This study is designed to provide evidence of efficacy of cefiderocol in the treatment of serious infections in adult patients caused by carbapenem-resistant Gram-negative pathogens.
This study is designed to provide evidence of efficacy of cefiderocol in the treatment of serious infections in adult patients with either hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), healthcare-associated pneumonia (HCAP), complicated urinary tract infection (cUTI), or bloodstream infections (BSI)/sepsis caused by carbapenem-resistant Gram-negative pathogens.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
152
2 g intravenously over 3 hours every 8 hours for a period of 7 to 14 days, or 2 g every 6 hours for participants with creatinine clearance \>120 mL/min.
Standard of care with either a polymyxin-based or non-polymyxin-based regimen as determined by the investigator and consisting of one to three marketed antibacterial agent(s).
Shionogi Research Site
Hartford, Connecticut, United States
Shionogi Research Site
Newark, Delaware, United States
Shionogi Research Site
Chicago, Illinois, United States
Shionogi Research Site
New Orleans, Louisiana, United States
Shionogi Research Site
Detroit, Michigan, United States
Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. Participants with missing data were considered as non-responders.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Microbiologic Eradication at TOC in Participants With cUTI
Microbiological outcome per Baseline pathogen was determined by the sponsor as defined for each infection site. For cUTI eradication was defined as a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ colony-forming units (CFU)/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after the end of treatment, equivalent to Study Days 14 to 21
Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy was required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy was required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Clinical Cure at Test of Cure in Participants With cUTI
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With cUTI
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With cUTI
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy is required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy is required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC. cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis: HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy was required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy was required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC. cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis: HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis: HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy was required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy was required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC. cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria established for each infection site: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen (sputum, tracheal aspirate, bronchoalveolar lavage (BAL) fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria established for each infection site: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen (sputum, tracheal aspirate, bronchoalveolar lavage (BAL) fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis
Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. If an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For sepsis, if the participant has a successful clinical outcome after TOC and an appropriate clinical culture could not be obtained, the response was presumed sustained eradication. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Microbiologic Eradication at EOT in Participants With cUTI
Microbiological outcome per Baseline pathogen was determined by the sponsor as defined for each infection site. For cUTI eradication was defined as a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With cUTI
Microbiological outcome per Baseline pathogen at follow-up was determined by the sponsor as defined for each infection site. For cUTI sustained eradication was defined as a culture taken any time after documented eradication at TOC and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained \<10³ CFU/mL. Overall per-participant sustained eradication was defined as sustained eradication of all Baseline Gram-negative pathogens.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained \< 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen
Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained \< 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen
Microbiological outcome per Baseline carbapenem-resistant pathogen were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen
Microbiological outcome per Baseline carbapenem-resistant pathogen were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen
Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained \< 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With Microbiologic Eradication at EOT in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia
The percentage of participants who experienced eradication of the Baseline documented carbapenem-resistant Gram-negative bacteremia, defined as absence of the Baseline Gram-negative pathogen from a blood culture.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With Microbiologic Eradication at TOC in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia
The percentage of participants who experienced eradication of the Baseline documented carbapenem-resistant Gram-negative bacteremia, defined as absence of the Baseline Gram-negative pathogen from a blood culture.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia
The percentage of participants who experienced sustained eradication of the Baseline documented carbapenem-resistant Gram-negative bacteremia, defined as absence of the Baseline Gram-negative pathogen from a blood culture after TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Percentage of Participants With a Composite Clinical and Microbiological Response at EOT
The composite clinical and microbiological response rate is defined as the percentage of participants with both clinical cure and microbiologic eradication, as defined above for each site of infection.
Time frame: End of treatment, Day 7 to 14
Percentage of Participants With a Composite Clinical and Microbiological Response at TOC
The composite clinical and microbiological response rate is defined as the percentage of participants with both clinical cure and microbiologic eradication, as defined above for each site of infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up
The composite clinical and microbiological response rate is defined as the percentage of participants with both sustained clinical cure and sustained microbiologic eradication, as defined above for each site of infection.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
All-cause Mortality at Day 14 and Day 28
The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants who experienced mortality regardless of the cause at or before Day 14 and Day 28, respectively.
Time frame: Day 14 and Day 28
Percentage of Participants Alive and With No Change in Antibiotic Treatment Due to Either Lack of Therapeutic Benefit or Drug-related Toxicity at TOC
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Survival Time
Survival time was analyzed by Kaplan-Meier survival curve. The table below presents deaths that occurred in10-day time intervals through the end of study
Time frame: Days 1 to 10, 11 to 20, 21 to 30, 31 to 40, 41-50, and 51 to 60.
Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP)
Clinical pulmonary infection score (CPIS) is a surrogate for diagnosis and treatment response. Points (0, 1, or 2) are assigned for observed findings for 5 variables including body temperature, white blood cell count, tracheal secretions, ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), and chest radiograph infiltrates. The total score ranges from 0 to 10, where higher scores may indicate a higher likelihood of mortality; a negative change from Baseline indicates improvement
Time frame: Baseline, end of treatment (Day 7-14), test of cure (7 days after end of treatment, equivalent to Study Day 14 to 21) and follow-up (14 days after end of treatment, equivalent to Study Day 21 to 28)
Change From Baseline in Sequential Organ Failure Assessment (SOFA)
The SOFA score is a scoring system to determine the extent of a patient's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each score is from 0 to 4, and the total score ranges from 0 to 24, where higher scores indicate a higher likelihood of mortality. A negative change from Baseline score indicates improvement.
Time frame: Baseline, end of treatment (Day 7 to 14), test of cure (7 days after end of treatment, equivalent to Study Day 14 to 21) and follow-up (14 days after end of treatment, equivalent to Study Day 21 to 28)
Number of Participants With Adverse Events
The severity of each adverse event (AE) was graded by the investigator according to the following definitions: * Mild: Symptom or finding is minor and does not interfere with usual daily activities * Moderate: The event causes discomfort and interferes with usual daily activity or affects clinical status * Severe: The event causes interruption of usual daily activities or has a clinically significant effect The relationship of AEs to study treatment was determined by the investigator according to the following definition: ● Related: An AE which can be reasonably explained as having been caused by the study treatment. A serious AE is defined as any AE that resulted in any of the following outcomes: * Death * Life-threatening condition * Hospitalization or prolongation of existing hospitalization * Persistent or significant disability/incapacity * Congenital anomaly/birth defect * Other medically important condition
Time frame: From first dose of study drug up to 28 days after last dose; maximum treatment duration was 29 days in the cefiderocol group and 22 days in the BAT group.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Shionogi Research Site
Pittsburgh, Pennsylvania, United States
Shionogi Research Site
Salvador, Estado de Bahia, Brazil
Shionogi Research Site
Curitiba, Paraná, Brazil
Shionogi Research Site
Passo Fundo, Rio Grande do Sul, Brazil
Shionogi Research Site
Porto Alegre, Rio Grande do Sul, Brazil
...and 75 more locations