=2,4,1,2)	2 Participant	4 Participant	0 Participant	2 Participant	—	—

SECONDARY outcome

Timeframe: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Population: Extended microbiologically evaluable at FU2

Proportion of patients with clinical cure at FU2 visit by previously failed treatment class in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=114 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=116 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set First-Gen. Cephalosporins-Clin. cure (n=2,0)	—	—	2 Participant	0 Participant	—	—
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set Other Antibio. F. Topic. Use-Clin. cure(n=1,0)	—	—	1 Participant	0 Participant	—	—
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set Third-Gen.Cephalosporins -Clin. cure(n=1,1)	—	—	0 Participant	1 Participant	—	—
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set Carbapenems - Clin. cure (n=1,0)	—	—	0 Participant	0 Participant	—	—
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set Comb of Sulf/Trime inc Deriv-Clin. cure(n=1,0)	—	—	0 Participant	0 Participant	—	—
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=0,2)	—	—	0 Participant	2 Participant	—	—
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set Cortico,Po. Comb W/Antibio.-Clin. cure(n=1,0)	—	—	0 Participant	0 Participant	—	—
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set Fluoroquinolones - Clin. cure (n=5,0)	—	—	4 Participant	0 Participant	—	—
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set Other Aminoglycosides-Clin. cure (n=0,1)	—	—	0 Participant	1 Participant	—	—
Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set Other Antibacterials-Clin. cure (n=1,0)	—	—	0 Participant	0 Participant	—	—

SECONDARY outcome

Timeframe: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

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 cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel 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	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-patient Microbiological Response at EOT in mMITT Analysis Set Favorable	6 Participant	9 Participant	130 Participant	136 Participant	—	—
Per-patient Microbiological Response at EOT in mMITT Analysis Set Unfavorable	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Per-patient Microbiological Response at EOT in mMITT Analysis Set Indeterminate	5 Participant	1 Participant	6 Participant	7 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-patient Microbiological Response at TOC in mMITT Analysis Set Favorable	6 Participant	8 Participant	88 Participant	118 Participant	—	—
Per-patient Microbiological Response at TOC in mMITT Analysis Set Unfavorable	0 Participant	0 Participant	42 Participant	17 Participant	—	—
Per-patient Microbiological Response at TOC in mMITT Analysis Set Indeterminate	5 Participant	2 Participant	7 Participant	9 Participant	—	—

SECONDARY outcome

Timeframe: cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization

Population: Microbiological modified intent to treat

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-patient Microbiological Response at FU1 in mMITT Analysis Set Indeterminate	5 Participant	2 Participant	9 Participant	12 Participant	—	—
Per-patient Microbiological Response at FU1 in mMITT Analysis Set Favorable	6 Participant	8 Participant	78 Participant	103 Participant	—	—
Per-patient Microbiological Response at FU1 in mMITT Analysis Set Unfavorable	0 Participant	0 Participant	50 Participant	29 Participant	—	—

SECONDARY outcome

Timeframe: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Population: Microbiological modified intent to treat

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-patient Microbiological Response at FU2 in mMITT Analysis Set Favorable	—	—	73 Participant	99 Participant	—	—
Per-patient Microbiological Response at FU2 in mMITT Analysis Set Indeterminate	—	—	10 Participant	10 Participant	—	—
Per-patient Microbiological Response at FU2 in mMITT Analysis Set Unfavorable	—	—	54 Participant	35 Participant	—	—

SECONDARY outcome

Timeframe: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Extended microbiologically evaluable at EOT

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=9 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=127 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=134 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-patient Microbiological Response at EOT in EME at EOT Analysis Set Favorable	5 Participant	9 Participant	127 Participant	133 Participant	—	—
Per-patient Microbiological Response at EOT in EME at EOT Analysis Set Unfavorable	0 Participant	0 Participant	0 Participant	1 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Population: Extended microbiologically evaluable at TOC

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=8 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=124 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=131 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-patient Microbiological Response at TOC in EME at TOC Analysis Set Favorable	5 Participant	8 Participant	84 Participant	114 Participant	—	—
Per-patient Microbiological Response at TOC in EME at TOC Analysis Set Unfavorable	0 Participant	0 Participant	40 Participant	17 Participant	—	—

SECONDARY outcome

Timeframe: cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization

Population: Extended microbiologically evaluable at FU1

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=7 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=120 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=126 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-patient Microbiological Response at FU1 in EME at FU1 Analysis Set Favorable	5 Participant	7 Participant	75 Participant	98 Participant	—	—
Per-patient Microbiological Response at FU1 in EME at FU1 Analysis Set Unfavorable	0 Participant	0 Participant	45 Participant	28 Participant	—	—

SECONDARY outcome

Timeframe: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Population: Extended microbiologically evaluable at FU2

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=115 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=117 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-patient Microbiological Response at FU2 in EME at FU2 Analysis Set Favorable	—	—	68 Participant	85 Participant	—	—
Per-patient Microbiological Response at FU2 in EME at FU2 Analysis Set Unfavorable	—	—	47 Participant	32 Participant	—	—

SECONDARY outcome

Timeframe: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

Proportion of patients with a favorable per-pathogen microbiological response for pathogens (\>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10\^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set Kleb. pneumoniae - Favorable (n=3, 5, 65, 55)	2 Participant	4 Participant	61 Participant	52 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set Kleb. pneumoniae - Indeterminate (n=3, 5, 65, 55)	1 Participant	1 Participant	3 Participant	3 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set Pseudo. aeruginosa - Indeterminate (n=1, 1, 5, 14)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set Escherichia coli - Favorable (n=6, 4, 57, 59)	2 Participant	3 Participant	53 Participant	57 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set Escherichia coli - Unfavorable (n=6, 4, 57, 59)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set Escherichia coli - Indeterminate (n=6, 4, 57, 59)	4 Participant	1 Participant	4 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set Kleb. pneumoniae - Unfavorable (n=3, 5, 65, 55)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set Pseudo. aeruginosa - Favorable (n=1, 1, 5, 14)	1 Participant	1 Participant	5 Participant	14 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 14)	0 Participant	0 Participant	0 Participant	0 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set Escherichia coli - Favorable (n=6, 4, 57, 59)	2 Participant	3 Participant	38 Participant	52 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set Escherichia coli - Indeterminate (n=6, 4, 57, 59)	4 Participant	1 Participant	3 Participant	4 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set Pseudo. aeruginosa - Indeterminate (n=1, 1, 5, 14)	0 Participant	0 Participant	0 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set Escherichia coli - Unfavorable (n=6, 4, 57, 59)	0 Participant	0 Participant	16 Participant	3 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set Kleb. pneumoniae - Favorable (n=3, 5, 65, 55)	2 Participant	3 Participant	43 Participant	46 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set Kleb. pneumoniae - Unfavorable (n=3, 5, 65, 55)	0 Participant	0 Participant	19 Participant	8 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set Kleb. pneumoniae - Indeterminate (n=3, 5, 65, 55)	1 Participant	2 Participant	3 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set Pseudo. aeruginosa - Favorable (n=1, 1, 5, 14)	1 Participant	1 Participant	3 Participant	11 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 14)	0 Participant	0 Participant	2 Participant	2 Participant	—	—

SECONDARY outcome

Timeframe: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Population: Microbiological modified intent to treat

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set Kleb. pneumoniae - Unfavorable (n=3, 5, 65, 55)	0 Participant	0 Participant	23 Participant	10 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set Kleb. pneumoniae - Indeterminate (n=3, 5, 65, 55)	1 Participant	2 Participant	3 Participant	3 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set Escherichia coli - Favorable (n=6, 4, 57, 59)	2 Participant	3 Participant	33 Participant	45 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set Escherichia coli - Unfavorable (n=6, 4, 57, 59)	0 Participant	0 Participant	18 Participant	12 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set Escherichia coli - Indeterminate (n=6, 4, 57, 59)	4 Participant	1 Participant	6 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set Kleb. pneumoniae - Favorable (n=3, 5, 65, 55)	2 Participant	3 Participant	39 Participant	42 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set Pseudo. aeruginosa - Favorable (n=1, 1, 5, 14)	1 Participant	1 Participant	3 Participant	8 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 14)	0 Participant	0 Participant	2 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set Pseudo. aeruginosa - Indeterminate (n=1, 1, 5, 14)	0 Participant	0 Participant	0 Participant	4 Participant	—	—

SECONDARY outcome

Timeframe: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Population: Microbiological modified intent to treat

Proportion of patients with a favorable per-pathogen microbiological response for pathogens (\>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10\^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set Escherichia coli - Favorable (n=0, 0, 57, 59)	—	—	32 Participant	43 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set Escherichia coli - Unfavorable (n=0, 0, 57, 59)	—	—	19 Participant	14 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set Escherichia coli - Indeterminate (n=0, 0, 57, 59)	—	—	6 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set Kleb. pneumoniae - Favorable (n=0, 0, 65, 55)	—	—	35 Participant	39 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set Kleb. pneumoniae - Unfavorable (n=0, 0, 65, 55)	—	—	26 Participant	14 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set Kleb. pneumoniae - Indeterminate (n=0, 0, 65, 55)	—	—	4 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set Pseudo. aeruginosa - Favorable (n=0, 0, 5, 14)	—	—	2 Participant	10 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set Pseudo. aeruginosa - Unfavorable (n=0, 0, 5, 14)	—	—	3 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set Pseudo. aeruginosa - Indeterminate (n=0, 0, 5, 14)	—	—	0 Participant	2 Participant	—	—

SECONDARY outcome

Timeframe: 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Extended microbiologically evaluable at EOT

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=9 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=127 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=134 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set Kleb. pneumoniae - Unfavorable (n=2, 4, 60, 52)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set Escherichia coli - Favorable (n=2, 3, 51, 55)	2 Participant	3 Participant	51 Participant	55 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set Escherichia coli - Unfavorable (n=2, 3, 51, 55)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set Kleb. pneumoniae - Favorable (n=2, 4, 60, 52)	2 Participant	4 Participant	60 Participant	52 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set Pseudo. aeruginosa - Favorable (n=1, 1, 5, 14)	1 Participant	1 Participant	5 Participant	14 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 14)	0 Participant	0 Participant	0 Participant	0 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Extended microbiologically evaluable at TOC

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=8 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=124 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=131 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set Kleb. pneumoniae - Unfavorable (n=2, 3, 60, 53)	0 Participant	0 Participant	18 Participant	8 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set Escherichia coli - Favorable (n=2, 3, 49, 53)	2 Participant	3 Participant	34 Participant	50 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set Escherichia coli - Unfavorable (n=2, 3, 49, 53)	0 Participant	0 Participant	15 Participant	3 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set Kleb. pneumoniae - Favorable (n=2, 3, 60, 53)	2 Participant	3 Participant	42 Participant	45 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set Pseudo. aeruginosa - Favorable (n=1, 1, 5, 13)	1 Participant	1 Participant	3 Participant	11 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 13)	0 Participant	0 Participant	2 Participant	2 Participant	—	—

SECONDARY outcome

Timeframe: cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Population: Extended microbiologically evaluable at FU1

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=7 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=120 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=126 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set Escherichia coli - Favorable (n=2, 3, 46, 54)	2 Participant	3 Participant	30 Participant	43 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set Escherichia coli - Unfavorable (n=2, 3, 46, 54)	0 Participant	0 Participant	16 Participant	11 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set Kleb. pneumoniae - Favorable (n=2, 2, 59, 50)	2 Participant	2 Participant	38 Participant	40 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set Kleb. pneumoniae - Unfavorable (n=2, 2, 59, 50)	0 Participant	0 Participant	21 Participant	10 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set Pseudo. aeruginosa - Favorable (n=1, 1, 5, 10)	1 Participant	1 Participant	3 Participant	8 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 10)	0 Participant	0 Participant	2 Participant	2 Participant	—	—

SECONDARY outcome

Timeframe: At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Population: Extended microbiologically evaluable at FU2

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=115 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=117 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set Escherichia coli - Favorable (n=44, 50)	—	—	28 Participant	39 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set Escherichia coli - Unfavorable (n=44, 50)	—	—	16 Participant	11 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set Kleb. pneumoniae - Favorable (n= 56, 46)	—	—	33 Participant	32 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set Kleb. pneumoniae - Unfavorable (n=56, 46)	—	—	23 Participant	14 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set Pseudo. aeruginosa - Favorable (n=4, 11)	—	—	2 Participant	9 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set Pseudo. aeruginosa - Unfavorable (n=4, 11)	—	—	2 Participant	2 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set E. coli (MIC: 0.06) - Favorable (n=1, 0, 3, 2)	0 Participant	0 Participant	3 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set E. coli (MIC: <=0.008) - Favorable (n=0, 0, 1, 1)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set E. coli (MIC: 0.03) - Favorable (n=0, 0, 0, 2)	0 Participant	0 Participant	0 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set E. coli (MIC: 0.12) - Favorable (n=4, 2, 20, 20)	2 Participant	1 Participant	12 Participant	16 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set E. coli (MIC: 0.25) - Favorable (n=0, 0, 15, 16)	0 Participant	0 Participant	10 Participant	15 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set P. aeruginosa (MIC: 2) - Favorable (n=1, 0, 0, 1)	1 Participant	0 Participant	0 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set P. aeruginosa (MIC: 4) - Favorable (n=0, 0, 3, 2)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set P. aeruginosa (MIC: 8) - Favorable (n=0, 0, 0, 2)	0 Participant	0 Participant	0 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set E. coli (MIC: 0.5) - Favorable (n=0, 1, 8, 11)	0 Participant	1 Participant	5 Participant	10 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set E. coli (MIC: 1) - Favorable (n=0, 0, 2, 2)	0 Participant	0 Participant	1 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set E. coli (MIC: 2) - Favorable (n=0, 0, 2, 1)	0 Participant	0 Participant	2 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set E. coli (MIC: 8) - Favorable (n=0, 0, 2, 4)	0 Participant	0 Participant	2 Participant	4 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set K. pneumoniae (MIC: 0.06) - Favorable (n=0,0,2,0)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set K. pneumoniae (MIC: 0.12) - Favorable (n=0,1,8,5)	0 Participant	0 Participant	6 Participant	4 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set K. pneumoniae (MIC: 0.25) - Favorable (n=0,3,12,6)	0 Participant	2 Participant	7 Participant	5 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set K. pneumoniae (MIC: 0.5) - Favorable (n=2,0,24,22)	1 Participant	0 Participant	16 Participant	19 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set K. pneumoniae (MIC: 1) - Favorable (n=0,0,16,18)	0 Participant	0 Participant	11 Participant	16 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set K. pneumoniae (MIC: 2) - Favorable (n=1, 1, 1, 2)	1 Participant	1 Participant	1 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set K. pneumoniae (MIC: 4) - Favorable (n=0, 0, 1, 1)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set K. pneumoniae (MIC: 32) - Favorable (n=0, 0, 1, 0)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set K. pneumoniae (MIC: >32) - Favorable (n=0,0,0,1)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set P. aeruginosa (MIC: 16) - Favorable (n=0, 1, 0, 1)	0 Participant	1 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set P. aeruginosa (MIC: 32) - Favorable (n=0, 0, 1, 3)	0 Participant	0 Participant	1 Participant	3 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set P. aeruginosa (MIC: >32) - Favorable (n=0,0,1,5)	0 Participant	0 Participant	1 Participant	4 Participant	—	—

SECONDARY outcome

Timeframe: 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Extended microbiologically evaluable at TOC

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=8 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=124 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=131 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set E. coli (MIC: <=0.008) - Favorable (n=0, 0, 1, 1)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set E. coli (MIC: 0.03) - Favorable (n=0, 0, 0, 2)	0 Participant	0 Participant	0 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set E. coli (MIC: 0.06) - Favorable (n=0, 0, 3, 1)	0 Participant	0 Participant	3 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set E. coli (MIC: 0.12) - Favorable (n=2, 1, 18, 18)	2 Participant	1 Participant	10 Participant	16 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set E. coli (MIC: 0.25) - Favorable (n=0, 0, 13, 15)	0 Participant	0 Participant	9 Participant	15 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set E. coli (MIC: 0.5) - Favorable (n=0, 1, 6, 9)	0 Participant	1 Participant	4 Participant	9 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set E. coli (MIC: 1) - Favorable (n=0, 0, 2, 2)	0 Participant	0 Participant	1 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set E. coli (MIC: 2) - Favorable (n=0, 0, 2, 1)	0 Participant	0 Participant	2 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set E. coli (MIC: 8) - Favorable (n=0, 0, 2, 4)	0 Participant	0 Participant	2 Participant	4 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set K. pneumoniae (MIC: 0.06) - Favorable (n=0,0,1,0)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set K. pneumoniae (MIC: 0.12) - Favorable (n=0,0,8,5)	0 Participant	0 Participant	6 Participant	4 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set K. pneumoniae (MIC: 0.25) - Favorable (n=0,2,11,6)	0 Participant	2 Participant	7 Participant	5 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set K. pneumoniae (MIC: 0.5) - Favorable (n=1,0,23,21)	1 Participant	0 Participant	16 Participant	19 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set K. pneumoniae (MIC: 1) - Favorable (n=0,0,15,17)	0 Participant	0 Participant	11 Participant	15 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set K. pneumoniae (MIC: 2) - Favorable (n=1, 1, 1, 2)	1 Participant	1 Participant	1 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set K. pneumoniae (MIC: 4) - Favorable (n=0, 0, 1, 1)	0 Participant	0 Participant	1 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set K. pneumoniae (MIC: >32) - Favorable (n=0,0,0,1)	0 Participant	0 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set P. aeruginosa (MIC: 2) - Favorable (n=1, 0, 0, 1)	1 Participant	0 Participant	0 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set P. aeruginosa (MIC: 4) - Favorable (n=0, 0, 3, 2)	0 Participant	0 Participant	1 Participant	1 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set P. aeruginosa (MIC: 8) - Favorable (n=0, 0, 0, 2)	0 Participant	0 Participant	0 Participant	2 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set P. aeruginosa (MIC: 16) - Favorable (n=0, 1, 0, 1)	0 Participant	1 Participant	0 Participant	0 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set P. aeruginosa (MIC: 32) - Favorable (n=0, 0, 1, 3)	0 Participant	0 Participant	1 Participant	3 Participant	—	—
Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set P. aeruginosa (MIC: >32) - Favorable (n=0,0,1,4)	0 Participant	0 Participant	1 Participant	4 Participant	—	—

SECONDARY outcome

Timeframe: From first infusion to last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Population: Microbiological modified intent to treat

Proportion of patients in the mMITT analysis set for whom the assigned study treatment was changed, discontinued, or interrupted. Creatinine clearance (CrCl)

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set Treatment Change	1 Participant	0 Participant	8 Participant	11 Participant	—	—
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set Treatment Change - Crcl change	1 Participant	0 Participant	5 Participant	10 Participant	—	—
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set Treatment Change - Other	0 Participant	0 Participant	3 Participant	1 Participant	—	—
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set Treatment discontinuation	4 Participant	0 Participant	3 Participant	1 Participant	—	—
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set Treatment discontinuation - AE	1 Participant	0 Participant	1 Participant	1 Participant	—	—
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set Treatment discontinuation - Other	3 Participant	0 Participant	2 Participant	0 Participant	—	—
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set Treatment interrupted	0 Participant	0 Participant	0 Participant	1 Participant	—	—
The Reason for Treatment Change/Discontinuation in mMITT Analysis Set Treatment interrupted - Change of infusion site	0 Participant	0 Participant	0 Participant	1 Participant	—	—

SECONDARY outcome

Timeframe: From first infusion to Day 28

Population: Microbiological modified intent to treat

Proportion of patients with Day 28 all-cause mortality in mMITT analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=11 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=10 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=137 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=144 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
The 28 Days All Cause Mortality Rate in mMITT Analysis Set All cause mortality	1 Participant	0 Participant	3 Participant	3 Participant	—	—
The 28 Days All Cause Mortality Rate in mMITT Analysis Set Deaths due to disease progression	0 Participant	0 Participant	0 Participant	0 Participant	—	—
The 28 Days All Cause Mortality Rate in mMITT Analysis Set Number of patients with any AE with outcome=death	1 Participant	0 Participant	3 Participant	3 Participant	—	—

SECONDARY outcome

Timeframe: From first infusion to Day 28

Population: Extended microbiologically evaluable at TOC

Proportion of patients with Day 28 all-cause mortality in EME at TOC analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=5 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=8 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=124 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=131 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) 300-360 mins after dose	AVI (3) 300-360 mins after dose
The 28 Days All Cause Mortality Rate in EME at TOC Analysis Set All cause mortality	0 Participant	0 Participant	1 Participant	1 Participant	—	—
The 28 Days All Cause Mortality Rate in EME at TOC Analysis Set Deaths due to disease progression	0 Participant	0 Participant	0 Participant	0 Participant	—	—
The 28 Days All Cause Mortality Rate in EME at TOC Analysis Set Number of patients with any AE withoutcome=death	0 Participant	0 Participant	1 Participant	1 Participant	—	—

SECONDARY outcome

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

Population: PK Analysis set

Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=12 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=12 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=12 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=12 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) n=12 Participants 300-360 mins after dose	AVI (3) n=12 Participants 300-360 mins after dose
Plasma Concentrations for Ceftazidime and Avibactam - cIAI in PK Analysis Set	23880.3 NG/ML Interval 2700.0 to 80900.0	3061.3 NG/ML Interval 286.0 to 13200.0	39465.3 NG/ML Interval 2620.0 to 85500.0	6304.1 NG/ML Interval 285.0 to 15500.0	14904.8 NG/ML Interval 2500.0 to 58100.0	1769.3 NG/ML Interval 277.0 to 7900.0

SECONDARY outcome

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

Population: PK Analysis set

Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.

Outcome measures

Outcome measures
Measure	cIAI:Best Available Therapy n=145 Participants cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI + Metronidazole n=147 Participants cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy n=141 Participants cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI n=147 Participants cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	CAZ (3) n=146 Participants 300-360 mins after dose	AVI (3) n=146 Participants 300-360 mins after dose
Plasma Concentrations for Ceftazidime and Avibactam - cUTI in PK Analysis Set	74260.2 NG/ML Interval 5970.0 to 1640000.0	10103.8 NG/ML Interval 504.0 to 376000.0	56905.9 NG/ML Interval 14700.0 to 1910000.0	8141.2 NG/ML Interval 773.0 to 405000.0	21442.0 NG/ML Interval 2490.0 to 1600000.0	2425.0 NG/ML Interval 315.0 to 431000.0

Adverse Events

cIAI:Best Available Therapy

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

cIAI:CAZ-AVI + Metronidazole

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

cUTI:Best Available Therapy

Serious events: 5 serious events

Other events: 36 other events

Deaths: 0 deaths

cUTI:CAZ-AVI

Serious events: 7 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Yunxia Lu

AstraZeneca-PPD

Phone: 910-558-4197

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