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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02655419
• Collaborator: Innovative Medicines Initiative (IMI) COMBACTE-CARE (Other)
• Enrollment: 40
• Locations: 11
• Arm: 1
• Actual Duration (Months): 17.2
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Determine the PK and safety and tolerability of aztreonam-avibactam (ATM-AVI) in the treatment of hospitalized adults with cIAI

Condition or Disease	Intervention/Treatment	Phase
Complicated Intra-Abdominal Infections, cIAIs	Drug: ATM-AVI; Drug: Metronidazole	Phase 2

Detailed Description

A Phase IIa prospective, open-label, multicenter study to determine the pharmacokinetics (PK) and safety and tolerability of aztreonam-avibactam (ATM-AVI) for the treatment of complicated Intra-Abdominal Infections (cIAIs) in hospitalized adults.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE IIA PROSPECTIVE, OPEN-LABEL, MULTICENTER STUDY TO DETERMINE THE PHARMACOKINETICS (PK) AND SAFETY AND TOLERABILITY OF AZTREONAM-AVIBACTAM (ATM-AVI) FOR THE TREATMENT OF COMPLICATED INTRA-ABDOMINAL INFECTIONS (CIAIS) IN HOSPITALIZED ADULTS
• Actual Study Start Date: May 19, 2016
• Actual Primary Completion Date: Oct 26, 2017
• Actual Study Completion Date: Oct 26, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: ATM-AVI + Metronidazole Aztreonam-avibactam + metronidazole

Drug: ATM-AVI; Cohort 1: (Creatinine clearance > 50 mL/min)6500mg ATM/1777mg AVI on day 1 followed by total daily dose of 6000mg ATM/1640mg AVI Cohorts 2 and 3: (Creatinine clearance > 50 mL/min) As above, or: 6500 mg ATM/2167 mg on Day 1 followed by a total daily dose of 6000 mg ATM/2000 m AVI (Creatinine clearance 31 - 50 mL/min) 4250 mg ATM/1162 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/820 mg AVI, or: 4250 mg ATM/1417 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/1000 mg AVI; Drug: Metronidazole; Metronidazole 500mg infused over 1 hour every 8 hours

Outcome Measures

Primary Outcome Measures

1. Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0 hr [Predose (0 hr) on Day 1]

   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).

2. Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0.42 hr [0.42 hr Post dose on Day 1]

   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.

3. Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 3.25 hr [3.25 hr Post dose on Day 1]

   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.

4. Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 5 hr [5 hr Post dose on Day 1]

   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.

5. Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0 hr [Predose (0 hr) on Day 1]

   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).

6. Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0.42 hr [0.42 hr Post dose on Day 1]

   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.

7. Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 3.25 hr [3.25 hr Post dose on Day 1]

   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.

8. Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 5 hr [5 hr Post dose on Day 1]

   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.

9. Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 0 hr [Predose (0 hr) on Day 4]

   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.

10. Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 2.75 hr [2.75 hr Post dose on Day 4]

    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.

11. Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 5 hr [5 hr Post dose on Day 4]

    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.

12. Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 0 hr [Predose (0 hr) on Day 4]

    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.

13. Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 2.75 hr [2.75 hr Post dose on Day 4]

    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.

14. Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 5 hr [5 hr Post dose on Day 4]

    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.

15. Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0 hr [Predose (0 hr) on Day 4]

    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.

16. Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0.5 hr [0.5 hr Post dose on Day 4]

    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.

17. Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 1 hr [1 hr Post dose on Day 4]

    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.

18. Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 2 hr [2 hr Post dose on Day 4]

    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.

19. Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3 hr [3 hr Post dose on Day 4]

    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.

20. Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.25 hr [3.25 hr Post dose on Day 4]

    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.

21. Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.5 hr [3.5 hr Post dose on Day 4]

    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.

22. Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.75 hr [3.75 hr Post dose on Day 4]

    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.

23. Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 4 hr [4 hr Post dose on Day 4]

    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.

24. Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 5 hr [5 hr Post dose on Day 4]

    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.

25. Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 6 hr [6 hr Post dose on Day 4]

    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.

26. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0 hr [Predose (0 hr) on Day 4]

    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.

27. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0.5 hr [0.5 hr Post dose on Day 4]

    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.

28. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 1 hr [1 hr Post dose on Day 4]

    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.

29. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 2 hr [2 hr Post dose on Day 4]

    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.

30. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3 hr [3 hr Post dose on Day 4]

    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.

31. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.25 hr [3.25 hr Post dose on Day 4]

    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.

32. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.5 hr [3.5 hr Post dose on Day 4]

    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.

33. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.75 hr [3.75 hr Post dose on Day 4]

    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.

34. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 4 hr [4 hr Post dose on Day 4]

    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.

35. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 5 hr [5 hr Post dose on Day 4]

    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.

36. Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 6 hr [6 hr Post dose on Day 4]

    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.

37. Maximum Observed Plasma Concentration (Cmax) of Aztreonam (ATM): Intensive Sampling at Day 4 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

38. Maximum Observed Plasma Concentration (Cmax) of Avibactam (AVI): Intensive Sampling at Day 4 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

39. Time of Observed Maximum Concentration (Tmax) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

40. 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 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

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

41. 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 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

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

42. 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 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

    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.

43. 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 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

    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.

44. Time of Last Measured Concentration (Tlast) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

45. Plasma Elimination Half-life (t1/2) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

    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.

46. Apparent Volume of Distribution at Steady State (Vss) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

    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.

47. Volume of Distribution (Vz) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

    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.

48. Apparent Clearance (CL) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4]

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

49. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [From first dose of study drug up to the LFU visit (up to maximum of 38 days)]

    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.

50. Number of Participants With Electrocardiogram (ECG) Abnormalities [Baseline up to EOT (up to a maximum of 15 days)]

    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.

51. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters [Baseline up to LFU visit (up to maximum of 38 days)]

    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.

52. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres [Baseline up to LFU visit (up to maximum of 38 days)]

    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.

53. Number of Participants With Clinically Significant Vital Signs [From first dose of study drug up to LFU visit (up to maximum of 38 days)]

    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.

54. Number of Participants With Clinical Significant Physical Examination Findings : MITT Population [From first dose of study drug up to the LFU visit (up to maximum of 38 days)]

    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.

Secondary Outcome Measures

1. Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: MITT Population [Test of Cure Visit (up to a maximum of 28 days)]

   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.

2. Percentage of Participants With Clinical Cure at TOC Visit: Microbiologically Modified Intent-to-Treat (mMITT) Population [Test of Cure Visit (up to a maximum of 28 days)]

   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.

3. 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) [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)]

   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.

4. 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) [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)]

   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.

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 (mMITT Population) [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)]

   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.

6. 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) [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)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Provision of informed consent

2. Male or female from 18 to 90 years

3. Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met

4. Diagnosis of cIAI

EITHER:

Intra-operative/postoperative enrolment with visual confirmation of cIAI. OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry

1. Patients who failed prior antibacterial treatment for their current cIAI can be enrolled but must:

• Have a known or suspected pathogen causing cIAI that is resistant to the prior therapy

• Require surgical intervention.

1. Patient must have or will have a surgical intervention within 24 hours (before or after) the administration of the first dose of study drug

Exclusion criteria:

1. Involvement in the planning and/or conduct of the study

2. Patient has been previously enrolled in this study, previously treated with ATM-AVI or previously participated in an investigational study containing AVI

3. Patient has participated or intends to participate in any other clinical study that involves the administration of a study drug during the course of the study, or during the 30 days prior to study start.

4. History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem,monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs

5. Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery within 24 hours of diagnosis primary etiology is not likely to be infectious

6. Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess or ischaemic/necrotic intestine without perforation

7. Staged abdominal repair (STAR), open abdomen technique or where infection source control is not likely to be achieved; unlikely to solely respond to antimicrobial therapy

8. Infection due to a pathogen that is unlikely to respond to ATM-AVI plus metronidazole

9. Rapidly progressive or terminal illness

10. Systemic antibacterial agents received within the 72- hour period prior to study entry, unless:

11. A new infection and no more than 24 hours of prior antibiotic treatment received within the 72 hour period prior to study entry or

12. Patient is considered to have failed the previous treatment

13. Concurrent infection that may interfere with the evaluation of clinical cure for the study therapy

14. requirement for effective concomitant systemic antibacterials or antifungals

15. Creatinine clearance ≤30 ml/min or requirement for renal replacement therapy

16. Acute hepatitis in the prior 6 months, chronic hepatitis, cirrhosis, acute hepatic failure, or acute decompensation of chronic hepatic failure

17. Hepatic disease as indicated by AST or ALT >3 × ULN. Patients with AST and/or ALT >3 × ULN and < 5 × ULN are eligible if acute, not accompanied by a total bilirubin ≥ 2xULN and documented by the investigator as being directly related to cIAI.

18. Patient has a total bilirubin >3 × ULN, unless isolated hyperbilirubinemia is directly related to cIAI or due to known Gilbert's disease

19. ALP >3 × ULN. Patients with values >3 × ULN and <5 x ULN are eligible if acute and directly related to the infectious process being treated.

20. Immunocompromising illness

21. Active Clostridium difficile associated diarrhoea

22. Any other condition that may confound the results of the study or pose additional risks

23. Do not resuscitate order

24. Absolute neutrophil count <1000/μL

25. Hematocrit <25% or hemoglobin <8 gm/dL.

26. Platelet count <75,000/μL.

27. Currently receiving probenecid.

28. Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control.

29. Unlikely to comply with protocol,

30. Currently receiving anti-convulsant therapy to prevent recurrence of a past history of seizures.

31. Prior liver, pancreas or small-bowel transplant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital C.	Lille Cedex		France	59037
2	CHU Limoges	Limoges cedex		France	87042
3	Universitaetsklinikum Koeln Innere Medizin I	Koeln		Germany	50937
4	Universitaetsklinikum Schleswig-Holstein, Klinik fuer Infektiologie und Mikrobiologie, DZIF-CTU	Luebeck		Germany	23538
5	Hospital Universitario Cruces	Barakaldo	Bizkaia	Spain	48903
6	Hospital Universitario Son Espases	Palma de Mallorca	ISLA Baleares	Spain	07010
7	Hospital Universitari del Mar	Barcelona		Spain	08003
8	Hospital Universitario Reina Sofia	Cordoba		Spain	14004
9	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
10	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
11	Hospital Universitario Mutua de Tarrasa	Terrassa		Spain	08221

Sponsors and Collaborators

• Pfizer
• Innovative Medicines Initiative (IMI) COMBACTE-CARE

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer
• Principal Investigator: Oliver Cornely, Clinical Trials Centre Cologne

Study Documents (Full-Text)

• Study Protocol - Mar 29, 2017
• Statistical Analysis Plan - Jul 4, 2016

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02655419
• Other Study ID Numbers: D4910C00009; C3601001; 2015-002726-39
• First Posted: Jan 14, 2016
• Last Update Posted: Apr 2, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Pfizer: cIAIs in hospitalized adults
• Additional relevant MeSH terms: Infections; Intraabdominal Infections; Metronidazole

Study Results

Participant Flow

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

Arm/Group Title	Aztreonam-Avibactam(ATM-AVI)+Metronidazole:Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	17	23
Treated	16	18
COMPLETED	12	16
NOT COMPLETED	5	7

Baseline Characteristics

Arm/Group Title	ATM-AVI+ Metronidazole:Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	16	18	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.00 (12.47)	53.06 (14.25)	51.15 (13.40)
Sex: Female, Male (Count of Participants)
Female	4 25%	4 22.2%	8 23.5%
Male	12 75%	14 77.8%	26 76.5%
Race/Ethnicity, Customized (Count of Participants)
White	13 81.3%	17 94.4%	30 88.2%
Other	1 6.3%	0 0%	1 2.9%
Unknown	1 6.3%	1 5.6%	2 5.9%
Native Hawaiian or Other Pacific Islander	1 6.3%	0 0%	1 2.9%

Outcome Measures

1. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0 hr
Description	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).
Time Frame	Predose (0 hr) on Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI+ Metronidazole:Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	1	0
Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter (mcg/mL)]	0.1 (NA)

2. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0.42 hr
Description	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.
Time Frame	0.42 hr Post dose on Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ATM-AVI+ Metronidazole:Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	39.0 (262.0)	39.4 (58.1)

3. Primary Outcome

Title	Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 3.25 hr
Description	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.
Time Frame	3.25 hr Post dose on Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI+ Metronidazole:Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	55.7 (16.0)	58.5 (36.3)

4. Primary Outcome

Title	Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 5 hr
Description	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.
Time Frame	5 hr Post dose on Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	28.8 (23.9)	31.5 (50.8)

5. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0 hr
Description	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).
Time Frame	Predose (0 hr) on Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	1	0
Geometric Mean (Standard Deviation) [nanogram per milliliter (ng/mL)]	24.9 (NA)

6. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0.42 hr
Description	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.
Time Frame	0.42 hr Post dose on Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	7852.6 (279.2)	9801.5 (61.8)

7. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 3.25 hr
Description	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.
Time Frame	3.25 hr Post dose on Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	9976.5 (25.8)	12982.7 (49.7)

8. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 5 hr
Description	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.
Time Frame	5 hr Post dose on Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	4086.6 (35.3)	5549.0 (76.6)

9. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 0 hr
Description	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.
Time Frame	Predose (0 hr) on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	19.7 (29.0)

10. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 2.75 hr
Description	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.
Time Frame	2.75 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	46.4 (19.5)

11. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 5 hr
Description	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.
Time Frame	5 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	16.5 (37.3)

12. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 0 hr
Description	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.
Time Frame	Predose (0 hr) on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	4048.8 (24.3)

13. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 2.75 hr
Description	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.
Time Frame	2.75 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	9073.6 (24.2)

14. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 5 hr
Description	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.
Time Frame	5 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	2745.7 (40.5)

15. Primary Outcome

Title	Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0 hr
Description	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.
Time Frame	Predose (0 hr) on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	18.3 (71.2)	20.3 (88.5)

16. Primary Outcome

Title	Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0.5 hr
Description	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.
Time Frame	0.5 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	Higher AVI Dose (Cohorts 2+3)
Arm/Group Description	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.	Participants with cIAI, having CrCl >50mL/min, received ATM plus AVI at loading dose of 500mg ATM plus higher dose AVI(167mg), IV for 30minute period, followed by maintenance infusions of 1500mg ATM plus 500mg AVI, over 3hr period every 6hrs, for maximum of 14days. Participants with CrCl 31-50mL/min, either received loading dose consistent with Cohort 1, followed by extended loading infusion of 1500mg ATM plus 410mg AVI over 3hr period, followed by(3hrs after stop of second loading infusion) maintenance infusion of 750mg ATM plus 205mg AVI over 3hr period(administered every 6hrs) or loading dose consistent with higher AVI dose in Cohort 2, followed by extended loading infusion of 1500mg ATM plus 500mg AVI over 3hrperiod, followed by maintenance infusion of 750mg ATM plus 250mg AVI over 3hr period(administered every 6hrs). Participants also received 500mg metronidazole infused over 1hr every 8hrs after first ATM-AVI maintenance infusion(Day5 to Day14) at investigator's discretion.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	37.6 (194.0)	33.8 (46.0)

17. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 1 hr
Description	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.
Time Frame	1 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	41.2 (53.5)	43.0 (44.7)

18. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 2 hr
Description	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.
Time Frame	2 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	49.6 (42.5)	53.6 (44.7)

19. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3 hr
Description	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.
Time Frame	3 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	53.6 (72.0)	54.7 (42.1)

20. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.25 hr
Description	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.
Time Frame	3.25 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	45.8 (36.7)	47.3 (49.8)

21. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.5 hr
Description	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.
Time Frame	3.5 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	42.9 (37.9)	43.2 (52.1)

22. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.75 hr
Description	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.
Time Frame	3.75 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	39.5 (41.8)	38.5 (57.6)

23. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 4 hr
Description	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.
Time Frame	4 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	34.2 (44.2)	36.6 (63.3)

24. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 5 hr
Description	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.
Time Frame	5 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	23.8 (56.1)	26.4 (76.8)

25. Primary Outcome

Title	Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 6 hr
Description	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.
Time Frame	6 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	Higher AVI Dose (Cohorts 2+3)
Arm/Group Description	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.	Participants with cIAI, having CrCl >50mL/min, received ATM plus AVI at loading dose of 500mg ATM plus higher dose AVI(167mg), IV for 30minute period, followed by maintenance infusions of 1500mg ATM plus 500mg AVI, over 3hr period every 6hrs, for maximum of 14days. Participants with CrCl 31-50mL/min, either received loading dose consistent with Cohort 1, followed by extended loading infusion of 1500mg ATM plus 410mg AVI over 3hr period, followed by(3hrs after stop of second loading infusion) maintenance infusion of 750mg ATM plus 205mg AVI over 3hr period(administered every 6hrs) or loading dose consistent with higher AVI dose in Cohort 2, followed by extended loading infusion of 1500mg ATM plus 500mg AVI over 3hrperiod, followed by maintenance infusion of 750mg ATM plus 250mg AVI over 3hr period(administered every 6hrs). Participants also received 500mg metronidazole infused over 1hr every 8hrs after first ATM-AVI maintenance infusion(Day5 to Day14) at investigator's discretion.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	22.2 (149.8)	19.0 (97.1)

26. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0 hr
Description	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.
Time Frame	Predose (0 hr) on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	2516.2 (85.6)	3184.3 (137.5)

27. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0.5 hr
Description	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.
Time Frame	0.5 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	6374.4 (215.4)	7140.3 (69.3)

28. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 1 hr
Description	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.
Time Frame	1 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	7369.8 (59.2)	9435.7 (64.4)

29. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 2 hr
Description	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.
Time Frame	2 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	8885.4 (48.5)	11668.0 (59.5)

30. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3 hr
Description	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.
Time Frame	3 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	9820.4 (100.1)	11903.2 (62.6)

31. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.25 hr
Description	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.
Time Frame	3.25 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	8009.9 (38.7)	9631.5 (66.0)

32. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.5 hr
Description	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.
Time Frame	3.5 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	7095.8 (43.9)	8545.4 (83.8)

33. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.75 hr
Description	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.
Time Frame	3.75 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	6340.3 (50.3)	7227.1 (88.4)

34. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 4 hr
Description	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.
Time Frame	4 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	5258.7 (49.9)	6727.6 (94.2)

35. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 5 hr
Description	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.
Time Frame	5 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	3300.0 (59.7)	4300.3 (120.9)

36. Primary Outcome

Title	Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 6 hr
Description	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.
Time Frame	6 hr Post dose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	3275.7 (205.4)	2879.2 (140.1)

37. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Aztreonam (ATM): Intensive Sampling at Day 4
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	62.5 (146.9)	55.4 (42.6)

38. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Avibactam (AVI): Intensive Sampling at Day 4
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	11552.4 (164.5)	12116.2 (61.2)

39. Primary Outcome

Title	Time of Observed Maximum Concentration (Tmax) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
ATM	2.9	2.4
AVI	2.9	2.8

40. Primary Outcome

Title	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
Description	AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [hour*microgram/milliliter (hr*mcg/mL)]	235.2 (60.6)	234.7 (54.6)

41. Primary Outcome

Title	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
Description	AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [hour*nanogram per milliliter (hr*ng/mL)]	40437.0 (74.0)	47477.5 (79.2)

42. Primary Outcome

Title	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
Description	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.
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Geometric Coefficient of Variation) [hr*mcg/mL]	235.9 (60.4)	234.3 (54.7)

43. Primary Outcome

Title	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
Description	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.
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
Geometric Mean (Standard Deviation) [hr*ng/mL]	40539.5 (73.8)	47422.2 (79.3)

44. Primary Outcome

Title	Time of Last Measured Concentration (Tlast) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
ATM	6.0	6.0
AVI	6.0	6.0

45. Primary Outcome

Title	Plasma Elimination Half-life (t1/2) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Description	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.
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	11	8
ATM	2.3 (1.06)	2.8 (2.05)
AVI	1.8 (0.59)	2.2 (1.85)

46. Primary Outcome

Title	Apparent Volume of Distribution at Steady State (Vss) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Description	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.
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	11	8
ATM	20.3 (16.9)	19.6 (31.8)
AVI	26.0 (22.0)	23.7 (29.7)

47. Primary Outcome

Title	Volume of Distribution (Vz) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Description	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.
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	11	8
ATM	21.4 (15.3)	21.6 (24.1)
AVI	28.2 (20.4)	27.4 (20.6)

48. Primary Outcome

Title	Apparent Clearance (CL) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Description	Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Time Frame	predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	8
ATM	6.4 (35.4)	6.4 (35.5)
AVI	10.1 (42.6)	10.5 (41.4)

49. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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.
Time Frame	From first dose of study drug up to the LFU visit (up to maximum of 38 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	18
AEs	11 68.8%	12 66.7%
SAEs	4 25%	5 27.8%

50. Primary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Abnormalities
Description	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.
Time Frame	Baseline up to EOT (up to a maximum of 15 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	18
QT value >=450	2 12.5%	0 0%
QT value >=480	2 12.5%	0 0%
QT value >=500	2 12.5%	0 0%
QT value >=500 and increase from baseline >=60	1 6.3%	0 0%
Increase in QT >=30	6 37.5%	4 22.2%
Increase in QT>=60	2 12.5%	1 5.6%
Decrease in QT >=30	1 6.3%	1 5.6%
Decrease in QT>=60	0 0%	1 5.6%
QTcB value >=450	5 31.3%	1 5.6%
QTcB value >=480	2 12.5%	0 0%
QTcB value >=500	1 6.3%	0 0%
QTcB value >=500 and increase from baseline >=60	0 0%	0 0%
Increase in QTcB >=30	3 18.8%	1 5.6%
Increase in QTcB >=60	0 0%	1 5.6%
Decrease in QTcB >=30	2 12.5%	1 5.6%
Decrease in QTcB >=60	0 0%	0 0%
QTcF value >=450	4 25%	0 0%
QTcF value >=480	2 12.5%	0 0%
QTcF value >=500	1 6.3%	0 0%
QTcF value >=500 and increase from baseline >=60	0 0%	0 0%
Increase in QTcF >=30	3 18.8%	2 11.1%
Increase in QTcF >=60	0 0%	0 0%
Decrease in QTcF >=30	0 0%	1 5.6%
Decrease in QTcF >=60	0 0%	0 0%

51. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters
Description	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.
Time Frame	Baseline up to LFU visit (up to maximum of 38 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	17
Hemoglobin: <0.7*LLN&>30% BB	0 0%	0 0%
Hemoglobin: >1.3*ULN&>30% AB	0 0%	0 0%
Hematocrit: <0.7*LLN&>30% BB	0 0%	0 0%
Hematocrit:>1.3*ULN&>30% AB	0 0%	0 0%
Erythrocytes:<0.7*LLN&>30% BB	0 0%	0 0%
Erythrocytes: >1.3*ULN&>30% AB	0 0%	0 0%
Leukocytes: <0.65*LLN&>60%BB	0 0%	0 0%
Leukocytes:>1.6* ULN&>100%AB	1 6.3%	0 0%
Platelets: <0.65*LLN&>50%BB	0 0%	0 0%
Platelets: >1.5*ULN&>100% AB	1 6.3%	5 27.8%
Neutrophils:<0.65*LLN&>75% BB	0 0%	0 0%
Neutrophils: >1.6*ULN & >100% AB	1 6.3%	1 5.6%
Lymphocytes: <0.25*LLN&>75%BB	0 0%	0 0%
Lymphocytes: >1.5*ULN&>100%AB	0 0%	0 0%
Basophils: >4.0*ULN&>300% AB	0 0%	0 0%
Eosinophils: >4.0*ULN&>300% AB	0 0%	0 0%
Monocytes: >4.0*ULN&>300% AB	0 0%	0 0%

52. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres
Description	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.
Time Frame	Baseline up to LFU visit (up to maximum of 38 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	13	17
Aspartate aminotransferase: >3.0*ULN&>100% AB	1 6.3%	0 0%
Alanine aminotransferase:>3.0x ULN	2 12.5%	2 11.1%
Alkaline phosphatase: <0.5 *LLN&>80% BB&	0 0%	0 0%
Alkaline phosphatase:>3.0*ULN&>100%AB	0 0%	0 0%
Bilirubin: >1.5*ULN&>100%AB	0 0%	0 0%
Direct Bilirubin : >2.0*ULN&>150% AB	0 0%	0 0%
Protein: <0.5*LLN &>50%BB	0 0%	0 0%
Protein: >1.5*ULN&>50% AB	0 0%	0 0%
Albumin: <0.5*LLN&>50%BB	0 0%	0 0%
Albumin: >1.5*ULN&>50%AB	0 0%	0 0%
Urea nitrogen: <0.2* LLN&>100%BB	0 0%	0 0%
Urea nitrogen: >3.0*ULN&>200%AB	0 0%	0 0%
Creatinine: >2.0*ULN&>100%AB	0 0%	0 0%
Sodium: < 0.85*LLN&>10%BB	0 0%	0 0%
Sodium: >1.1*ULN&>10%AB	0 0%	0 0%
Potassium: <0.8*LLN&>20%BB	1 6.3%	1 5.6%
Potassium: >1.2*ULN&>20%AB	0 0%	0 0%
Chloride: <0.8*LLN&>20%BB	0 0%	0 0%
Chloride: >1.2*ULN&>20%AB	0 0%	0 0%
Calcium: <0.7*LLN&>30% BB	0 0%	0 0%
Calcium: >1.3*ULN&>30%AB	0 0%	0 0%
Phosphate: <0.5*LLN&>50% BB	0 0%	0 0%
Phosphate: >3.0*ULN&>200% AB	0 0%	0 0%
Bicarbonate: <0.7*LLN&>40% BB	0 0%	0 0%
Bicarbonate: >1.3*ULN&>40%AB	0 0%	0 0%
Glucose: <0.6*LLN&>40% BB	0 0%	0 0%
Glucose: >3.0*ULN&>200%AB	0 0%	0 0%

53. Primary Outcome

Title	Number of Participants With Clinically Significant Vital Signs
Description	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.
Time Frame	From first dose of study drug up to LFU visit (up to maximum of 38 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ATM-AVI+ Metronidazole:Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	18
Supine systolic blood pressure	0 0%	0 0%
Supine diastolic blood pressure	0 0%	0 0%
Heart rate	0 0%	0 0%
Respiratory rate	0 0%	1 5.6%
Temperature	0 0%	0 0%

54. Primary Outcome

Title	Number of Participants With Clinical Significant Physical Examination Findings : MITT Population
Description	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.
Time Frame	From first dose of study drug up to the LFU visit (up to maximum of 38 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	18
Abdomen	1 6.3%	0 0%
Cardiovascular	0 0%	0 0%
General appearance	0 0%	1 5.6%
Head, Eyes, Ears, Nose	0 0%	0 0%
Lymph nodes	0 0%	0 0%
Musculoskeletal system	0 0%	0 0%
Neurological system	0 0%	0 0%
Other	0 0%	1 5.6%
Respiratory system	0 0%	1 5.6%
Skin	0 0%	0 0%

55. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: MITT Population
Description	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.
Time Frame	Test of Cure Visit (up to a maximum of 28 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	18
Number (95% Confidence Interval) [percentage of participants]	62.5 390.6%	55.6 308.9%

56. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at TOC Visit: Microbiologically Modified Intent-to-Treat (mMITT) Population
Description	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.
Time Frame	Test of Cure Visit (up to a maximum of 28 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI + Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	11
Number (95% Confidence Interval) [percentage of participants]	66.7 416.9%	54.5 302.8%

57. Secondary Outcome

Title	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)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI+ Metronidazole:Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	18
Clinical Cure	226.0 (43.0)	218.7 (28.5)
Clinical Failure	268.9 (88.3)	169.8 (14.9)

58. Secondary Outcome

Title	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)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI+ Metronidazole:Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	16	18
Clinical Cure	38003.8 (45.7)	40314.0 (36.1)
Clinical Failure	49730.0 (100.1)	34633.7 (10.2)

59. Secondary Outcome

Title	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)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI+ Metronidazole:Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	11
Clinical Cure	245.3 (41.4)	292.7 (NA)
Clinical Failure	378.0 (77.0)

60. Secondary Outcome

Title	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)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	ATM-AVI+ Metronidazole: Low AVI Dose Cohort	ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.	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.
Measure Participants	12	11
Clinical Cure	42401.9 (41.9)	60302.1 (NA)
Clinical Failure	75509.9 (84.3)

Adverse Events

Time Frame	From first dose of study drug up to the LFU visit (up to maximum of 38 days)
Adverse Event Reporting Description	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.
Arm/Group Title	ATM-AVI+ Metronidazole: Low AVI Dose Cohort		ATM-AVI + Metronidazole: High AVI Dose Cohort
Arm/Group Description	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.		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.
All Cause Mortality
	ATM-AVI+ Metronidazole: Low AVI Dose Cohort		ATM-AVI + Metronidazole: High AVI Dose Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		1/18 (5.6%)
Serious Adverse Events
	ATM-AVI+ Metronidazole: Low AVI Dose Cohort		ATM-AVI + Metronidazole: High AVI Dose Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/16 (25%)		5/18 (27.8%)
Gastrointestinal disorders
Intestinal ischaemia	0/16 (0%)		1/18 (5.6%)
Intra-abdominal haematoma	0/16 (0%)		1/18 (5.6%)
Pancreatitis acute	0/16 (0%)		1/18 (5.6%)
Infections and infestations
Abdominal wall infection	1/16 (6.3%)		0/18 (0%)
Sepsis	1/16 (6.3%)		0/18 (0%)
Injury, poisoning and procedural complications
Arterial injury	0/16 (0%)		1/18 (5.6%)
Postoperative ileus	0/16 (0%)		1/18 (5.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/16 (6.3%)		0/18 (0%)
Renal and urinary disorders
Acute kidney injury	0/16 (0%)		1/18 (5.6%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/16 (6.3%)		0/18 (0%)
Respiratory distress	1/16 (6.3%)		0/18 (0%)
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous	0/16 (0%)		1/18 (5.6%)
Other (Not Including Serious) Adverse Events
	ATM-AVI+ Metronidazole: Low AVI Dose Cohort		ATM-AVI + Metronidazole: High AVI Dose Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/16 (62.5%)		10/18 (55.6%)
Blood and lymphatic system disorders
Anaemia	1/16 (6.3%)		2/18 (11.1%)
Thrombocytosis	1/16 (6.3%)		0/18 (0%)
Cardiac disorders
Cardiac failure congestive	1/16 (6.3%)		0/18 (0%)
Eye disorders
Vision blurred	0/16 (0%)		1/18 (5.6%)
Gastrointestinal disorders
Abdominal pain lower	0/16 (0%)		2/18 (11.1%)
Diarrhoea	2/16 (12.5%)		3/18 (16.7%)
Nausea	0/16 (0%)		2/18 (11.1%)
Paraesthesia oral	1/16 (6.3%)		0/18 (0%)
General disorders
Generalised oedema	1/16 (6.3%)		0/18 (0%)
Oedema	0/16 (0%)		2/18 (11.1%)
Hepatobiliary disorders
Drug-induced liver injury	1/16 (6.3%)		0/18 (0%)
Hypertransaminasaemia	0/16 (0%)		1/18 (5.6%)
Infections and infestations
Chronic hepatitis C	1/16 (6.3%)		0/18 (0%)
Pneumonia	0/16 (0%)		1/18 (5.6%)
Tooth abscess	1/16 (6.3%)		0/18 (0%)
Injury, poisoning and procedural complications
Limb injury	0/16 (0%)		1/18 (5.6%)
Investigations
Hepatic enzyme increased	7/16 (43.8%)		2/18 (11.1%)
Metabolism and nutrition disorders
Hyperuricaemia	1/16 (6.3%)		0/18 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/16 (6.3%)		0/18 (0%)
Nervous system disorders
Dizziness	0/16 (0%)		1/18 (5.6%)
Psychiatric disorders
Confusional state	1/16 (6.3%)		0/18 (0%)
Hallucination, visual	1/16 (6.3%)		0/18 (0%)
Reproductive system and breast disorders
Testicular swelling	1/16 (6.3%)		0/18 (0%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	0/16 (0%)		1/18 (5.6%)
Rash	1/16 (6.3%)		0/18 (0%)
Skin exfoliation	1/16 (6.3%)		0/18 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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