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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01644643
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 345
• Locations: 46
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

To Evaluate the Effects of Ceftazidime-Avibactam and Best Available Therapy in patients with complicated urinary tract infections and complicated intra-abdominal infections.

Condition or Disease	Intervention/Treatment	Phase
Complicated Urinary Tract Infection; Complicated Intra-abdominal Infection	Drug: Ceftazidime - Avibactam ( CAZ-AVI); Drug: Best Available Therapy; Drug: Metronidazole	Phase 3

Detailed Description

An Open-Label, Randomized, Multicenter, Phase III Study of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) and Best Available Therapy for the Treatment of Infections Due to Ceftazidime Resistant Gram Negative Pathogens

Study Design

• Study Type: Interventional
• Actual Enrollment: 345 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Randomized, Multicenter, Phase III Study of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) and Best Available Therapy for the Treatment of Infections Due to Ceftazidime Resistant Gram Negative Pathogens
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ceftazidime - Avibactam ( CAZ-AVI) IV treatment	Drug: Ceftazidime - Avibactam ( CAZ-AVI); Ceftazidime 2000 mg and 500 mg of avibactam Patients randomized to receive CAZ-AVI will receive an infusion of CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 120 minutes; Drug: Metronidazole; Anti-infective, 500 mg (cIAI only) Patients randomized to receive CAZ-AVI for cIAI will also receive metronidazole (500 mg) administered by IV infusion in a volume of 100 mL at a constant rate over 60 minutes immediately following the CAZ-AVI infusion; Other Names: Flagyl
Active Comparator: Best Available Therapy IV treatment	Drug: Best Available Therapy; Patients randomized to receive Best Available Therapy will receive the best available standard of care (SOC) anti-infective therapy for their infection administered in accord with approved local label recommendation

Outcome Measures

Primary Outcome Measures

1. Clinical Response at Test of Cure (TOC) in Microbiological Modified Intent-to-treat (mMITT) Analysis Set [6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

Secondary Outcome Measures

1. Clinical Response at End of Treatment (EOT) in mMITT Analysis Set. [28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

2. Clinical Response at Follow-up 1 (FU1) in mMITT Analysis Set [cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization]

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

3. Clinical Response at Follow-up 2 (FU2) in mMITT Analysis Set [At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization]

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

4. Clinical Response at EOT in Extended Microbiologically Evaluable (EME) at EOT Analysis Set. [28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

5. Clinical Response at TOC in EME at TOC Analysis Set. [6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.]

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

6. Clinical Response at FU1 in EME at FU1 Analysis Set. [cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization]

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

7. Clinical Response at FU2 in EME at FU2 Analysis Set [At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization]

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

8. Clinical Cure at TOC by Baseline Gram-negative Pathogen in mMITT Analysis Set [6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.]

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

9. Clinical Cure at TOC by Baseline Gram-negative Pathogen in EME at TOC Analysis Set [6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.]

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

10. Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set [6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

11. Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set [28 hours after completion of last infusion of study therapy.Duration of study therapy was 5 to 21 days.]

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

12. Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set [6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

13. Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set [cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization]

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

14. Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set [At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization]

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

15. Per-patient Microbiological Response at EOT in mMITT Analysis Set [28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

16. Per-patient Microbiological Response at TOC in mMITT Analysis Set [6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

17. Per-patient Microbiological Response at FU1 in mMITT Analysis Set [cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization]

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

18. Per-patient Microbiological Response at FU2 in mMITT Analysis Set [At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization]

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

19. Per-patient Microbiological Response at EOT in EME at EOT Analysis Set [28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

20. Per-patient Microbiological Response at TOC in EME at TOC Analysis Set [6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.]

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

21. Per-patient Microbiological Response at FU1 in EME at FU1 Analysis Set [cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization]

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

22. Per-patient Microbiological Response at FU2 in EME at FU2 Analysis Set [At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization]

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

23. Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set [28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

24. Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set [6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

25. Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set [cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization]

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

26. Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set [At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization]

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

27. Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set [28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

28. Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set [6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

29. Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set [cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization]

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

30. Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set [At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization]

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

31. Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set [6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population). For E.coli, MIC available values are: <=0.008, 0.03, 0.06, 0.12, 0.25, 0.5, 1, 2, 8. For K. pneumoniae, MIC available values are: 0.06, 0.12, 0.25, 0.5, 1, 2, 4, 32, >32. For P. aeruginosa, MIC available values are: 2, 4, 8, 16, 32, >32.

32. Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set [6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

    Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population). For E.coli, MIC available values are: <=0.008, 0.03, 0.06, 0.12, 0.25, 0.5, 1, 2, 8. For K. pneumoniae, MIC available values are: 0.06, 0.12, 0.25, 0.5, 1, 2, 4, >32. For P. aeruginosa, MIC available values are: 2, 4, 8, 16, 32, >32.

33. The Reason for Treatment Change/Discontinuation in mMITT Analysis Set [From first infusion to last infusion of study therapy. Duration of study therapy was 5 to 21 days.]

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

34. The 28 Days All Cause Mortality Rate in mMITT Analysis Set [From first infusion to Day 28]

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

35. The 28 Days All Cause Mortality Rate in EME at TOC Analysis Set [From first infusion to Day 28]

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

36. Plasma Concentrations for Ceftazidime and Avibactam - cIAI in PK Analysis Set [Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 to 90 minutes after stopping study drug, anytime between 300 to 360 minutes after stopping study drug]

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

37. Plasma Concentrations for Ceftazidime and Avibactam - cUTI in PK Analysis Set [Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 to 90 minutes after stopping study drug, anytime between 300 to 360 minutes after stopping study drug]

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

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient must be ≥18 and ≤90 years of age

• Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after

• Patient has a ceftazidime-resistant Gram negative pathogen that was isolated from an appropriate culture within 5 days prior to study entry (ie, within 5 days prior to Screening; the study-qualifying culture), which was determined to be the causative agent of the entry infection

Exclusion Criteria:

• Patient has an APACHE II score >30 (cIAI patients only)

• Patient has an infection due to Gram negative pathogen that is unlikely to respond to CAZ-AVI treatment (eg, Acinetobacter spp., Stenotrophomonas spp.)

• Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant Patient is immunocompromised

• Patient has a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock such that they are unlikely to survive the 4- to 5-week study period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Shreveport	Louisiana	United States
2	Research Site	Lima	Ohio	United States
3	Research Site	El Talar		Argentina
4	Research Site	La Plata		Argentina
5	Research Site	Pazardzhik		Bulgaria
6	Research Site	Pleven		Bulgaria
7	Research Site	Ruse		Bulgaria
8	Research Site	Sofia		Bulgaria
9	Research Site	Varna		Bulgaria
10	Research Site	Veliko Turnovo		Bulgaria
11	Research Site	Slavonski Brod		Croatia
12	Research Site	Zagreb		Croatia
13	Research Site	Praha 5		Czechia
14	Research Site	Tours		France
15	Research Site	Nazareth		Israel
16	Research Site	Petach Tikva		Israel
17	Research Site	Ramat-Gan		Israel
18	Research Site	Tel Aviv		Israel
19	Research Site	Seoul		Korea, Republic of
20	Research Site	Guadalajara		Mexico
21	Research Site	Mexico, Distrito Federal		Mexico
22	Research Site	Cusco		Peru
23	Research Site	Surco		Peru
24	Research Site	Manila		Philippines
25	Research Site	Szczecin		Poland
26	Research Site	Bucharest		Romania
27	Research Site	Bucuresti		Romania
28	Research Site	Irkutsk		Russian Federation
29	Research Site	Krasnodar		Russian Federation
30	Research Site	Novosibirsk		Russian Federation
31	Research Site	Penza		Russian Federation
32	Research Site	Saint-Petersburg		Russian Federation
33	Research Site	St. Petersburg		Russian Federation
34	Research Site	St.-Petersburg,		Russian Federation
35	Research Site	Yaroslavl		Russian Federation
36	Research Site	Johannesburg		South Africa
37	Research Site	Barcelona		Spain
38	Research Site	Madrid		Spain
39	Research Site	Ankara		Turkey
40	Research Site	Antalya		Turkey
41	Research Site	Diyarbakir		Turkey
42	Research Site	Istanbul		Turkey
43	Research Site	Dnipropetrovsk		Ukraine
44	Research Site	Kharkiv		Ukraine
45	Research Site	Kyiv		Ukraine
46	Research Site	Zaporizhzhya		Ukraine

Sponsors and Collaborators

• Pfizer
• Forest Laboratories

Investigators

• Study Director: Paul Newell, MBBS, MRCP, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

• Carmeli Y, Armstrong J, Laud PJ, Newell P, Stone G, Wardman A, Gasink LB. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. Lancet Infect Dis. 2016 Jun;16(6):661-673. doi: 10.1016/S1473-3099(16)30004-4. Epub 2016 Apr 20.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01644643
• Other Study ID Numbers: D4280C00006; 2012-000726-21
• First Posted: Jul 19, 2012
• Last Update Posted: Sep 29, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Pfizer: Ceftazidime,; avibactam,; metronidazone,; Anti-Infectives
• Additional relevant MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections; Intraabdominal Infections; Metronidazole; Ceftazidime; Avibactam

Study Results

Participant Flow

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

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

Baseline Characteristics

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI	Total
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI: CAZ-AVI	Total of all reporting groups
Overall Participants	11	10	137	144	302
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.4 (11.12)	49.9 (16.14)	61.3 (15.33)	64.3 (14.64)	62.6 (15.12)
Age, Customized (Number) [Number]
18-45 Years	0 0%	3 30%	21 15.3%	19 13.2%	43 14.2%
46-64 Years	3 27.3%	5 50%	49 35.8%	41 28.5%	98 32.5%
65-74 Years	4 36.4%	2 20%	40 29.2%	46 31.9%	92 30.5%
75-90 Years	4 36.4%	0 0%	27 19.7%	38 26.4%	69 22.8%
Sex: Female, Male (Count of Participants)
Female	4 36.4%	6 60%	63 46%	64 44.4%	137 45.4%
Male	7 63.6%	4 40%	74 54%	80 55.6%	165 54.6%
Race/Ethnicity, Customized (Number) [Number]
Asian	0 0%	0 0%	1 0.7%	2 1.4%	3 1%
Black Or African American	0 0%	1 10%	1 0.7%	2 1.4%	4 1.3%
Other	0 0%	0 0%	4 2.9%	4 2.8%	8 2.6%
White	11 100%	9 90%	131 95.6%	136 94.4%	287 95%

Outcome Measures

1. Primary Outcome

Title	Clinical Response at Test of Cure (TOC) in Microbiological Modified Intent-to-treat (mMITT) Analysis Set
Description	Proportion of patients with clinical cure at the TOC visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Clinical cure	6	8	129	132
Clinical failure	0	0	2	2
Indeterminate	5	2	6	10

2. Secondary Outcome

Title	Clinical Response at End of Treatment (EOT) in mMITT Analysis Set.
Description	Proportion of patients with clinical cure at the EOT visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Clinical cure	6	9	136	142
Clinical failure	0	0	0	0
Indeterminate	5	1	1	2

3. Secondary Outcome

Title	Clinical Response at Follow-up 1 (FU1) in mMITT Analysis Set
Description	Proportion of patients with clinical cure at the FU1 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Clinical cure	6	8	121	127
Clinical failure	0	0	8	5
Indeterminate	5	2	8	12

4. Secondary Outcome

Title	Clinical Response at Follow-up 2 (FU2) in mMITT Analysis Set
Description	Proportion of patients with clinical cure at the FU2 visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	0	0	137	144
Clinical cure	118	123
Clinical failure	13	11
Indeterminate	6	10

5. Secondary Outcome

Title	Clinical Response at EOT in Extended Microbiologically Evaluable (EME) at EOT Analysis Set.
Description	Proportion of patients with clinical cure at the EOT visit in the EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended Microbiological Evaluable at EOT analysis set.

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	9	127	134
Clinical cure	5	9	127	134
Clinical failure	0	0	0	0

6. Secondary Outcome

Title	Clinical Response at TOC in EME at TOC Analysis Set.
Description	Proportion of patients with clinical cure at the TOC visit in the EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended Microbiological Evaluable at TOC analysis set.

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	8	122	128
Clinical cure	5	8	120	126
Clinical failure	0	0	2	2

7. Secondary Outcome

Title	Clinical Response at FU1 in EME at FU1 Analysis Set.
Description	Proportion of patients with clinical cure at the FU1 visit in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Extended Microbiological Evaluable at FU1 analysis set.

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	7	118	124
Clinical cure	5	7	110	120
Clinical failure	0	0	8	4

8. Secondary Outcome

Title	Clinical Response at FU2 in EME at FU2 Analysis Set
Description	Proportion of patients with clinical cure at the FU2 visit in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.
Time Frame	At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Extended Microbiological Evaluable at FU2 analysis set.

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	0	0	114	116
Clinical cure	102	106
Clinical failure	12	10

9. Secondary Outcome

Title	Clinical Cure at TOC by Baseline Gram-negative Pathogen in mMITT Analysis Set
Description	Proportion of patients with clinical cure at TOC visit by baseline pathogen (>=10% of frequency in the combined cIAI and cUTI patients) in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
E. coli - Clinical cure (n=6, 4, 57, 59)	2	3	54	53
K. pneumoniae - Clinical cure (n=3, 5, 65, 55)	2	3	61	54
P. aeruginosa - clinical cure (n=1, 1, 5, 14)	1	1	5	12

10. Secondary Outcome

Title	Clinical Cure at TOC by Baseline Gram-negative Pathogen in EME at TOC Analysis Set
Description	Proportion of patients with clinical cure at TOC visit by baseline Gram-negative pathogen (>=10% of frequency in the combined cIAI and cUTI patients) in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at TOC

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	8	124	131
E. coli - Clinical cure (n=2, 3, 48, 52)	2	3	47	51
K. pneumoniae - Clinical cure (n=2, 3, 59, 53)	2	3	59	53
P. aeruginosa - Clinical cure (n=1, 1, 5, 12)	1	1	5	12

11. Secondary Outcome

Title	Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set
Description	Proportion of patients with clinical cure at TOC visit by previously failed treatment class in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
At least 1 failed - Clin. cure (n=4,7,12,7)	3	7	12	6
Antibiotics - Clin. cure (n=0,1,0,0)	0	1	0	0
Carbapenems - Clin. cure (n=1,0,1,2)	0	0	1	1
Comb of Sulf/Trime inc Deriv-Clin. cure(n=0,0,2,0)	0	0	2	0
Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)	1	3	0	2
Cortico,Po. Comb W/Antibio.-Clin. cure(n=0,0,1,0)	0	0	1	0
First-Gen. Cephalosporins-Clin. cure (n=0,0,2,0)	0	0	2	0
Fluoroquinolones - Clin. cure (n=1,2,7,1)	0	2	7	1
Glycopeptide Antibacterials-Clin. cure (n=1,0,0,0)	0	0	0	0
Imidazole Derivatives - Clin. cure (n=2,3,0,0)	1	3	0	0
Other Aminoglycosides-Clin. cure (n=0,0,1,1)	0	0	1	1
Other Antibacterials-Clin. cure (n=0,1,1,0)	0	1	1	0
Other Antibio. F. Topic. Use-Clin. cure(n=0,0,1,0)	0	0	1	0
Penici. With Ext. Spectrum-Clin. cure(n=0,1,0,0)	0	1	0	0
Third-Gen.Cephalosporins -Clin. cure(n=2,4,3,2)	2	4	3	2

12. Secondary Outcome

Title	Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set
Description	Proportion of patients with clinical cure at EOT visit by previously failed treatment class in EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	28 hours after completion of last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at EOT

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	9	127	134
Antibiotics - Clin. cure (n=0,1,0,0)	0	1	0	0
Carbapenems - Clin. cure (n=0,0,1,1)	0	0	1	1
Comb of Sulf/Trime inc Deriv-Clin. cure(n=0,0,2,0)	0	0	2	0
Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)	1	3	0	2
Cortico,Po. Comb W/Antibio.-Clin. cure(n=0,0,1,0)	0	0	1	0
First-Gen. Cephalosporins-Clin. cure (n=0,0,2,0)	0	0	2	0
Fluoroquinolones - Clin. cure (n=0,2,5,1)	0	2	5	1
Imidazole Derivatives - Clin. cure (n=1,3,0,0)	1	3	0	0
Other Aminoglycosides-Clin. cure (n=0,0,1,1)	0	0	1	1
Other Antibacterials-Clin. cure (n=0,1,1,0)	0	1	1	0
Other Antibio. F. Topic. Use-Clin. cure(n=0,0,1,0)	0	0	1	0
Penici. With Ext. Spectrum-Clin. cure(n=0,1,0,0)	0	1	0	0
Third-Gen.Cephalosporins -Clin. cure(n=2,4,2,2)	2	4	2	2

13. Secondary Outcome

Title	Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set
Description	Proportion of patients with clinical cure at TOC visit by previously failed treatment class in EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at TOC

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	8	122	128
Antibiotics - Clin. cure (n=0,1,0,0)	0	1	0	0
Carbapenems - Clin. cure (n=0,0,1,1)	0	0	1	1
Comb of Sulf/Trime inc Deriv-Clin. cure(n=0,0,2,0)	0	0	2	0
Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)	1	3	0	2
Cortico,Po. Comb W/Antibio.-Clin. cure(n=0,0,1,0)	0	0	1	0
First-Gen. Cephalosporins-Clin. cure (n=0,0,2,0)	0	0	2	0
Fluoroquinolones - Clin. cure (n=0,2,5,1)	0	2	5	1
Imidazole Derivatives - Clin. cure (n=1,3,0,0)	1	3	0	0
Other Aminoglycosides-Clin. cure (n=0,0,0,1)	0	0	0	1
Other Antibacterials-Clin. cure (n=0,1,1,0)	0	1	1	0
Other Antibio. F. Topic. Use-Clin. cure(n=0,0,1,0)	0	0	1	0
Penici. With Ext. Spectrum-Clin. cure(n=0,1,0,0)	0	1	0	0
Third-Gen.Cephalosporins -Clin. cure(n=2,4,2,2)	2	4	2	2

14. Secondary Outcome

Title	Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set
Description	Proportion of patients with clinical cure at FU1 visit by previously failed treatment class in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
Time Frame	cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at FU1

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	7	118	124
Antibiotics - Clin. cure (n=0,1,0,0)	0	1	0	0
Carbapenems - Clin. cure (n=0,0,1,1)	0	0	1	1
Comb of Sulf/Trime inc Deriv-Clin. cure(n=0,0,1,0)	0	0	1	0
Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=1,3,0,2)	1	3	0	2
Cortico,Po. Comb W/Antibio.-Clin. cure(n=0,0,1,0)	0	0	0	0
First-Gen. Cephalosporins-Clin. cure (n=0,0,2,0)	0	0	2	0
Fluoroquinolones - Clin. cure (n=0,2,5,1)	0	2	4	1
Imidazole Derivatives - Clin. cure (n=1,3,0,0)	1	3	0	0
Other Aminoglycosides-Clin. cure (n=0,0,0,1)	0	0	0	1
Other Antibacterials-Clin. cure (n=0,1,1,0)	0	1	1	0
Other Antibio. F. Topic. Use-Clin. cure(n=0,0,1,0)	0	0	1	0
Penici. With Ext. Spectrum-Clin. cure(n=0,1,0,0)	0	1	0	0
Third-Gen.Cephalosporins -Clin. cure(n=2,4,1,2)	2	4	0	2

15. Secondary Outcome

Title	Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set
Description	Proportion of patients with clinical cure at FU2 visit by previously failed treatment class in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary.
Time Frame	At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at FU2

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	0	0	114	116
Carbapenems - Clin. cure (n=1,0)	0	0
Comb of Sulf/Trime inc Deriv-Clin. cure(n=1,0)	0	0
Combs Of Peni. Inc B-Lact. Inhib.-Cure(n=0,2)	0	2
Cortico,Po. Comb W/Antibio.-Clin. cure(n=1,0)	0	0
First-Gen. Cephalosporins-Clin. cure (n=2,0)	2	0
Fluoroquinolones - Clin. cure (n=5,0)	4	0
Other Aminoglycosides-Clin. cure (n=0,1)	0	1
Other Antibacterials-Clin. cure (n=1,0)	0	0
Other Antibio. F. Topic. Use-Clin. cure(n=1,0)	1	0
Third-Gen.Cephalosporins -Clin. cure(n=1,1)	0	1

16. Secondary Outcome

Title	Per-patient Microbiological Response at EOT in mMITT Analysis Set
Description	Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Favorable	6	9	130	136
Unfavorable	0	0	1	1
Indeterminate	5	1	6	7

17. Secondary Outcome

Title	Per-patient Microbiological Response at TOC in mMITT Analysis Set
Description	Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Favorable	6	8	88	118
Unfavorable	0	0	42	17
Indeterminate	5	2	7	9

18. Secondary Outcome

Title	Per-patient Microbiological Response at FU1 in mMITT Analysis Set
Description	Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Favorable	6	8	78	103
Unfavorable	0	0	50	29
Indeterminate	5	2	9	12

19. Secondary Outcome

Title	Per-patient Microbiological Response at FU2 in mMITT Analysis Set
Description	Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	0	0	137	144
Favorable	73	99
Unfavorable	54	35
Indeterminate	10	10

20. Secondary Outcome

Title	Per-patient Microbiological Response at EOT in EME at EOT Analysis Set
Description	Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at EOT

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	9	127	134
Favorable	5	9	127	133
Unfavorable	0	0	0	1

21. Secondary Outcome

Title	Per-patient Microbiological Response at TOC in EME at TOC Analysis Set
Description	Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at TOC

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	8	124	131
Favorable	5	8	84	114
Unfavorable	0	0	40	17

22. Secondary Outcome

Title	Per-patient Microbiological Response at FU1 in EME at FU1 Analysis Set
Description	Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at FU1

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	7	120	126
Favorable	5	7	75	98
Unfavorable	0	0	45	28

23. Secondary Outcome

Title	Per-patient Microbiological Response at FU2 in EME at FU2 Analysis Set
Description	Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cIAI patients where the clinical response was changed to indeterminate due to a Surgical Review Panel assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at FU2

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	0	0	115	117
Favorable	68	85
Unfavorable	47	32

24. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame	28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Escherichia coli - Favorable (n=6, 4, 57, 59)	2	3	53	57
Escherichia coli - Unfavorable (n=6, 4, 57, 59)	0	0	0	0
Escherichia coli - Indeterminate (n=6, 4, 57, 59)	4	1	4	2
Kleb. pneumoniae - Favorable (n=3, 5, 65, 55)	2	4	61	52
Kleb. pneumoniae - Unfavorable (n=3, 5, 65, 55)	0	0	1	0
Kleb. pneumoniae - Indeterminate (n=3, 5, 65, 55)	1	1	3	3
Pseudo. aeruginosa - Favorable (n=1, 1, 5, 14)	1	1	5	14
Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 14)	0	0	0	0
Pseudo. aeruginosa - Indeterminate (n=1, 1, 5, 14)	0	0	0	0

25. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame	6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Escherichia coli - Favorable (n=6, 4, 57, 59)	2	3	38	52
Escherichia coli - Unfavorable (n=6, 4, 57, 59)	0	0	16	3
Escherichia coli - Indeterminate (n=6, 4, 57, 59)	4	1	3	4
Kleb. pneumoniae - Favorable (n=3, 5, 65, 55)	2	3	43	46
Kleb. pneumoniae - Unfavorable (n=3, 5, 65, 55)	0	0	19	8
Kleb. pneumoniae - Indeterminate (n=3, 5, 65, 55)	1	2	3	1
Pseudo. aeruginosa - Favorable (n=1, 1, 5, 14)	1	1	3	11
Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 14)	0	0	2	2
Pseudo. aeruginosa - Indeterminate (n=1, 1, 5, 14)	0	0	0	1

26. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequency in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame	cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Escherichia coli - Favorable (n=6, 4, 57, 59)	2	3	33	45
Escherichia coli - Unfavorable (n=6, 4, 57, 59)	0	0	18	12
Escherichia coli - Indeterminate (n=6, 4, 57, 59)	4	1	6	2
Kleb. pneumoniae - Favorable (n=3, 5, 65, 55)	2	3	39	42
Kleb. pneumoniae - Unfavorable (n=3, 5, 65, 55)	0	0	23	10
Kleb. pneumoniae - Indeterminate (n=3, 5, 65, 55)	1	2	3	3
Pseudo. aeruginosa - Favorable (n=1, 1, 5, 14)	1	1	3	8
Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 14)	0	0	2	2
Pseudo. aeruginosa - Indeterminate (n=1, 1, 5, 14)	0	0	0	4

27. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame	At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	0	0	137	144
Escherichia coli - Favorable (n=0, 0, 57, 59)	32	43
Escherichia coli - Unfavorable (n=0, 0, 57, 59)	19	14
Escherichia coli - Indeterminate (n=0, 0, 57, 59)	6	2
Kleb. pneumoniae - Favorable (n=0, 0, 65, 55)	35	39
Kleb. pneumoniae - Unfavorable (n=0, 0, 65, 55)	26	14
Kleb. pneumoniae - Indeterminate (n=0, 0, 65, 55)	4	2
Pseudo. aeruginosa - Favorable (n=0, 0, 5, 14)	2	10
Pseudo. aeruginosa - Unfavorable (n=0, 0, 5, 14)	3	2
Pseudo. aeruginosa - Indeterminate (n=0, 0, 5, 14)	0	2

28. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame	28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at EOT

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	9	127	134
Escherichia coli - Favorable (n=2, 3, 51, 55)	2	3	51	55
Escherichia coli - Unfavorable (n=2, 3, 51, 55)	0	0	0	0
Kleb. pneumoniae - Favorable (n=2, 4, 60, 52)	2	4	60	52
Kleb. pneumoniae - Unfavorable (n=2, 4, 60, 52)	0	0	0	0
Pseudo. aeruginosa - Favorable (n=1, 1, 5, 14)	1	1	5	14
Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 14)	0	0	0	0

29. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame	6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at TOC

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	8	124	131
Escherichia coli - Favorable (n=2, 3, 49, 53)	2	3	34	50
Escherichia coli - Unfavorable (n=2, 3, 49, 53)	0	0	15	3
Kleb. pneumoniae - Favorable (n=2, 3, 60, 53)	2	3	42	45
Kleb. pneumoniae - Unfavorable (n=2, 3, 60, 53)	0	0	18	8
Pseudo. aeruginosa - Favorable (n=1, 1, 5, 13)	1	1	3	11
Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 13)	0	0	2	2

30. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame	cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at FU1

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	7	120	126
Escherichia coli - Favorable (n=2, 3, 46, 54)	2	3	30	43
Escherichia coli - Unfavorable (n=2, 3, 46, 54)	0	0	16	11
Kleb. pneumoniae - Favorable (n=2, 2, 59, 50)	2	2	38	40
Kleb. pneumoniae - Unfavorable (n=2, 2, 59, 50)	0	0	21	10
Pseudo. aeruginosa - Favorable (n=1, 1, 5, 10)	1	1	3	8
Pseudo. aeruginosa - Unfavorable (n=1, 1, 5, 10)	0	0	2	2

31. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population).
Time Frame	At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at FU2

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	0	0	115	117
Escherichia coli - Favorable (n=44, 50)	28	39
Escherichia coli - Unfavorable (n=44, 50)	16	11
Kleb. pneumoniae - Favorable (n= 56, 46)	33	32
Kleb. pneumoniae - Unfavorable (n=56, 46)	23	14
Pseudo. aeruginosa - Favorable (n=4, 11)	2	9
Pseudo. aeruginosa - Unfavorable (n=4, 11)	2	2

32. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population). For E.coli, MIC available values are: <=0.008, 0.03, 0.06, 0.12, 0.25, 0.5, 1, 2, 8. For K. pneumoniae, MIC available values are: 0.06, 0.12, 0.25, 0.5, 1, 2, 4, 32, >32. For P. aeruginosa, MIC available values are: 2, 4, 8, 16, 32, >32.
Time Frame	6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
E. coli (MIC: <=0.008) - Favorable (n=0, 0, 1, 1)	0	0	1	1
E. coli (MIC: 0.03) - Favorable (n=0, 0, 0, 2)	0	0	0	1
E. coli (MIC: 0.06) - Favorable (n=1, 0, 3, 2)	0	0	3	2
E. coli (MIC: 0.12) - Favorable (n=4, 2, 20, 20)	2	1	12	16
E. coli (MIC: 0.25) - Favorable (n=0, 0, 15, 16)	0	0	10	15
E. coli (MIC: 0.5) - Favorable (n=0, 1, 8, 11)	0	1	5	10
E. coli (MIC: 1) - Favorable (n=0, 0, 2, 2)	0	0	1	2
E. coli (MIC: 2) - Favorable (n=0, 0, 2, 1)	0	0	2	1
E. coli (MIC: 8) - Favorable (n=0, 0, 2, 4)	0	0	2	4
K. pneumoniae (MIC: 0.06) - Favorable (n=0,0,2,0)	0	0	1	0
K. pneumoniae (MIC: 0.12) - Favorable (n=0,1,8,5)	0	0	6	4
K. pneumoniae (MIC: 0.25) - Favorable (n=0,3,12,6)	0	2	7	5
K. pneumoniae (MIC: 0.5) - Favorable (n=2,0,24,22)	1	0	16	19
K. pneumoniae (MIC: 1) - Favorable (n=0,0,16,18)	0	0	11	16
K. pneumoniae (MIC: 2) - Favorable (n=1, 1, 1, 2)	1	1	1	1
K. pneumoniae (MIC: 4) - Favorable (n=0, 0, 1, 1)	0	0	1	0
K. pneumoniae (MIC: 32) - Favorable (n=0, 0, 1, 0)	0	0	0	0
K. pneumoniae (MIC: >32) - Favorable (n=0,0,0,1)	0	0	0	0
P. aeruginosa (MIC: 2) - Favorable (n=1, 0, 0, 1)	1	0	0	1
P. aeruginosa (MIC: 4) - Favorable (n=0, 0, 3, 2)	0	0	1	1
P. aeruginosa (MIC: 8) - Favorable (n=0, 0, 0, 2)	0	0	0	2
P. aeruginosa (MIC: 16) - Favorable (n=0, 1, 0, 1)	0	1	0	0
P. aeruginosa (MIC: 32) - Favorable (n=0, 0, 1, 3)	0	0	1	3
P. aeruginosa (MIC: >32) - Favorable (n=0,0,1,5)	0	0	1	4

33. Secondary Outcome

Title	Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set
Description	Proportion of patients with a favorable per-pathogen microbiological response for pathogens (>=10% of frequncy in the combined cIAI and cUTI patients): favourable microbiological response includes: Eradication Absence (or urine quantification less than 10^4 CFU/ml for cUTI patients) of causative pathogen from an appropriately obtained specimen at the site of infection. If the patient was bacteremic at Screening, the bacteremia has also resolved. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure (specific to cIAI population). For E.coli, MIC available values are: <=0.008, 0.03, 0.06, 0.12, 0.25, 0.5, 1, 2, 8. For K. pneumoniae, MIC available values are: 0.06, 0.12, 0.25, 0.5, 1, 2, 4, >32. For P. aeruginosa, MIC available values are: 2, 4, 8, 16, 32, >32.
Time Frame	6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at TOC

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	8	124	131
E. coli (MIC: <=0.008) - Favorable (n=0, 0, 1, 1)	0	0	1	1
E. coli (MIC: 0.03) - Favorable (n=0, 0, 0, 2)	0	0	0	1
E. coli (MIC: 0.06) - Favorable (n=0, 0, 3, 1)	0	0	3	1
E. coli (MIC: 0.12) - Favorable (n=2, 1, 18, 18)	2	1	10	16
E. coli (MIC: 0.25) - Favorable (n=0, 0, 13, 15)	0	0	9	15
E. coli (MIC: 0.5) - Favorable (n=0, 1, 6, 9)	0	1	4	9
E. coli (MIC: 1) - Favorable (n=0, 0, 2, 2)	0	0	1	2
E. coli (MIC: 2) - Favorable (n=0, 0, 2, 1)	0	0	2	1
E. coli (MIC: 8) - Favorable (n=0, 0, 2, 4)	0	0	2	4
K. pneumoniae (MIC: 0.06) - Favorable (n=0,0,1,0)	0	0	0	0
K. pneumoniae (MIC: 0.12) - Favorable (n=0,0,8,5)	0	0	6	4
K. pneumoniae (MIC: 0.25) - Favorable (n=0,2,11,6)	0	2	7	5
K. pneumoniae (MIC: 0.5) - Favorable (n=1,0,23,21)	1	0	16	19
K. pneumoniae (MIC: 1) - Favorable (n=0,0,15,17)	0	0	11	15
K. pneumoniae (MIC: 2) - Favorable (n=1, 1, 1, 2)	1	1	1	2
K. pneumoniae (MIC: 4) - Favorable (n=0, 0, 1, 1)	0	0	1	0
K. pneumoniae (MIC: >32) - Favorable (n=0,0,0,1)	0	0	0	0
P. aeruginosa (MIC: 2) - Favorable (n=1, 0, 0, 1)	1	0	0	1
P. aeruginosa (MIC: 4) - Favorable (n=0, 0, 3, 2)	0	0	1	1
P. aeruginosa (MIC: 8) - Favorable (n=0, 0, 0, 2)	0	0	0	2
P. aeruginosa (MIC: 16) - Favorable (n=0, 1, 0, 1)	0	1	0	0
P. aeruginosa (MIC: 32) - Favorable (n=0, 0, 1, 3)	0	0	1	3
P. aeruginosa (MIC: >32) - Favorable (n=0,0,1,4)	0	0	1	4

34. Secondary Outcome

Title	The Reason for Treatment Change/Discontinuation in mMITT Analysis Set
Description	Proportion of patients in the mMITT analysis set for whom the assigned study treatment was changed, discontinued, or interrupted. Creatinine clearance (CrCl)
Time Frame	From first infusion to last infusion of study therapy. Duration of study therapy was 5 to 21 days.

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
Treatment Change	1	0	8	11
Treatment Change - Crcl change	1	0	5	10
Treatment Change - Other	0	0	3	1
Treatment discontinuation	4	0	3	1
Treatment discontinuation - AE	1	0	1	1
Treatment discontinuation - Other	3	0	2	0
Treatment interrupted	0	0	0	1
Treatment interrupted - Change of infusion site	0	0	0	1

35. Secondary Outcome

Title	The 28 Days All Cause Mortality Rate in mMITT Analysis Set
Description	Proportion of patients with Day 28 all-cause mortality in mMITT analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.
Time Frame	From first infusion to Day 28

Outcome Measure Data

Analysis Population Description

Microbiological modified intent to treat

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	11	10	137	144
All cause mortality	1	0	3	3
Deaths due to disease progression	0	0	0	0
Number of patients with any AE with outcome=death	1	0	3	3

36. Secondary Outcome

Title	The 28 Days All Cause Mortality Rate in EME at TOC Analysis Set
Description	Proportion of patients with Day 28 all-cause mortality in EME at TOC analysis set. The death in the cIAI patient were reviewed independently by the SRP Chair.
Time Frame	From first infusion to Day 28

Outcome Measure Data

Analysis Population Description

Extended microbiologically evaluable at TOC

Arm/Group Title	cIAI:Best Available Therapy	cIAI:CAZ-AVI + Metronidazole	cUTI:Best Available Therapy	cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator	cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)	cUTI:Best Available Therapy Determinated by Investigator	cUTI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)
Measure Participants	5	8	124	131
All cause mortality	0	0	1	1
Deaths due to disease progression	0	0	0	0
Number of patients with any AE withoutcome=death	0	0	1	1

37. Secondary Outcome

Title	Plasma Concentrations for Ceftazidime and Avibactam - cIAI in PK Analysis Set
Description	Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.
Time Frame	Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 to 90 minutes after stopping study drug, anytime between 300 to 360 minutes after stopping study drug

Outcome Measure Data

Analysis Population Description

PK Analysis set

Arm/Group Title	CAZ (1)	AVI (1)	CAZ (2)	AVI (2)	CAZ (3)	AVI (3)
Arm/Group Description	15 mins before/after dose	15 mins before/after dose	30-90 mins after dose	30-90 mins after dose	300-360 mins after dose	300-360 mins after dose
Measure Participants	12	12	12	12	12	12
Geometric Mean (Full Range) [NG/ML]	23880.3	3061.3	39465.3	6304.1	14904.8	1769.3

38. Secondary Outcome

Title	Plasma Concentrations for Ceftazidime and Avibactam - cUTI in PK Analysis Set
Description	Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration.
Time Frame	Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 to 90 minutes after stopping study drug, anytime between 300 to 360 minutes after stopping study drug

Outcome Measure Data

Analysis Population Description

PK Analysis set

Arm/Group Title	CAZ (1)	AVI (1)	CAZ (2)	AVI (2)	CAZ (3)	AVI (3)
Arm/Group Description	15 mins before/after dose	15 mins before/after dose	30-90 mins after dose	30-90 mins after dose	300-360 mins after dose	300-360 mins after dose
Measure Participants	145	147	141	147	146	146
Geometric Mean (Full Range) [NG/ML]	74260.2	10103.8	56905.9	8141.2	21442.0	2425.0

Adverse Events

Time Frame	Non serious AEs and SAEs were from the first infusion of study therapy through the FU visits (cIAI: 28-35 days calendar days from randomization, cUTI: 28-32 calendar days from randomization).
Adverse Event Reporting Description	One participant in the "cUTI:CAZ-AVI" arm was randomized but did not receive study drug. This participant was not included in the safety analysis."
Arm/Group Title	cIAI:Best Available Therapy		cIAI:CAZ-AVI + Metronidazole		cUTI:Best Available Therapy		cUTI:CAZ-AVI
Arm/Group Description	cIAI: Best Available Therapy Determinated by Investigator		cIAI:CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) plus metronidazole (500 mg)		cUTI:Best Available Therapy Determinated by Investigator		cUTI: CAZ-AVI
All Cause Mortality
	cIAI:Best Available Therapy		cIAI:CAZ-AVI + Metronidazole		cUTI:Best Available Therapy		cUTI:CAZ-AVI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	cIAI:Best Available Therapy		cIAI:CAZ-AVI + Metronidazole		cUTI:Best Available Therapy		cUTI:CAZ-AVI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/15 (33.3%)		2/12 (16.7%)		5/153 (3.3%)		7/152 (4.6%)
Cardiac disorders
Cardiac arrest	0/15 (0%)	0	0/12 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Cardio-respiratory arrest	0/15 (0%)	0	0/12 (0%)	0	2/153 (1.3%)	2	1/152 (0.7%)	1
Gastrointestinal disorders
Intestinal obstruction	0/15 (0%)	0	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Hernial eventration	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Nausea	0/15 (0%)	0	0/12 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Small intestinal perforation	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
General disorders
Asthenia	0/15 (0%)	0	0/12 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Infections and infestations
Urosepsis	0/15 (0%)	0	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Lobar pneumonia	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Pneumonia	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Urinary tract infection enterococcal	0/15 (0%)	0	0/12 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Injury, poisoning and procedural complications
Pancreatic injury	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Post procedural fistula	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/15 (0%)	0	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/15 (0%)	0	0/12 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Nervous system disorders
Presyncope	0/15 (0%)	0	0/12 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Renal and urinary disorders
Renal failure	0/15 (0%)	0	0/12 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/15 (0%)	0	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Pneumonia aspiration	0/15 (0%)	0	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Pulmonary embolism	0/15 (0%)	0	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Respiratory failure	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Vascular disorders
Deep vein thrombosis	0/15 (0%)	0	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Other (Not Including Serious) Adverse Events
	cIAI:Best Available Therapy		cIAI:CAZ-AVI + Metronidazole		cUTI:Best Available Therapy		cUTI:CAZ-AVI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/15 (80%)		8/12 (66.7%)		36/153 (23.5%)		18/152 (11.8%)
Blood and lymphatic system disorders
Anaemia	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Cardiac disorders
Angina pectoris	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Arrhythmia supraventricular	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Cardiovascular insufficiency	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Palpitations	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Supraventricular tachycardia	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Ear and labyrinth disorders
Tinnitus	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/15 (6.7%)	4	0/12 (0%)	0	4/153 (2.6%)	5	3/152 (2%)	3
Constipation	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	2/152 (1.3%)	2
Diarrhoea	0/15 (0%)	0	2/12 (16.7%)	2	8/153 (5.2%)	8	3/152 (2%)	4
Duodenitis	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Dyspepsia	0/15 (0%)	0	0/12 (0%)	0	5/153 (3.3%)	5	2/152 (1.3%)	2
Enteritis	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Oesophagitis	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Pancreatitis acute	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Gastritis	1/15 (6.7%)	1	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Gastritis erosive	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Nausea	1/15 (6.7%)	1	3/12 (25%)	3	9/153 (5.9%)	9	5/152 (3.3%)	5
Vomiting	1/15 (6.7%)	1	2/12 (16.7%)	2	2/153 (1.3%)	2	4/152 (2.6%)	5
General disorders
Catheter site haemorrhage	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Hyperthermia	1/15 (6.7%)	1	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Pyrexia	0/15 (0%)	0	0/12 (0%)	0	2/153 (1.3%)	3	4/152 (2.6%)	8
Infections and infestations
Incision site infection	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Oral herpes	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Orchitis	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Respiratory tract infection viral	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Injury, poisoning and procedural complications
Gastrointestinal stoma complication	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Procedural pain	1/15 (6.7%)	1	0/12 (0%)	0	2/153 (1.3%)	3	0/152 (0%)	0
Investigations
Electrocardiogram QT prolonged	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Endoscopy gastrointestinal abnormal	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Weight decreased	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/15 (0%)	0	1/12 (8.3%)	1	1/153 (0.7%)	1	0/152 (0%)	0
Metabolic acidosis	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Type 2 diabetes mellitus	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/15 (6.7%)	1	1/12 (8.3%)	1	1/153 (0.7%)	1	1/152 (0.7%)	1
Back pain	0/15 (0%)	0	2/12 (16.7%)	2	0/153 (0%)	0	0/152 (0%)	0
Muscular weakness	1/15 (6.7%)	1	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Bone pain	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Myalgia	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	2/152 (1.3%)	2
Neck pain	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Nervous system disorders
Hydrocephalus	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Parosmia	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Dizziness	0/15 (0%)	0	1/12 (8.3%)	1	1/153 (0.7%)	1	1/152 (0.7%)	1
Headache	1/15 (6.7%)	1	2/12 (16.7%)	2	11/153 (7.2%)	17	1/152 (0.7%)	1
Paraesthesia	0/15 (0%)	0	2/12 (16.7%)	2	0/153 (0%)	0	0/152 (0%)	0
Psychiatric disorders
Depression	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Insomnia	4/15 (26.7%)	4	2/12 (16.7%)	2	0/153 (0%)	0	2/152 (1.3%)	2
Renal and urinary disorders
Nocturia	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/15 (0%)	0	2/12 (16.7%)	2	0/153 (0%)	0	1/152 (0.7%)	1
Pulmonary fibrosis	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Atelectasis	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Hydrothorax	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Oropharyngeal pain	1/15 (6.7%)	1	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Respiratory failure	1/15 (6.7%)	1	0/12 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Rhinorrhoea	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Tachypnoea	1/15 (6.7%)	1	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	1/15 (6.7%)	1	1/12 (8.3%)	1	1/153 (0.7%)	1	0/152 (0%)	0
Hyperhidrosis	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Skin ulcer	0/15 (0%)	0	1/12 (8.3%)	1	0/153 (0%)	0	0/152 (0%)	0
Pruritus	0/15 (0%)	0	1/12 (8.3%)	1	1/153 (0.7%)	1	2/152 (1.3%)	2
Rash	0/15 (0%)	0	1/12 (8.3%)	1	1/153 (0.7%)	1	0/152 (0%)	0
Urticaria	1/15 (6.7%)	1	0/12 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Vascular disorders
Phlebitis	1/15 (6.7%)	2	2/12 (16.7%)	2	2/153 (1.3%)	2	1/152 (0.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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