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

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

Detailed Description
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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

Official Title
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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

Conditions
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Complicated Urinary Tract Infection, Complicated Intra-abdominal Infection

Intervention / Treatment
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* Drug: Ceftazidime - Avibactam ( CAZ-AVI)
* Drug: Best Available Therapy
* Drug: Metronidazole


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftazidime - Avibactam ( CAZ-AVI)<br>IV treatment | Drug: Ceftazidime - Avibactam ( CAZ-AVI)<br>* 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<br>Drug: Metronidazole<br>* 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<br>* Other names: Flagyl;|
| Active Comparator: Best Available Therapy<br>IV treatment | Drug: Best Available Therapy<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response at Test of Cure (TOC) in Microbiological Modified Intent-to-treat (mMITT) Analysis Set | 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). | 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response at End of Treatment (EOT) in mMITT Analysis Set. | 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). | 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Clinical Response at Follow-up 1 (FU1) in mMITT Analysis Set | 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). | cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization | 
| Clinical Response at Follow-up 2 (FU2) in mMITT Analysis Set | 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). | At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization | 
| Clinical Response at EOT in Extended Microbiologically Evaluable (EME) at EOT Analysis Set. | Proportion of patients with clinical cure at the EOT visit in the EME at EOT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible). | 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Clinical Response at TOC in EME at TOC Analysis Set. | Proportion of patients with clinical cure at the TOC visit in the EME at TOC analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible). | 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days. | 
| Clinical Response at FU1 in EME at FU1 Analysis Set. | Proportion of patients with clinical cure at the FU1 visit in EME at FU1 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible). | cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization | 
| Clinical Response at FU2 in EME at FU2 Analysis Set | Proportion of patients with clinical cure at the FU2 visit in EME at FU2 analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary. | At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization | 
| Clinical Cure at TOC by Baseline Gram-negative Pathogen in mMITT Analysis Set | 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). | 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days. | 
| Clinical Cure at TOC by Baseline Gram-negative Pathogen in EME at TOC Analysis Set | 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). | 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days. | 
| Clinical Cure at TOC by Previously Failed Treatment Class in mMITT Analysis Set | 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). | 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Clinical Cure at EOT by Previously Failed Treatment Class in EME at EOT Analysis Set | 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). | 28 hours after completion of last infusion of study therapy.Duration of study therapy was 5 to 21 days. | 
| Clinical Cure at TOC by Previously Failed Treatment Class in EME at TOC Analysis Set | 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). | 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Clinical Cure at FU1 by Previously Failed Treatment Class in EME at FU1 Analysis Set | 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). | cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization | 
| Clinical Cure at FU2 by Previously Failed Treatment Class in EME at FU2 Analysis Set | 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. | At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization | 
| Per-patient Microbiological Response at EOT in mMITT Analysis Set | 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). | 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Per-patient Microbiological Response at TOC in mMITT Analysis Set | 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). | 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Per-patient Microbiological Response at FU1 in mMITT Analysis Set | 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). | cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization | 
| Per-patient Microbiological Response at FU2 in mMITT Analysis Set | 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). | At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization | 
| Per-patient Microbiological Response at EOT in EME at EOT Analysis Set | 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). | 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Per-patient Microbiological Response at TOC in EME at TOC Analysis Set | 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). | 6-12 days after last infusion of study therapy.Duration of study therapy was 5 to 21 days. | 
| Per-patient Microbiological Response at FU1 in EME at FU1 Analysis Set | 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). | cUTI: 20-27 calendar days from randomization/cIAI: 27-37 calendar days from randomization | 
| Per-patient Microbiological Response at FU2 in EME at FU2 Analysis Set | 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). | At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in mMITT Analysis Set | 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). | 28 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in mMITT Analysis Set | 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). | 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in mMITT Analysis Set | 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). | cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in mMITT Analysis Set | 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). | At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at EOT in EME at EOT Analysis Set | 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 hours after completion of last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC in EME at TOC Analysis Set | 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). | 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at FU1 in EME at FU1 Analysis Set | 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). | cIAI: 27-37 calendar days from randomization/cUTI: 20-27 calendar days from randomization | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at FU2 in EME at FU2 Analysis Set | 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). | At FU2, data was only collected for the cUTI Arms: 28-34 calendar days from randomization | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in mMITT Analysis Set | 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. | 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| Per-pathogen Microbiological Response of Gram-negative Pathogen at TOC by CAZ-AVI MIC in EME at TOC Analysis Set | 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. | 6-12 days after last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| The Reason for Treatment Change/Discontinuation in mMITT Analysis Set | Proportion of patients in the mMITT analysis set for whom the assigned study treatment was changed, discontinued, or interrupted. Creatinine clearance (CrCl) | From first infusion to last infusion of study therapy. Duration of study therapy was 5 to 21 days. | 
| The 28 Days All Cause Mortality Rate in mMITT Analysis Set | 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. | From first infusion to Day 28 | 
| The 28 Days All Cause Mortality Rate in EME at TOC Analysis Set | 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. | From first infusion to Day 28 | 
| Plasma Concentrations for Ceftazidime and Avibactam - cIAI in PK Analysis Set | Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration. | 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 | 
| Plasma Concentrations for Ceftazidime and Avibactam - cUTI in PK Analysis Set | Blood samples were taken on Day 3 for ceftazidime and avibactam plasma concentration. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ceftazidime,, avibactam,, metronidazone,, Anti-Infectives