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

Complicated Urinary Tract Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01644643
• Other study ID #: D4280C00006
• Secondary ID: 2012-000726-21
• Status: Completed
• Phase: Phase 3
• First received: June 28, 2012
• Last updated: August 31, 2017
• Start date: January 2013
• Est. completion date: September 2014

Study information

• Verified date: August 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 345
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Complicated Intra-abdominal Infection
• Complicated Urinary Tract Infection
• Infection
• Intraabdominal Infections
• Urinary Tract Infections

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Argentina	Research Site	El Talar
Argentina	Research Site	La Plata
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Veliko Turnovo
Croatia	Research Site	Slavonski Brod
Croatia	Research Site	Zagreb
Czechia	Research Site	Praha 5
France	Research Site	Tours
Israel	Research Site	Nazareth
Israel	Research Site	Petach Tikva
Israel	Research Site	Ramat-Gan
Israel	Research Site	Tel Aviv
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico, Distrito Federal
Peru	Research Site	Cusco
Peru	Research Site	Surco
Philippines	Research Site	Manila
Poland	Research Site	Szczecin
Romania	Research Site	Bucharest
Romania	Research Site	Bucuresti
Russian Federation	Research Site	Irkutsk
Russian Federation	Research Site	Krasnodar
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St.-Petersburg,
Russian Federation	Research Site	Yaroslavl
South Africa	Research Site	Johannesburg
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Diyarbakir
Turkey	Research Site	Istanbul
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Zaporizhzhya
United States	Research Site	Lima	Ohio
United States	Research Site	Shreveport	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Forest Laboratories

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Croatia,  Czechia,  France,  Israel,  Korea, Republic of,  Mexico,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Turkey,  Ukraine, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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