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

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).

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).

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).

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).

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).

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).

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).

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.

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).

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).

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).

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).

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).

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).

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.

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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.

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.

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

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.

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.

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

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