Trial Outcomes & Findings for Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE) (NCT NCT02655419)

Results Overview

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

4 hr Post dose on Day 4

Results posted on

2020-04-02

Participant Flow

The study was conducted at 11 centers in 3 countries from 19-May-2016 to 26-Oct-2017.

Participant milestones

Participant milestones
Measure	Aztreonam-Avibactam(ATM-AVI)+Metronidazole:Low AVI Dose Cohort Participants with normal renal function or mild renal impairment (Creatinine clearance \[CrCl\] greater than\[\>\] 50 milliliter per minute \[mL/min\]), received intravenous (IV) infusion of 500 milligram (mg) ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Study STARTED	17	23
Overall Study Treated	16	18
Overall Study COMPLETED	12	16
Overall Study NOT COMPLETED	5	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Aztreonam-Avibactam(ATM-AVI)+Metronidazole:Low AVI Dose Cohort Participants with normal renal function or mild renal impairment (Creatinine clearance \[CrCl\] greater than\[\>\] 50 milliliter per minute \[mL/min\]), received intravenous (IV) infusion of 500 milligram (mg) ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Study Enrolled but not treated	1	5
Overall Study Withdrawal by Subject	4	1
Overall Study Other	0	1

Baseline Characteristics

Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=18 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	Total n=34 Participants Total of all reporting groups
Age, Continuous	49.00 years STANDARD_DEVIATION 12.47 • n=5 Participants	53.06 years STANDARD_DEVIATION 14.25 • n=7 Participants	51.15 years STANDARD_DEVIATION 13.40 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized White	13 Participants n=5 Participants	17 Participants n=7 Participants	30 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Predose (0 hr) on Day 1

Population: PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse pharmacokinetics (PK) sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above lower limit of quantification (LLOQ). LLOQ for ATM was 0.1 microgram per milliliter (mcg/ml).

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=1 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0 hr	0.1 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation NA Standard deviation was not estimable since only 1 participant was evaluable.	—

PRIMARY outcome

Timeframe: 0.42 hr Post dose on Day 1

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=17 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0.42 hr	39.0 mcg/mL Geometric Coefficient of Variation 262.0	39.4 mcg/mL Geometric Coefficient of Variation 58.1

PRIMARY outcome

Timeframe: 3.25 hr Post dose on Day 1

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=17 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 3.25 hr	55.7 mcg/mL Geometric Coefficient of Variation 16.0	58.5 mcg/mL Geometric Coefficient of Variation 36.3

PRIMARY outcome

Timeframe: 5 hr Post dose on Day 1

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=17 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 5 hr	28.8 mcg/mL Geometric Coefficient of Variation 23.9	31.5 mcg/mL Geometric Coefficient of Variation 50.8

PRIMARY outcome

Timeframe: Predose (0 hr) on Day 1

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 nanogram per milliliter (ng/ml).

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=1 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0 hr	24.9 nanogram per milliliter (ng/mL) Standard Deviation NA Standard deviation was not estimable since only 1 participant was evaluable.	—

PRIMARY outcome

Timeframe: 0.42 hr Post dose on Day 1

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=17 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0.42 hr	7852.6 ng/mL Geometric Coefficient of Variation 279.2	9801.5 ng/mL Geometric Coefficient of Variation 61.8

PRIMARY outcome

Timeframe: 3.25 hr Post dose on Day 1

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=17 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 3.25 hr	9976.5 ng/mL Geometric Coefficient of Variation 25.8	12982.7 ng/mL Geometric Coefficient of Variation 49.7

PRIMARY outcome

Timeframe: 5 hr Post dose on Day 1

Population: PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=17 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 5 hr	4086.6 ng/mL Geometric Coefficient of Variation 35.3	5549.0 ng/mL Geometric Coefficient of Variation 76.6

PRIMARY outcome

Timeframe: Predose (0 hr) on Day 4

Population: PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=8 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 0 hr	19.7 mcg/mL Geometric Coefficient of Variation 29.0	—

PRIMARY outcome

Timeframe: 2.75 hr Post dose on Day 4

Population: PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=8 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 2.75 hr	46.4 mcg/mL Geometric Coefficient of Variation 19.5	—

PRIMARY outcome

Timeframe: 5 hr Post dose on Day 4

Population: PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=8 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 5 hr	16.5 mcg/mL Geometric Coefficient of Variation 37.3	—

PRIMARY outcome

Timeframe: Predose (0 hr) on Day 4

Population: PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=8 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 0 hr	4048.8 ng/mL Geometric Coefficient of Variation 24.3	—

PRIMARY outcome

Timeframe: 2.75 hr Post dose on Day 4

Population: PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=8 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 2.75 hr	9073.6 ng/mL Geometric Coefficient of Variation 24.2	—

PRIMARY outcome

Timeframe: 5 hr Post dose on Day 4

Population: PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=8 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 5 hr	2745.7 ng/mL Geometric Coefficient of Variation 40.5	—

PRIMARY outcome

Timeframe: Predose (0 hr) on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0 hr	18.3 mcg/mL Geometric Coefficient of Variation 71.2	20.3 mcg/mL Geometric Coefficient of Variation 88.5

PRIMARY outcome

Timeframe: 0.5 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0.5 hr	37.6 mcg/mL Geometric Coefficient of Variation 194.0	33.8 mcg/mL Geometric Coefficient of Variation 46.0

PRIMARY outcome

Timeframe: 1 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 1 hr	41.2 mcg/mL Geometric Coefficient of Variation 53.5	43.0 mcg/mL Geometric Coefficient of Variation 44.7

PRIMARY outcome

Timeframe: 2 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 2 hr	49.6 mcg/mL Geometric Coefficient of Variation 42.5	53.6 mcg/mL Geometric Coefficient of Variation 44.7

PRIMARY outcome

Timeframe: 3 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3 hr	53.6 mcg/mL Geometric Coefficient of Variation 72.0	54.7 mcg/mL Geometric Coefficient of Variation 42.1

PRIMARY outcome

Timeframe: 3.25 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.25 hr	45.8 mcg/mL Geometric Coefficient of Variation 36.7	47.3 mcg/mL Geometric Coefficient of Variation 49.8

PRIMARY outcome

Timeframe: 3.5 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.5 hr	42.9 mcg/mL Geometric Coefficient of Variation 37.9	43.2 mcg/mL Geometric Coefficient of Variation 52.1

PRIMARY outcome

Timeframe: 3.75 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.75 hr	39.5 mcg/mL Geometric Coefficient of Variation 41.8	38.5 mcg/mL Geometric Coefficient of Variation 57.6

PRIMARY outcome

Timeframe: 4 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 4 hr	34.2 mcg/mL Geometric Coefficient of Variation 44.2	36.6 mcg/mL Geometric Coefficient of Variation 63.3

PRIMARY outcome

Timeframe: 5 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 5 hr	23.8 mcg/mL Geometric Coefficient of Variation 56.1	26.4 mcg/mL Geometric Coefficient of Variation 76.8

PRIMARY outcome

Timeframe: 6 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 6 hr	22.2 mcg/mL Geometric Coefficient of Variation 149.8	19.0 mcg/mL Geometric Coefficient of Variation 97.1

PRIMARY outcome

Timeframe: Predose (0 hr) on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0 hr	2516.2 ng/mL Geometric Coefficient of Variation 85.6	3184.3 ng/mL Geometric Coefficient of Variation 137.5

PRIMARY outcome

Timeframe: 0.5 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0.5 hr	6374.4 ng/mL Geometric Coefficient of Variation 215.4	7140.3 ng/mL Geometric Coefficient of Variation 69.3

PRIMARY outcome

Timeframe: 1 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 1 hr	7369.8 ng/mL Geometric Coefficient of Variation 59.2	9435.7 ng/mL Geometric Coefficient of Variation 64.4

PRIMARY outcome

Timeframe: 2 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 2 hr	8885.4 ng/mL Geometric Coefficient of Variation 48.5	11668.0 ng/mL Geometric Coefficient of Variation 59.5

PRIMARY outcome

Timeframe: 3 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3 hr	9820.4 ng/mL Geometric Coefficient of Variation 100.1	11903.2 ng/mL Geometric Coefficient of Variation 62.6

PRIMARY outcome

Timeframe: 3.25 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.25 hr	8009.9 ng/mL Geometric Coefficient of Variation 38.7	9631.5 ng/mL Geometric Coefficient of Variation 66.0

PRIMARY outcome

Timeframe: 3.5 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.5 hr	7095.8 ng/mL Geometric Coefficient of Variation 43.9	8545.4 ng/mL Geometric Coefficient of Variation 83.8

PRIMARY outcome

Timeframe: 3.75 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.75 hr	6340.3 ng/mL Geometric Coefficient of Variation 50.3	7227.1 ng/mL Geometric Coefficient of Variation 88.4

PRIMARY outcome

Timeframe: 4 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 4 hr	5258.7 ng/mL Geometric Coefficient of Variation 49.9	6727.6 ng/mL Geometric Coefficient of Variation 94.2

PRIMARY outcome

Timeframe: 5 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 5 hr	3300.0 ng/mL Geometric Coefficient of Variation 59.7	4300.3 ng/mL Geometric Coefficient of Variation 120.9

PRIMARY outcome

Timeframe: 6 hr Post dose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 6 hr	3275.7 ng/mL Geometric Coefficient of Variation 205.4	2879.2 ng/mL Geometric Coefficient of Variation 140.1

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Maximum Observed Plasma Concentration (Cmax) of Aztreonam (ATM): Intensive Sampling at Day 4	62.5 mcg/mL Geometric Coefficient of Variation 146.9	55.4 mcg/mL Geometric Coefficient of Variation 42.6

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Maximum Observed Plasma Concentration (Cmax) of Avibactam (AVI): Intensive Sampling at Day 4	11552.4 ng/mL Geometric Coefficient of Variation 164.5	12116.2 ng/mL Geometric Coefficient of Variation 61.2

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Time of Observed Maximum Concentration (Tmax) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 ATM	2.9 hours Interval 0.5 to 3.5	2.4 hours Interval 2.0 to 3.0
Time of Observed Maximum Concentration (Tmax) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 AVI	2.9 hours Interval 0.5 to 3.8	2.8 hours Interval 2.0 to 3.3

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) for Aztreonam (ATM): Intensive Sampling at Day 4	235.2 hourmicrogram/milliliter (hrmcg/mL) Geometric Coefficient of Variation 60.6	234.7 hourmicrogram/milliliter (hrmcg/mL) Geometric Coefficient of Variation 54.6

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) for Avibactam (AVI): Intensive Sampling at Day 4	40437.0 hournanogram per milliliter (hrng/mL) Geometric Coefficient of Variation 74.0	47477.5 hournanogram per milliliter (hrng/mL) Geometric Coefficient of Variation 79.2

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

AUC(0-last) was defined as the area under the plasma concentration-time curve from time zero up to the time of the last measurable concentration.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Area Under the Plasma Concentration Time Curve From Time Zero up to the Last Measured Concentration (AUC[0-last]) for Aztreonam (ATM): Intensive Sampling at Day 4	235.9 hr*mcg/mL Geometric Coefficient of Variation 60.4	234.3 hr*mcg/mL Geometric Coefficient of Variation 54.7

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

AUC(0-last) was defined as the area under the plasma concentration-time curve from time zero up to the time of the last measurable concentration.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Area Under the Plasma Concentration Time Curve From Time Zero up to the Last Measured Concentration (AUC[0-last]) for Avibactam (AVI): Intensive Sampling at Day 4	40539.5 hr*ng/mL Standard Deviation 73.8	47422.2 hr*ng/mL Standard Deviation 79.3

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Time of Last Measured Concentration (Tlast) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 ATM	6.0 hours Interval 6.0 to 6.5	6.0 hours Interval 5.9 to 6.0
Time of Last Measured Concentration (Tlast) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 AVI	6.0 hours Interval 6.0 to 6.5	6.0 hours Interval 5.9 to 6.0

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Plasma elimination half-life was defined as time measured for the plasma concentration of ATM and AVI to decrease by one half of its initial concentration.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=11 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Plasma Elimination Half-life (t1/2) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 ATM	2.3 hours Standard Deviation 1.06	2.8 hours Standard Deviation 2.05
Plasma Elimination Half-life (t1/2) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 AVI	1.8 hours Standard Deviation 0.59	2.2 hours Standard Deviation 1.85

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Apparent volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=11 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Apparent Volume of Distribution at Steady State (Vss) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 AVI	26.0 liter Geometric Coefficient of Variation 22.0	23.7 liter Geometric Coefficient of Variation 29.7
Apparent Volume of Distribution at Steady State (Vss) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 ATM	20.3 liter Geometric Coefficient of Variation 16.9	19.6 liter Geometric Coefficient of Variation 31.8

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=11 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Volume of Distribution (Vz) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 ATM	21.4 liter Standard Deviation 15.3	21.6 liter Standard Deviation 24.1
Volume of Distribution (Vz) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 AVI	28.2 liter Standard Deviation 20.4	27.4 liter Standard Deviation 20.6

PRIMARY outcome

Timeframe: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Population: The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=8 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Apparent Clearance (CL) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 AVI	10.1 liter/hour Geometric Coefficient of Variation 42.6	10.5 liter/hour Geometric Coefficient of Variation 41.4
Apparent Clearance (CL) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 ATM	6.4 liter/hour Geometric Coefficient of Variation 35.4	6.4 liter/hour Geometric Coefficient of Variation 35.5

PRIMARY outcome

Timeframe: From first dose of study drug up to the LFU visit (up to maximum of 38 days)

Population: The safety analysis included all enrolled participants who received any amount of study drug.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAEs was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or was an important medical event which may jeopardise the participants or require medical intervention to prevent one of the above outcomes. Treatment-emergent were events between first infusion of study drug and up to late follow-up (LFU) visit (20 to 24 days after last infusion). AEs included both non-serious AEs and SAEs.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=18 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	11 Participants	12 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	4 Participants	5 Participants

PRIMARY outcome

Timeframe: Baseline up to EOT (up to a maximum of 15 days)

Population: The safety analysis included all enrolled participants who received any amount of study drug.

Criteria for ECG abnormalities: QT value: greater than or equal to (\>=) 450 milliseconds (msec), \>=480 msec, \>=500 msec, \>=500 and increase from baseline \>=60 msec. Increase from baseline in QT: \>=30 msec, \>=60 msec. Decrease from baseline in QT: \>=30 msec, \>=60 msec. QTcB value: \>=450 msec, \>=480 msec, \>=500 msec, \>=500 and increase from baseline \>=60 msec. Increase from baseline in QT interval using Bazett's correction (QTcB) value: \>=30 msec, \>=60 msec. Decrease from baseline in QTcB: \>=30 msec, \>=60 msec. QT interval using Fridericia's correction (QTcF) value: \>=450 msec, \>=480 msec, \>=500 msec, \>=500 and increase from baseline \>=60 msec. Increase from baseline in QTcF value: \>=30 msec, \>=60 msec. Decrease from baseline in QTcF value: \>=30 msec, \>=60 msec. EOT (end of treatment) visit occurred within 24 hours after last infusion.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=18 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Number of Participants With Electrocardiogram (ECG) Abnormalities QT value >=500	2 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT value >=500 and increase from baseline >=60	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Increase in QT >=30	6 Participants	4 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Increase in QT>=60	2 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Decrease in QT >=30	1 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB value >=450	5 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB value >=500	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB value >=500 and increase from baseline >=60	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Increase in QTcB >=30	3 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Increase in QTcB >=60	0 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Decrease in QTcB >=30	2 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Decrease in QTcB >=60	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF value >=450	4 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF value >=500	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF value >=500 and increase from baseline >=60	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Decrease in QT>=60	0 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB value >=480	2 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF value >=480	2 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Increase in QTcF >=30	3 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Increase in QTcF >=60	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Decrease in QTcF >=30	0 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Decrease in QTcF >=60	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT value >=450	2 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT value >=480	2 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to LFU visit (up to maximum of 38 days)

Population: The safety analysis included all enrolled participants who received any amount of study drug. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Criteria for abnormality: Hemoglobin, hematocrit, erythrocytes less than(\<) 0.7\*lower limit of normal \[LLN\] and (\&) greater than (\>) 30 percent (%) below baseline \[BB\]; \>1.3\*upper limit of normal \[ULN\] \& \>30% above baseline \[AB\], leukocytes \<0.65\*LLN \& \>60% BB; \>1.6\* ULN \& \>100% AB; platelets \<0.65\*LLN \& \>50% BB; \>1.5\*ULN \& \>100% AB; neutrophils \<0.65\*LLN \& \>75% BB; \>1.6\*ULN \& \>100% AB, lymphocytes \<0.25\*LLN \& \>75%BB; \>1.5\*ULN \& \>100% AB, basophils, eosinophils, monocytes\>4.0\*ULN \& \>300% AB. LFU visit occurred within 20 to 24 days after last infusion.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=17 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Hemoglobin: <0.7*LLN&>30% BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Hemoglobin: >1.3*ULN&>30% AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Hematocrit: <0.7*LLN&>30% BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Hematocrit:>1.3*ULN&>30% AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Erythrocytes:<0.7*LLN&>30% BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Erythrocytes: >1.3*ULN&>30% AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Leukocytes:>1.6* ULN&>100%AB	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Neutrophils:<0.65*LLN&>75% BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Neutrophils: >1.6*ULN & >100% AB	1 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Leukocytes: <0.65*LLN&>60%BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Platelets: <0.65*LLN&>50%BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Platelets: >1.5*ULN&>100% AB	1 Participants	5 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Lymphocytes: <0.25*LLN&>75%BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Lymphocytes: >1.5*ULN&>100%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Basophils: >4.0*ULN&>300% AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Eosinophils: >4.0*ULN&>300% AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters Monocytes: >4.0*ULN&>300% AB	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to LFU visit (up to maximum of 38 days)

Population: The safety analysis included all enrolled participants who received any amount of study drug. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Criteria for abnormality: aspartate aminotransferase, alanine aminotransferase \>3.0\*ULN \& \>100% AB, alkaline phosphatase \<0.5 \*LLN \& \>80% BB\&; \>3.0\*ULN \& \>100% AB; bilirubin \>1.5\*ULN \& \>100% AB; direct bilirubin \>2.0\*ULN \& \>150% AB; protein \<0.5\*LLN \& \>50%BB; \>1.5\*ULN \& \>50% AB, albumin \<0.5\*LLN \& \>50% BB; \>1.5\*ULN \& \>50% AB, urea nitrogen \<0.2\* LLN \& \>100% BB; \>3.0\*ULN \& \>200% AB, creatinine \>2.0\*ULN \& \>100% AB, sodium \<0.85\*LLN \& \>10% BB;\>1.1\*ULN \&\>10% AB; potassium \<0.8\*LLN \&\>20% BB; \>1.2\*ULN \&\>20% AB, chloride \<0.8\*LLN \&\>20% BB;\>1.2\*ULN \& \>20% AB, calcium \<0.7\*LLN \& \>30% BB; \>1.3\*ULN \& \>30% AB, phosphate \<0.5\*LLN \& \>50% BB; \>3.0\*ULN \& \>200% AB, bicarbonate \<0.7\*LLN \& \>40% BB; \>1.3\*ULN \& \>40% AB, glucose \<0.6\*LLN \& \>40% BB, \>3.0\*ULN \& \>200% AB. LFU visit occurred within 20 to 24 days after last infusion.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=13 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=17 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Potassium: <0.8*LLN&>20%BB	1 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Bicarbonate: >1.3*ULN&>40%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Glucose: >3.0*ULN&>200%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Aspartate aminotransferase: >3.0*ULN&>100% AB	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Alanine aminotransferase:>3.0x ULN	2 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Alkaline phosphatase: <0.5 *LLN&>80% BB&	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Alkaline phosphatase:>3.0*ULN&>100%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Bilirubin: >1.5*ULN&>100%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Direct Bilirubin : >2.0*ULN&>150% AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Protein: <0.5*LLN &>50%BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Protein: >1.5*ULN&>50% AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Albumin: <0.5*LLN&>50%BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Albumin: >1.5*ULN&>50%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Urea nitrogen: <0.2* LLN&>100%BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Urea nitrogen: >3.0*ULN&>200%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Creatinine: >2.0*ULN&>100%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Sodium: < 0.85*LLN&>10%BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Sodium: >1.1*ULN&>10%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Potassium: >1.2*ULN&>20%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Chloride: <0.8*LLN&>20%BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Chloride: >1.2*ULN&>20%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Calcium: <0.7*LLN&>30% BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Calcium: >1.3*ULN&>30%AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Phosphate: <0.5*LLN&>50% BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Phosphate: >3.0*ULN&>200% AB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Bicarbonate: <0.7*LLN&>40% BB	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres Glucose: <0.6*LLN&>40% BB	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to LFU visit (up to maximum of 38 days)

Population: The safety analysis included all enrolled participants who received any amount of study drug.

Vital sign parameters included: Supine systolic blood pressure (millimeters of mercury \[mmHg\]), Supine diastolic blood pressure (mmHg), Heart rate (beats per minute), Respiratory rate (breaths per minute) and body temperature (degree celsius). Criteria for clinical significance in vital signs was based on investigator's assessment. LFU visit occurred within 20 to 24 days after last infusion.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=18 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Number of Participants With Clinically Significant Vital Signs Respiratory rate	0 Participants	1 Participants
Number of Participants With Clinically Significant Vital Signs Supine systolic blood pressure	0 Participants	0 Participants
Number of Participants With Clinically Significant Vital Signs Supine diastolic blood pressure	0 Participants	0 Participants
Number of Participants With Clinically Significant Vital Signs Heart rate	0 Participants	0 Participants
Number of Participants With Clinically Significant Vital Signs Temperature	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to the LFU visit (up to maximum of 38 days)

Population: The MITT population included all enrolled participants who received any amount of study drug. Here, 'number analysed' = Participants evaluable for this outcome measure at specified categories.

Physical examinations included an assessment of abdomen, cardiovascular, general appearance, head, eyes, ears, nose, lymph nodes, skin, musculoskeletal, neurological, respiratory systems and other (edemas). Clinically significant abnormality in physical examination was based on investigator's assessment. LFU visit occured within 20 to 24 days after last infusion.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=18 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population Cardiovascular	0 Participants	0 Participants
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population Respiratory system	0 Participants	1 Participants
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population Abdomen	1 Participants	0 Participants
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population General appearance	0 Participants	1 Participants
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population Head, Eyes, Ears, Nose	0 Participants	0 Participants
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population Lymph nodes	0 Participants	0 Participants
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population Musculoskeletal system	0 Participants	0 Participants
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population Neurological system	0 Participants	0 Participants
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population Other	0 Participants	1 Participants
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population Skin	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Test of Cure Visit (up to a maximum of 28 days)

Population: The MITT population included all enrolled participants who received any amount of study drug.

Clinical cure is defined as complete resolution or significant improvement of signs and symptoms of the index infection (cIAI) such as no further antimicrobial therapy, drainage, or surgical intervention is necessary and does not meet any of the failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within the abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. TOC visit occurred up to a maximum of 28 days after first dose.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=18 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: MITT Population	62.5 percentage of participants Interval 35.4 to 84.8	55.6 percentage of participants Interval 30.8 to 78.5

SECONDARY outcome

Timeframe: Test of Cure Visit (up to a maximum of 28 days)

Population: The mMITT population included all enrolled participants who had any amount of study drug and had a diagnosis of cIAI (that is,met inclusion criterion ) and an intraabdominal pathogen at baseline. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Clinical cure is defined as complete resolution or significant improvement of signs and symptoms of the index infection (cIAI) such as no further antimicrobial therapy, drainage, or surgical intervention is necessary and does not meet any of the failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within the abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. TOC visit occurred up to a maximum of 28 days after first dose.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=11 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Percentage of Participants With Clinical Cure at TOC Visit: Microbiologically Modified Intent-to-Treat (mMITT) Population	66.7 percentage of participants Interval 34.9 to 90.1	54.5 percentage of participants Interval 23.4 to 83.3

SECONDARY outcome

Timeframe: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)

Population: The MITT population included all enrolled participants who received any amount of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories. AUC0-6 was assessed on Day 4 and presented in this OM, only for those participants who had clinical cure or failure at TOC visit.

AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=18 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population) Clinical Cure	226.0 hr*mcg/mL Geometric Coefficient of Variation 43.0	218.7 hr*mcg/mL Geometric Coefficient of Variation 28.5
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population) Clinical Failure	268.9 hr*mcg/mL Geometric Coefficient of Variation 88.3	169.8 hr*mcg/mL Geometric Coefficient of Variation 14.9

SECONDARY outcome

Timeframe: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)

Population: The MITT population included all enrolled participants who received any amount of study drug. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified categories. AUC0-6 was assessed on Day 4 and presented in this OM, only for those participants who had clinical cure or failure at TOC visit.

AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=16 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=18 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population) Clinical Cure	38003.8 hr*ng/mL Geometric Coefficient of Variation 45.7	40314.0 hr*ng/mL Geometric Coefficient of Variation 36.1
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population) Clinical Failure	49730.0 hr*ng/mL Geometric Coefficient of Variation 100.1	34633.7 hr*ng/mL Geometric Coefficient of Variation 10.2

SECONDARY outcome

Timeframe: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)

Population: mMITTpopulation set was used in this analysis. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified categories. AUC0-6 was assessed on Day 4 and presented in this OM, only for those participants who had clinical cure or failure at TOC visit.

AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=11 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population) Clinical Cure	245.3 hr*mcg/mL Geometric Coefficient of Variation 41.4	292.7 hr*mcg/mL Geometric Coefficient of Variation NA Standard deviation was not estimable since only 1 participant was evaluable.
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population) Clinical Failure	378.0 hr*mcg/mL Geometric Coefficient of Variation 77.0	—

SECONDARY outcome

Timeframe: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)

Population: mMITTpopulation set was used in this analysis. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified categories. AUC0-6 was assessed on Day 4 and presented in this OM, only for those participants who had clinical cure or failure at TOC visit.

AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.

Outcome measures

Outcome measures
Measure	ATM-AVI+ Metronidazole:Low AVI Dose Cohort n=12 Participants Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=11 Participants Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population) Clinical Cure	42401.9 hr*ng/mL Geometric Coefficient of Variation 41.9	60302.1 hr*ng/mL Geometric Coefficient of Variation NA Standard deviation was not estimable since only 1 participant was evaluable.
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population) Clinical Failure	75509.9 hr*ng/mL Geometric Coefficient of Variation 84.3	—

Adverse Events

ATM-AVI+ Metronidazole: Low AVI Dose Cohort

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

ATM-AVI + Metronidazole: High AVI Dose Cohort

Serious events: 5 serious events

Other events: 10 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	ATM-AVI+ Metronidazole: Low AVI Dose Cohort n=16 participants at risk Participants with normal renal function or mild renal impairment (CrCl \> 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.	ATM-AVI + Metronidazole: High AVI Dose Cohort n=18 participants at risk Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment \[CrCl \>50mL/min\] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment \[CrCl 31-50 ml/min\]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	5.6% 1/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Gastrointestinal disorders Intra-abdominal haematoma	0.00% 0/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	5.6% 1/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	5.6% 1/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Infections and infestations Abdominal wall infection	6.2% 1/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	0.00% 0/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Infections and infestations Sepsis	6.2% 1/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	0.00% 0/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Injury, poisoning and procedural complications Arterial injury	0.00% 0/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	5.6% 1/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Injury, poisoning and procedural complications Postoperative ileus	0.00% 0/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	5.6% 1/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	6.2% 1/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	0.00% 0/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Renal and urinary disorders Acute kidney injury	0.00% 0/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	5.6% 1/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	6.2% 1/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	0.00% 0/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Respiratory distress	6.2% 1/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	0.00% 0/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	0.00% 0/16 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.	5.6% 1/18 • From first dose of study drug up to the LFU visit (up to maximum of 38 days) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results
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Restriction type: OTHER