CREDIBLE - CR: Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens

• Sponsor: Shionogi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02714595
• Collaborator: (none)
• Enrollment: 152
• Locations: 85
• Arms: 2
• Actual Duration (Months): 31.4
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthcare-associated Pneumonia (HCAP); Bloodstream Infections (BSI); Hospital Acquired Pneumonia (HAP); Complicated Urinary Tract Infection (cUTI); Sepsis; Ventilator Associated Pneumonia (VAP)	Drug: Cefiderocol; Drug: Best Available Therapy	Phase 3

Detailed Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Open-label Clinical Study of S-649266 or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens
• Actual Study Start Date: Sep 7, 2016
• Actual Primary Completion Date: Apr 1, 2019
• Actual Study Completion Date: Apr 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cefiderocol Participants will receive cefiderocol 2 g administered intravenously over 3 hours, every 8 hours for 7-14 days. Treatment could be extended to 21 days at the discretion of the investigator.	Drug: Cefiderocol; 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.; Other Names: S-649266 Fetroja ®
Active Comparator: Best Available Therapy (BAT) Best available therapy (BAT) will be chosen by the investigator and may include up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days. Treatment could be extended to 21 days at the discretion of the investigator.	Drug: Best Available Therapy; 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).

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

   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.

2. Percentage of Participants With Microbiologic Eradication at TOC in Participants With cUTI [Test of cure, defined as 7 days after the end of treatment, equivalent to Study Days 14 to 21]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis [End of treatment, Day 7 to 14]

   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.

2. Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

   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.

3. Percentage of Participants With Clinical Cure at Test of Cure in Participants With cUTI [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

   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.

4. Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With cUTI [End of treatment, Day 7 to 14]

   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.

5. Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With cUTI [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

   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.

6. Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall [End of treatment, Day 7 to 14]

   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.

7. Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

   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.

8. Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

   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.

9. Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen [End of treatment, Day 7 to 14]

   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.

10. Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

    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.

11. Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

    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.

12. Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen [End of treatment, Day 7 to 14]

    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.

13. Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

    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.

14. Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

    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.

15. Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis [End of treatment, Day 7 to 14]

    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.

16. Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

    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.

17. Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

    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.

18. Percentage of Participants With Microbiologic Eradication at EOT in Participants With cUTI [End of treatment, Day 7 to 14]

    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.

19. Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With cUTI [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

    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.

20. Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall [End of treatment, Day 7 to 14]

    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.

21. Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

    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.

22. Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

    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.

23. Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen [End of treatment, Day 7 to 14]

    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.

24. Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

    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.

25. Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

    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.

26. Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen [End of treatment, Day 7 to 14]

    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.

27. Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

    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.

28. Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

    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.

29. Percentage of Participants With Microbiologic Eradication at EOT in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia [End of treatment, Day 7 to 14]

    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.

30. Percentage of Participants With Microbiologic Eradication at TOC in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

    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.

31. Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

    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.

32. Percentage of Participants With a Composite Clinical and Microbiological Response at EOT [End of treatment, Day 7 to 14]

    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.

33. Percentage of Participants With a Composite Clinical and Microbiological Response at TOC [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

    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.

34. Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up [Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28]

    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.

35. All-cause Mortality at Day 14 and Day 28 [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.

36. Percentage of Participants Alive and With No Change in Antibiotic Treatment Due to Either Lack of Therapeutic Benefit or Drug-related Toxicity at TOC [Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21]

37. Survival Time [Days 1 to 10, 11 to 20, 21 to 30, 31 to 40, 41-50, and 51 to 60.]

    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

38. Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP) [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)]

    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

39. Change From Baseline in Sequential Organ Failure Assessment (SOFA) [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)]

    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.

40. Number of Participants With Adverse Events [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.]

    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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with clinically documented infection (HAP/VAP/HCAP, cUTI, or BSI/sepsis) caused by a Gram-negative pathogen with evidence of carbapenem resistance

• Patients who have been treated previously with an empiric antibiotic regiment and failed treatment, both clinically and microbiologically, are eligible for the study, if they have an identified carbapenem-resistant Gram-negative pathogen which has either been shown to be nonsusceptible in vitro to each of the antibiotic(s) of the empiric antibiotic regimen or been grown from a culture performed after at least 2 days of the empiric antibiotic regimen

• Patient is male (no contraception required) or female and meets one of the following criteria:

• Surgically sterile by hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy or tubal ligation for the purpose of contraception for at least 6 weeks with appropriate documentation of such surgery

• Postmenopausal (defined as older than 45 years of age with cessation of regular menstrual periods for 6 months and confirmed by a follicle-stimulating hormone level of > 40 mIU/mL, or amenorrhea for at least 12 months)

• Of childbearing potential and using combined (estrogen and progestogen) or progestogen-only hormonal contraception associated with inhibition of ovulation (including oral, intravaginal, injectable, implantable, and transdermal contraceptives), or an intrauterine device (IUD), or intrauterine hormone-releasing system (IUS) for the entire duration of the study

• Of childbearing potential and practice abstinence as a preferred and usual lifestyle, and agrees to continue practicing abstinence from Screening and for the entire duration of the study

• Of childbearing potential, whose sole heterosexual partner has been successfully vasectomized and agrees to not have other heterosexual partners for the entire duration of the study

• Patients meeting specific criteria for each infection site

Exclusion Criteria:

1. Patients who have a history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam (Note: for β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment)

2. Patients who need more than 3 systemic antibiotics as part of best available therapy (BAT) for the treatment of the Gram-negative infection (patients with mixed Gram-positive or anaerobic infections may receive appropriate concomitant narrow spectrum antibiotics [eg, vancomycin, linezolid, metronidazole, clindamycin])

3. Patients with coinfection caused by invasive aspergillosis, mucormycosis or other highly lethal mold

4. Patients who have central nervous system (CNS) infection (eg, meningitis, brain abscess, shunt infection)

5. Patients with infection requiring > 3 weeks of antibiotic treatment (eg, bone and joint infection, endocarditis)

6. Patients with cystic fibrosis or moderate to severe bronchiectasis

7. Patients in refractory septic shock defined as persistent hypotension despite adequate fluid resuscitation or despite vasopressive therapy at the time of Randomization

8. Patients with severe neutropenia, ie, polymorphonuclear neutrophils (PMNs) < 100 cells/μL

9. Female patients who have a positive pregnancy test at Screening or who are lactating

10. Patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 30

11. Patients who have received a potentially effective antibiotic regimen for the carbapenem-resistant Gram-negative infection for a continuous duration of more than 24 hours in cUTI, or 36 hours in HAP/VAP/HCAP or BSI/sepsis during the 72 hours leading to Randomization

12. Patients with any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the study data

13. Patients who have received another investigational drug or device within 30 days prior to study entry

14. Patients who have previously been randomized in this study or received S-649266

15. Patients receiving peritoneal dialysis

16. Patients meeting specific exclusion criteria for each infection site

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shionogi Research Site	Hartford	Connecticut	United States	06102
2	Shionogi Research Site	Newark	Delaware	United States	19718
3	Shionogi Research Site	Chicago	Illinois	United States	60611
4	Shionogi Research Site	New Orleans	Louisiana	United States	70121
5	Shionogi Research Site	Detroit	Michigan	United States	48202
6	Shionogi Research Site	Pittsburgh	Pennsylvania	United States	15213
7	Shionogi Research Site	Salvador	Bahia	Brazil	41810-011
8	Shionogi Research Site	Curitiba	Parana	Brazil	80050
9	Shionogi Research Site	Passo Fundo	RIO Grande DO SUL	Brazil	99010-080
10	Shionogi Research Site	Porto Alegre	RIO Grande DO SUL	Brazil	90035-074
11	Shionogi Research Site	Porto Alegre	RIO Grande DO SUL	Brazil	90035-903
12	Shionogi Research Site	Santa Maria	RIO Grande DO SUL	Brazil	97105-900
13	Shionogi Research Site	São José do Rio Preto	SAO Paulo	Brazil	15090
14	Shionogi Research Site	São Paulo	SAO Paulo	Brazil	04378-000
15	Shionogi Research Site	Rijeka	Primorje-Gorski Kotar	Croatia	51000
16	Shionogi Research Site	Split		Croatia	21000
17	Shionogi Research Site	Zagreb		Croatia	10000
18	Shionogi Research Site	Paris	Ile-de-france	France	75018
19	Shionogi Research Site	La Tronche	Rhone-alpes	France	38043
20	Shionogi Research Site	Heidelberg	Baden-wuerttemberg	Germany	69120
21	Shionogi Research Site	Bonn	Nordrhein-westfalen	Germany	53105
22	Shionogi Research Site	Berlin		Germany	12351
23	Shionogi Research Site	Athens	Attica	Greece	11526
24	Shionogi Research Site	Athens	Attica	Greece	12462
25	Shionogi Research Site	Patra	Peloponnese	Greece	26504
26	Shionogi Research Site	Larisa	Thessaly	Greece	41110
27	Shionogi Research Site	Larisa	Thessaly	Greece	41221
28	Shionogi Research Site	Ciudad de Guatemala		Guatemala
29	Shionogi Research Site	Beer-Sheva	Beersheba	Israel	84101
30	Shionogi Research Site	Be'er Ya'akov	Rehoboth	Israel	70300
31	Shionogi Research Site	Tel Hashomer	Tel Aviv	Israel	52621
32	Shionogi Research Site	Tel-Aviv	Tel Aviv	Israel	64239
33	Shionogi Research Site	Safed	Zefat	Israel	13100
34	Shionogi Research Site	Hadera		Israel	38100
35	Shionogi Research Site	Haifa		Israel	31048
36	Shionogi Research Site	Haifa		Israel	3109601
37	Shionogi Research Site	Holon		Israel	58100
38	Shionogi Research Site	Jerusalem		Israel	91120
39	Shionogi Research Site	Cisanello	Pisa	Italy	56124
40	Shionogi Research Site	Milano		Italy	20122
41	Shionogi Research Site	Milano		Italy	20132
42	Shionogi Research Site	Milano		Italy	20162
43	Shionogi Research Site	Modena		Italy	41124
44	Shionogi Research Site	Udine		Italy	33100
45	Shionogi Research Site	Nagakute	Aichi	Japan	480-1195
46	Shionogi Research Site	Shinagawa-ku	Tokyo	Japan	142-8999
47	Shionogi Research Site	Nagasaki		Japan	852-8501
48	Shionogi Research Site	Wonju-si	Gangwon-Do	Korea, Republic of	26426
49	Shionogi Research Site	Seoul	Gwangjin-gu	Korea, Republic of	5030
50	Shionogi Research Site	Daegu		Korea, Republic of	41931
51	Shionogi Research Site	Daegu		Korea, Republic of	41944
52	Shionogi Research Site	Seoul		Korea, Republic of	06591
53	Shionogi Research Site	Seoul		Korea, Republic of	06973
54	Shionogi Research Site	Seoul		Korea, Republic of	07441
55	Shionogi Research Site	Seoul		Korea, Republic of	135-710
56	Shionogi Research Site	Terrassa	Barcelona	Spain	08035
57	Shionogi Research Site	Córdoba	Cordoba	Spain	14004
58	Shionogi Research Site	Lérida	Lleida	Spain	25198
59	Shionogi Research Site	Barcelona		Spain	08003
60	Shionogi Research Site	Barcelona		Spain	08025
61	Shionogi Research Site	Barcelona		Spain	08036
62	Shionogi Research Site	Ciudad Real		Spain	13005
63	Shionogi Research Site	Gerona		Spain	17007
64	Shionogi Research Site	Madrid		Spain	28046
65	Shionogi Research Site	Malaga		Spain	29010
66	Shionogi Research Site	Sevilla		Spain	41009
67	Shionogi Research Site	Valencia		Spain	46015
68	Shionogi Research Site	Zaragoza		Spain	50009
69	Shionogi Research Site	Taichung	ROC	Taiwan	40705
70	Shionogi Research Site	Taipei City	Taipei	Taiwan	10002
71	Shionogi Research Site	Hualien		Taiwan	97002
72	Shionogi Research Site	Kaohsiung		Taiwan	81362
73	Shionogi Research Site	Taichung		Taiwan	40447
74	Shionogi Research Site	Bangkok		Thailand	10700
75	Shionogi Research Site	Muang Nonthaburi		Thailand	11000
76	Shionogi Research Site	Muang		Thailand	40002
77	Shionogi Research Site	Bornova	Izmir	Turkey	35100
78	Shionogi Research Site	Ankara		Turkey
79	Shionogi Research Site	Istanbul		Turkey	34098
80	Shionogi Research Site	Istanbul		Turkey	34214
81	Shionogi Research Site	Trabzon		Turkey
82	Shionogi Research Site	London	England	United Kingdom	SE1 7EH
83	Shionogi Research Site	London	England	United Kingdom	W 120NN
84	Shionogi Research Site	London	England	United Kingdom	W12 0HS
85	Shionogi Research Site	London	England	United Kingdom

Sponsors and Collaborators

• Shionogi

Investigators

• Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line, Shionogi

Study Documents (Full-Text)

• Statistical Analysis Plan - Jun 27, 2019
• Study Protocol - Nov 16, 2017

More Information

Publications

None provided.

• Responsible Party: Shionogi
• ClinicalTrials.gov Identifier: NCT02714595
• Other Study ID Numbers: 1424R2131; 2015-004703-23
• First Posted: Mar 21, 2016
• Last Update Posted: Jan 12, 2021
• Last Verified: Dec 1, 2020

• Keywords provided by Shionogi: cefiderocol; Bloodstream infections (BSI); Complicated urinary tract infection (cUTI); Ventilator associated pneumonia (VAP); Hospital acquired pneumonia (HAP); Sepsis; multi-drug resistant pathogens; S-649266; Gram-negative pathogens; Healthcare-associated pneumonia (HCAP); carbapenem resistant pathogens
• Additional relevant MeSH terms: Infections; Communicable Diseases; Pneumonia; Sepsis; Urinary Tract Infections; Pneumonia, Ventilator-Associated; Healthcare-Associated Pneumonia

Study Results

Participant Flow

Recruitment Details	This study enrolled hospitalized patients with hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), healthcare-associated pneumonia (HCAP), bloodstream infection (BSI), sepsis, or complicated urinary tract infection (cUTI) caused by carbapenem-resistant Gram-negative pathogens, and was conducted at 95 sites in 16 countries.
Pre-assignment Detail	Participants were randomized in a 2:1 ratio to receive therapy with cefiderocol or best available therapy (BAT), stratified by primary clinical diagnosis (HAP/VAP/HCAP, BSI/sepsis, cUTI), Acute Physiology and Chronic Health Evaluation (APACHE) II score (≤ 15 or ≥ 16-≤ 30), and region (North America, South America region, Europe, Asia-Pacific).

Arm/Group Title	Cefiderocol	Best Available Therapy (BAT)
Arm/Group Description	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Period Title: Overall Study
STARTED	101	51
Received Treatment	101	49
Carbapenem-resistant Microbiological Intent-to-treat	80	38
COMPLETED	69	38
NOT COMPLETED	32	13

Baseline Characteristics

Arm/Group Title	Cefiderocol	Best Available Therapy (BAT)	Total
Arm/Group Description	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Total of all reporting groups
Overall Participants	80	38	118
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.1 (18.7)	62.1 (17.3)	62.8 (18.2)
Age, Customized (Count of Participants)
< 65 years	30 37.5%	21 55.3%	51 43.2%
≥ 65 years	50 62.5%	17 44.7%	67 56.8%
Sex: Female, Male (Count of Participants)
Female	25 31.3%	9 23.7%	34 28.8%
Male	55 68.8%	29 76.3%	84 71.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 12.5%	2 5.3%	12 10.2%
Not Hispanic or Latino	64 80%	35 92.1%	99 83.9%
Unknown or Not Reported	6 7.5%	1 2.6%	7 5.9%
Race/Ethnicity, Customized (Count of Participants)
White	48 60%	27 71.1%	75 63.6%
Asian	24 30%	9 23.7%	33 28%
Other	8 10%	2 5.3%	10 8.5%
Region (Count of Participants)
North America	4 5%	3 7.9%	7 5.9%
South America	7 8.8%	3 7.9%	10 8.5%
Europe	45 56.3%	23 60.5%	68 57.6%
Asia-Pacific	24 30%	9 23.7%	33 28%
Total APACHE II Score (Count of Participants)
≤ 15	41 51.3%	21 55.3%	62 52.5%
≥ 16	39 48.8%	17 44.7%	56 47.5%
Clinical Diagnosis (Count of Participants)
HAP/VAP/HCAP	40 50%	19 50%	59 50%
BSI/Sepsis	23 28.8%	14 36.8%	37 31.4%
cUTI	17 21.3%	5 13.2%	22 18.6%
Sequential Organ Failure Assessment (SOFA) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.6 (4.1)	5.6 (3.9)	5.6 (4.0)
Clinical Pulmonary Infection Score (CPIS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.1 (1.6)	5.0 (1.1)	5.1 (1.4)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat (CR Micro-ITT) Population included all participants who received at least 1 dose of the study treatment, who had a baseline Gram-negative pathogen from an appropriate clinical specimen, and whose baseline Gram-negative pathogen was carbapenem-resistant as confirmed by central laboratory testing.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14
Number (95% Confidence Interval) [percentage of participants]	50.0 62.5%	52.6 138.4%	43.5 36.9%	42.9 NaN

2. Primary Outcome

Title	Percentage of Participants With Microbiologic Eradication at TOC in Participants With cUTI
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	cUTI: Cefiderocol	cUTI: Best Available Therapy
Arm/Group Description	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	17	5
Number (95% Confidence Interval) [percentage of participants]	52.9 66.1%	20.0 52.6%

3. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were counted as non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14
Number (95% Confidence Interval) [percentage of participants]	60.0 75%	63.2 166.3%	69.6 59%	50.0 NaN

4. Secondary Outcome

Title	Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14
Number (95% Confidence Interval) [percentage of participants]	50.0 62.5%	31.6 83.2%	39.1 33.1%	28.6 NaN

5. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at Test of Cure in Participants With cUTI
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders

Arm/Group Title	cUTI: Cefiderocol	cUTI: Best Available Therapy
Arm/Group Description	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	17	5
Number (95% Confidence Interval) [percentage of participants]	70.6 88.3%	60.0 157.9%

6. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With cUTI
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered as non-responders

Arm/Group Title	cUTI: Cefiderocol	cUTI: Best Available Therapy
Arm/Group Description	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	17	5
Number (95% Confidence Interval) [percentage of participants]	76.5 95.6%	60.0 157.9%

7. Secondary Outcome

Title	Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With cUTI
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population); participants with missing data were considered non-responders.

Arm/Group Title	cUTI: Cefiderocol	cUTI: Best Available Therapy
Arm/Group Description	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	17	5
Number (95% Confidence Interval) [percentage of participants]	52.9 66.1%	60.0 157.9%

8. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	63	33	80	38
Number (95% Confidence Interval) [percentage of participants]	63.5 79.4%	57.6 151.6%	66.3 56.2%	57.9 NaN

9. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders

Arm/Group Title	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	63	33	80	38
Number (95% Confidence Interval) [percentage of participants]	47.6 59.5%	48.5 127.6%	52.5 44.5%	50.0 NaN

10. Secondary Outcome

Title	Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	63	33	80	38
Number (95% Confidence Interval) [percentage of participants]	46.0 57.5%	30.3 79.7%	47.5 40.3%	34.2 NaN

11. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	61.5 76.9%	70.0 184.2%	70.0 59.3%	42.9 NaN	0 NaN	63.9 NaN	58.8 NaN	62.2 NaN	58.8 NaN
Pseudomonas aeruginosa	63.6 79.5%	83.3 219.2%	100.0 84.7%	33.3 NaN	50.0 NaN	50.0 NaN	69.2 NaN	66.7 NaN	64.7 NaN	63.6 NaN
Klebsiella pneumoniae	70.0 87.5%	40.0 105.3%	63.6 53.9%	75.0 NaN	90.9 NaN	66.7 NaN	66.7 NaN	55.6 NaN	75.0 NaN	58.3 NaN
Stenotrophomonas maltophilia	20.0 25%	20.0 52.6%	20.0 16.9%
Escherichia coli	100.0 125%	0 0%	100.0 84.7%	100.0 NaN	100.0 NaN	0 NaN	100.0 NaN	0 NaN

12. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	50.0 62.5%	60.0 157.9%	30.0 25.4%	42.9 NaN	0 NaN	44.4 NaN	52.9 NaN	43.2 NaN	52.9 NaN
Pseudomonas aeruginosa	45.5 56.9%	66.7 175.5%	100.0 84.7%	33.3 NaN	50.0 NaN	50.0 NaN	53.8 NaN	55.6 NaN	52.9 NaN	54.5 NaN
Klebsiella pneumoniae	60.0 75%	40.0 105.3%	54.5 46.2%	50.0 NaN	81.8 NaN	66.7 NaN	57.1 NaN	44.4 NaN	65.6 NaN	50.0 NaN
Stenotrophomonas maltophilia	0.0 0%	5.0 13.2%	0.0 0%
Escherichia coli	50.0 62.5%	0.0 0%	50.0 42.4%	100.0 NaN	50.0 NaN	0.0 NaN	60.0 NaN	0.0 NaN

13. Secondary Outcome

Title	Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	50.0 62.5%	60.0 157.9%	30.0 25.4%	28.6 NaN	0.0 NaN	44.4 NaN	35.3 NaN	43.2 NaN	35.3 NaN
Pseudomonas aeruginosa	45.5 56.9%	16.7 43.9%	100.0 84.7%	33.3 NaN	25.0 NaN	50.0 NaN	53.8 NaN	55.6 NaN	47.1 NaN	27.3 NaN
Klebsiella pneumoniae	60.0 75%	40.0 105.3%	45.5 38.6%	25.0 NaN	63.6 NaN	66.7 NaN	52.4 NaN	33.3 NaN	56.3 NaN	41.7 NaN
Stenotrophomonas maltophilia	0.0 0%	0.0 0%	0.0 0%
Escherichia coli	50.0 62.5%	0.0 0%	50.0 42.4%	100.0 NaN	50.0 NaN	0.0 NaN	60.0 NaN	0.0 NaN

14. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	61.5 76.9%	70.0 184.2%	70.0 59.3%	42.9 NaN	0.0 NaN	63.9 NaN	58.8 NaN	62.2 NaN	58.8 NaN
Klebsiella pneumoniae	83.3 104.1%	40.0 105.3%	60.0 50.8%	75.0 NaN	90.9 NaN	66.7 NaN	68.8 NaN	55.6 NaN	77.8 NaN	58.3 NaN
Pseudomonas aeruginosa	50.0 62.5%	80.0 210.5%	100.0 84.7%	33.3 NaN	50.0 NaN	50.0 NaN	62.5 NaN	62.5 NaN	58.3 NaN	60.0 NaN
Stenotrophomonas maltophilia	20.0 25%	20.0 52.6%	20.0 16.9%

15. Secondary Outcome

Title	Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	50.0 62.5%	60.0 157.9%	30.0 25.4%	42.9 NaN	0.0 NaN	44.4 NaN	52.9 NaN	43.2 NaN	52.9 NaN
Klebsiella pneumoniae	66.7 83.4%	40.0 105.3%	50.0 42.4%	50.0 NaN	81.8 NaN	66.7 NaN	56.3 NaN	44.4 NaN	66.7 NaN	50.0 NaN
Pseudomonas aeruginosa	50.0 62.5%	60.0 157.9%	100.0 84.7%	33.3 NaN	50.0 NaN	50.0 NaN	62.5 NaN	50.0 NaN	58.3 NaN	50.0 NaN
Stenotrophomonas maltophilia	0.0 0%	0.0 0%	0.0 0%

16. Secondary Outcome

Title	Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	50.0 62.5%	40.0 105.3%	30.0 25.4%	28.6 NaN	0.0 NaN	44.4 NaN	35.3 NaN	43.2 NaN	35.3 NaN
Klebsiella pneumoniae	66.7 83.4%	40.0 105.3%	40.0 33.9%	25.0 NaN	63.6 NaN	66.7 NaN	50.0 NaN	33.3 NaN	55.6 NaN	41.7 NaN
Pseudomonas aeruginosa	50.0 62.5%	20.0 52.6%	100.0 84.7%	33.3 NaN	25.0 NaN	50.0 NaN	62.5 NaN	25.0 NaN	50.0 NaN	30.0 NaN
Stenotrophomonas maltophilia	0.0 0%	0.0 0%	0.0 0%

17. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14
Number (95% Confidence Interval) [percentage of participants]	30.0 37.5%	26.3 69.2%	60.9 51.6%	28.6 NaN

18. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14
Number (95% Confidence Interval) [percentage of participants]	22.5 28.1%	21.1 55.5%	30.4 25.8%	28.6 NaN

19. Secondary Outcome

Title	Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14
Number (95% Confidence Interval) [percentage of participants]	20.0 25%	15.8 41.6%	26.1 22.1%	21.4 NaN

20. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at EOT in Participants With cUTI
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	cUTI: Cefiderocol	cUTI: Best Available Therapy
Arm/Group Description	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	17	5
Number (95% Confidence Interval) [percentage of participants]	70.6 88.3%	20.0 52.6%

21. Secondary Outcome

Title	Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With cUTI
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	cUTI: Cefiderocol	cUTI: Best Available Therapy
Arm/Group Description	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	17	5
Number (95% Confidence Interval) [percentage of participants]	41.2 51.5%	20.0 52.6%

22. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	63	33	80	38
Number (95% Confidence Interval) [percentage of participants]	41.3 51.6%	27.3 71.8%	47.5 40.3%	26.3 NaN

23. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders

Arm/Group Title	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	63	33	80	38
Number (95% Confidence Interval) [percentage of participants]	25.4 31.8%	24.2 63.7%	31.3 26.5%	23.7 NaN

24. Secondary Outcome

Title	Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP, BSI/sepsis, or cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	63	33	80	38
Number (95% Confidence Interval) [percentage of participants]	22.2 27.8%	18.2 47.9%	26.3 22.3%	18.4 NaN

25. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant Gram-negative pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	34.6 43.3%	30.0 78.9%	60.0 50.8%	28.6 NaN	0.0 NaN	41.7 NaN	29.4 NaN	40.5 NaN	29.4 NaN
Pseudomonas aeruginosa	36.4 45.5%	33.3 87.6%	0.0 0%	33.3 NaN	50.0 NaN	50.0 NaN	30.8 NaN	33.3 NaN	35.3 NaN	36.4 NaN
Klebsiella pneumoniae	50.0 62.5%	20.0 52.6%	72.7 61.6%	25.0 NaN	81.8 NaN	0.0 NaN	61.9 NaN	22.2 NaN	68.8 NaN	16.7 NaN
Stenotrophomonas maltophilia	20.0 25%	20.0 52.6%	20.0 16.9%
Escherichia coli	100.0 125%	0.0 0%	100.0 84.7%	100.0 NaN	100.0 NaN	0.0 NaN	100.0 NaN	0.0 NaN

26. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant Gram-negative pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	30.8 38.5%	30.0 78.9%	20.0 16.9%	28.6 NaN	0.0 NaN	27.8 NaN	29.4 NaN	27.0 NaN	29.4 NaN
Pseudomonas aeruginosa	9.1 11.4%	16.7 43.9%	0.0 0%	0.0 NaN	25.0 NaN	50.0 NaN	7.7 NaN	11.1 NaN	11.8 NaN	18.2 NaN
Klebsiella pneumoniae	50.0 62.5%	20.0 52.6%	54.5 46.2%	50.0 NaN	72.7 NaN	0.0 NaN	38.1 NaN	33.3 NaN	50.0 NaN	25.0 NaN
Stenotrophomonas maltophilia	0.0 0%	0.0 0%	0.0 0%
Escherichia coli	50.0 62.5%	0.0 0%	100.0 84.7%	0.0 NaN	50.0 NaN	0.0 NaN	40.0 NaN	0.0 NaN

27. Secondary Outcome

Title	Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant Gram-negative pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	26.9 33.6%	20.0 52.6%	20.0 16.9%	14.3 NaN	0.0 NaN	25.0 NaN	17.6 NaN	24.3 NaN	17.6 NaN
Pseudomonas aeruginosa	9.1 11.4%	16.7 43.9%	0.0 0%	0.0 NaN	0.0 NaN	50.0 NaN	7.7 NaN	11.1 NaN	5.9 NaN	18.2 NaN
Klebsiella pneumoniae	20.0 25%	20.0 52.6%	45.5 38.6%	50.0 NaN	63.6 NaN	0.0 NaN	33.3 NaN	33.3 NaN	43.8 NaN	25.0 NaN
Stenotrophomonas maltophilia	0.0 0%	0.0 0%	0.0 0%
Escherichia coli	50.0 62.5%	0.0 0%	50.0 42.4%	0.0 NaN	50.0 NaN	0.0 NaN	40.0 NaN	0.0 NaN

28. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	34.6 43.3%	30.0 78.9%	60.0 50.8%	28.6 NaN	0.0 NaN	41.7 NaN	29.4 NaN	40.5 NaN	29.4 NaN
Klebsiella pneumoniae	33.3 41.6%	20.0 52.6%	70.0 59.3%	75.0 NaN	81.8 NaN	0.0 NaN	56.3 NaN	22.2 NaN	66.7 NaN	16.7 NaN
Pseudomonas aeruginosa	33.3 41.6%	40.0 105.3%	0.0 0%	33.3 NaN	50.0 NaN	50.0 NaN	25.0 NaN	37.5 NaN	33.3 NaN	40.0 NaN
Stenotrophomonas maltophilia	20.0 25%	20. 52.6%	20.0 16.9%

29. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	30.8 38.5%	30.0 78.9%	20.0 16.9%	28.6 NaN	0.0 NaN	27.8 NaN	29.4 NaN	27.0 NaN	29.4 NaN
Klebsiella pneumoniae	0.0 0%	20.0 52.6%	50.0 42.4%	50.0 NaN	72.7 NaN	0.0 NaN	31.3 NaN	33.3 NaN	48.1 NaN	25.0 NaN
Pseudomonas aeruginosa	0.0 0%	20.0 52.6%	0.0 0%	0.0 NaN	25.0 NaN	50.0 NaN	0.0 NaN	12.5 NaN	8.3 NaN	20.0 NaN
Stenotrophomonas maltophilia	0.0 0%	0.0 0%	0.0 0%

30. Secondary Outcome

Title	Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Acinetobacter baumannii	26.9 33.6%	20.0 52.6%	20.0 16.9%	14.3 NaN	0.0 NaN	25.0 NaN	17.6 NaN	24.3 NaN	17.6 NaN
Klebsiella pneumoniae	0.0 0%	20.0 52.6%	40.0 33.9%	50.0 NaN	63.6 NaN	0.0 NaN	25.0 NaN	33.3 NaN	40.7 NaN	25.0 NaN
Pseudomonas aeruginosa	0.0 0%	20.0 52.6%	0.0 0%	0.0 NaN	0.0 NaN	50.0 NaN	0.0 NaN	12.5 NaN	0.0 NaN	20.0 NaN
Stenotrophomonas maltophilia	0.0 0%	0.0 0%	0.0 0%

31. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at EOT in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with documented carbapenem-resistant Gram-negative bacteremia at Baseline (all infection sites combined); participants with missing data were considered non-responders.

Arm/Group Title	Cefiderocol	Best Available Therapy (BAT)
Arm/Group Description	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	22	13
Number (95% Confidence Interval) [percentage of participants]	54.5 68.1%	30.8 81.1%

32. Secondary Outcome

Title	Percentage of Participants With Microbiologic Eradication at TOC in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with documented carbapenem-resistant Gram-negative bacteremia at Baseline (all infection sites combined); participants with missing data were considered non-responders.

Arm/Group Title	Cefiderocol	Best Available Therapy (BAT)
Arm/Group Description	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	22	13
Number (95% Confidence Interval) [percentge of participants]	31.8 39.8%	30.8 81.1%

33. Secondary Outcome

Title	Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population with documented carbapenem-resistant Gram-negative bacteremia at Baseline (all infection sites combined); participants with missing data were considered non-responders.

Arm/Group Title	Cefiderocol	Best Available Therapy (BAT)
Arm/Group Description	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	22	13
Number (95% Confidence Interval) [percentage of participants]	27.3 34.1%	23.1 60.8%

34. Secondary Outcome

Title	Percentage of Participants With a Composite Clinical and Microbiological Response at EOT
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Number (95% Confidence Interval) [percentage of participants]	30.0 37.5%	26.3 69.2%	56.5 47.9%	21.4 NaN	70.6 NaN	20.0 NaN	39.7 NaN	24.2 NaN	46.3 NaN	23.7 NaN

35. Secondary Outcome

Title	Percentage of Participants With a Composite Clinical and Microbiological Response at TOC
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Number (95% Confidence Interval) [percentage of participants]	22.5 28.1%	21.1 55.5%	30.4 25.8%	21.4 NaN	47.1 NaN	20.0 NaN	25.4 NaN	21.2 NaN	30.0 NaN	21.1 NaN

36. Secondary Outcome

Title	Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up
Description	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	63	33	80	38
Number (95% Confidence Interval) [percentage of participants]	20.0 25%	15.8 41.6%	26.1 22.1%	14.3 NaN	41.2 NaN	20.0 NaN	22.2 NaN	15.2 NaN	26.3 NaN	15.8 NaN

37. Secondary Outcome

Title	All-cause Mortality at Day 14 and Day 28
Description	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

Outcome Measure Data

Analysis Population Description

The safety population includes randomized participants who received at least 1 dose of study drug.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol	HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP or BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	45	22	30	17	26	10	75	39	101	49
Day 14	24.4 30.5%	13.6 35.8%	16.7 14.2%	5.9 NaN	11.5 NaN	20.0 NaN	21.3 NaN	10.3 NaN	18.8 NaN	12.2 NaN
Day 28	31.1 38.9%	18.2 47.9%	23.3 19.7%	17.6 NaN	15.4 NaN	20.0 NaN	28.0 NaN	17.9 NaN	24.8 NaN	18.4 NaN

38. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population

Arm/Group Title	Cefiderocol	Best Available Therapy (BAT)
Arm/Group Description	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	80	38
Number (95% Confidence Interval) [percentage of participants]	62.5 78.1%	60.5 159.2%

39. Secondary Outcome

Title	Survival Time
Description	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.

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant Microbiological Intent-to-treat Population

Arm/Group Title	Cefiderocol	Best Available Therapy (BAT)
Arm/Group Description	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	80	38
Days 1 to 10	12 15%	3 7.9%
Days 11 to 20	9 11.3%	3 7.9%
Days 21 to 30	1 1.3%	2 5.3%
Days 31 to 40	4 5%	0 0%
Days 41 to 50	1 1.3%	0 0%
Days 51 to 60	0 0%	0 0%

40. Secondary Outcome

Title	Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP)
Description	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)

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant microbiological intention-to-treat population; Participants with pneumonia and CPIS measurement at Baseline and at each post-baseline time point.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	39	18
End of treatment	-2.5 (2.2)	-1.9 (1.7)
Test of cure	-3.1 (2.1)	-2.7 (2.2)
Follow-up	-3.4 (1.8)	-2.7 (1.9)

41. Secondary Outcome

Title	Change From Baseline in Sequential Organ Failure Assessment (SOFA)
Description	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)

Outcome Measure Data

Analysis Population Description

Carbapenem-resistant microbiological intention-to-treat population with SOFA measurement at Baseline and at each post-baseline time point.

Arm/Group Title	HAP/VAP/HCAP: Cefiderocol	HAP/VAP/HCAP: Best Available Therapy	BSI/Sepsis: Cefiderocol	BSI/Sepsis: Best Available Therapy	cUTI: Cefiderocol	cUTI: Best Available Therapy	Overall: Cefiderocol	Overall: Best Available Therapy
Arm/Group Description	Participants with HAP/VAP/HCAP received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with HAP/VAP/HCAP received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with BSI/sepsis received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with BSI/sepsis received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants with cUTI received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants with cUTI received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, which may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	40	19	23	14	17	5	80	38
End of treatment	-0.7 (3.6)	-1.6 (2.6)	-2.1 (3.7)	-0.2 (2.8)	-0.6 (1.3)	-1.3 (2.3)	-1.1 (3.3)	-1.0 (2.7)
Test of cure	-1.3 (5.0)	-1.7 (2.9)	-2.1 (2.5)	0.2 (4.1)	-0.6 (2.0)	-1.3 (2.3)	-1.3 (3.8)	-0.9 (3.4)
Follow-up	-2.1 (4.4)	-2.0 (2.9)	-3.1 (3.1)	-0.2 (4.4)	-0.1 (2.5)	-2.0 (3.5)	-1.9 (3.8)	-1.4 (3.5)

42. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	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.

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Cefiderocol	Best Available Therapy (BAT)
Arm/Group Description	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.	Participants received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
Measure Participants	101	49
Any adverse event (AE)	92 115%	47 123.7%
Mild adverse events	23 28.8%	9 23.7%
Moderate adverse events	26 32.5%	16 42.1%
Severe adverse events	43 53.8%	22 57.9%
Drug-related adverse events	15 18.8%	11 28.9%
Discontinuations due to adverse events	10 12.5%	3 7.9%
Discontinuations due to drug-related AEs	3 3.8%	2 5.3%
Serious adverse events (SAE)	50 62.5%	23 60.5%
Drug-related serious adverse events	1 1.3%	5 13.2%
Death due to serious adverse events	34 42.5%	9 23.7%

Adverse Events

Time Frame	From first dose of study drug up to 28 days after last dose; For patients with HAP/VAP/HCAP or BSI/sepsis median treatment duration was 11.0 (2-22) days (cefiderocol) and 13.0 (2-22) days (BAT); In patients with cUTI median treatment duration was 10.5 (2-29) days (cefiderocol) and 6.5 (2-14) days (BAT).
Arm/Group Title	Cefiderocol		Best Available Therapy (BAT)
Arm/Group Description	Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days.		Participants received best available therapy, as chosen by the investigator, and may have included up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days.
All Cause Mortality
	Cefiderocol		Best Available Therapy (BAT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/101 (33.7%)		9/49 (18.4%)
Serious Adverse Events
	Cefiderocol		Best Available Therapy (BAT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/101 (49.5%)		23/49 (46.9%)
Blood and lymphatic system disorders
Anaemia	0/101 (0%)		1/49 (2%)
Febrile neutropenia	1/101 (1%)		0/49 (0%)
Cardiac disorders
Bradycardia	1/101 (1%)		1/49 (2%)
Cardiac arrest	4/101 (4%)		2/49 (4.1%)
Cardiac failure congestive	1/101 (1%)		0/49 (0%)
Myocardial infarction	1/101 (1%)		0/49 (0%)
Pulseless electrical activity	0/101 (0%)		1/49 (2%)
Gastrointestinal disorders
Abdominal pain	1/101 (1%)		0/49 (0%)
Abdominal pain upper	1/101 (1%)		0/49 (0%)
Gastrointestinal haemorrhage	1/101 (1%)		0/49 (0%)
Intestinal ischaemia	1/101 (1%)		0/49 (0%)
Lower gastrointestinal haemorrhage	1/101 (1%)		0/49 (0%)
Pancreatitis	1/101 (1%)		0/49 (0%)
Small intestinal obstruction	1/101 (1%)		0/49 (0%)
General disorders
Chills	1/101 (1%)		0/49 (0%)
General physical health deterioration	0/101 (0%)		1/49 (2%)
Multi-organ failure	2/101 (2%)		2/49 (4.1%)
Pyrexia	3/101 (3%)		0/49 (0%)
Sudden death	1/101 (1%)		0/49 (0%)
Hepatobiliary disorders
Chronic hepatic failure	1/101 (1%)		0/49 (0%)
Hepatic failure	1/101 (1%)		0/49 (0%)
Hepatitis	1/101 (1%)		0/49 (0%)
Immune system disorders
Anaphylactic reaction	0/101 (0%)		1/49 (2%)
Infections and infestations
Bacteraemia	3/101 (3%)		0/49 (0%)
Bacterial infection	1/101 (1%)		0/49 (0%)
Device related infection	0/101 (0%)		1/49 (2%)
Empyema	1/101 (1%)		1/49 (2%)
Endocarditis	0/101 (0%)		1/49 (2%)
Enterococcal bacteraemia	1/101 (1%)		0/49 (0%)
Enterococcal infection	2/101 (2%)		0/49 (0%)
Meningitis	0/101 (0%)		1/49 (2%)
Necrotising fasciitis	0/101 (0%)		1/49 (2%)
Osteomyelitis	1/101 (1%)		0/49 (0%)
Osteomyelitis acute	0/101 (0%)		1/49 (2%)
Pneumonia	5/101 (5%)		1/49 (2%)
Pneumonia bacterial	1/101 (1%)		0/49 (0%)
Renal abscess	1/101 (1%)		0/49 (0%)
Sepsis	3/101 (3%)		0/49 (0%)
Septic shock	12/101 (11.9%)		6/49 (12.2%)
Systemic candida	1/101 (1%)		0/49 (0%)
Urinary tract infection	1/101 (1%)		0/49 (0%)
Urosepsis	1/101 (1%)		0/49 (0%)
Investigations
Liver function test abnormal	4/101 (4%)		3/49 (6.1%)
Transaminases increased	1/101 (1%)		0/49 (0%)
Metabolism and nutrition disorders
Hyponatraemia	1/101 (1%)		0/49 (0%)
Metabolic acidosis	2/101 (2%)		1/49 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/101 (1%)		0/49 (0%)
Nervous system disorders
Dizziness	1/101 (1%)		0/49 (0%)
Hypoaesthesia	1/101 (1%)		0/49 (0%)
Neurological decompensation	1/101 (1%)		0/49 (0%)
Paraesthesia	1/101 (1%)		0/49 (0%)
Quadriplegia	0/101 (0%)		1/49 (2%)
Status epilepticus	0/101 (0%)		1/49 (2%)
Renal and urinary disorders
Acute kidney injury	3/101 (3%)		2/49 (4.1%)
Anuria	1/101 (1%)		0/49 (0%)
Nephrolithiasis	1/101 (1%)		0/49 (0%)
Oliguria	2/101 (2%)		0/49 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/101 (1%)		1/49 (2%)
Chronic obstructive pulmonary disease	1/101 (1%)		0/49 (0%)
Obstructive airways disorder	1/101 (1%)		0/49 (0%)
Pneumonia aspiration	2/101 (2%)		0/49 (0%)
Respiratory arrest	0/101 (0%)		1/49 (2%)
Respiratory failure	2/101 (2%)		0/49 (0%)
Vascular disorders
Hypotension	2/101 (2%)		1/49 (2%)
Shock	1/101 (1%)		1/49 (2%)
Other (Not Including Serious) Adverse Events
	Cefiderocol		Best Available Therapy (BAT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/101 (87.1%)		43/49 (87.8%)
Blood and lymphatic system disorders
Anaemia	8/101 (7.9%)		1/49 (2%)
Anaemia of chronic disease	1/101 (1%)		1/49 (2%)
Febrile neutropenia	0/101 (0%)		1/49 (2%)
Leukopenia	2/101 (2%)		1/49 (2%)
Splenic infarction	0/101 (0%)		1/49 (2%)
Thrombocytopenia	6/101 (5.9%)		4/49 (8.2%)
Thrombocytosis	3/101 (3%)		1/49 (2%)
Cardiac disorders
Atrial fibrillation	2/101 (2%)		1/49 (2%)
Atrial flutter	0/101 (0%)		1/49 (2%)
Bradycardia	3/101 (3%)		2/49 (4.1%)
Cyanosis	0/101 (0%)		1/49 (2%)
Myocardial ischaemia	0/101 (0%)		1/49 (2%)
Sinus tachycardia	0/101 (0%)		1/49 (2%)
Tachycardia	1/101 (1%)		2/49 (4.1%)
Endocrine disorders
Hypothyroidism	0/101 (0%)		1/49 (2%)
Eye disorders
Ocular hyperaemia	0/101 (0%)		1/49 (2%)
Pupils unequal	0/101 (0%)		1/49 (2%)
Gastrointestinal disorders
Abdominal distension	1/101 (1%)		1/49 (2%)
Abdominal pain	5/101 (5%)		4/49 (8.2%)
Abdominal pain lower	0/101 (0%)		1/49 (2%)
Abdominal pain upper	3/101 (3%)		0/49 (0%)
Constipation	8/101 (7.9%)		3/49 (6.1%)
Diarrhoea	19/101 (18.8%)		6/49 (12.2%)
Dysphagia	0/101 (0%)		1/49 (2%)
Gastrointestinal haemorrhage	0/101 (0%)		1/49 (2%)
Haematemesis	1/101 (1%)		1/49 (2%)
Impaired gastric emptying	1/101 (1%)		1/49 (2%)
Intra-abdominal haemorrhage	0/101 (0%)		1/49 (2%)
Melaena	1/101 (1%)		2/49 (4.1%)
Nausea	7/101 (6.9%)		2/49 (4.1%)
Rectal haemorrhage	0/101 (0%)		1/49 (2%)
Upper gastrointestinal haemorrhage	3/101 (3%)		0/49 (0%)
Vomiting	13/101 (12.9%)		7/49 (14.3%)
General disorders
Asthenia	2/101 (2%)		1/49 (2%)
Catheter site inflammation	0/101 (0%)		1/49 (2%)
Chest pain	6/101 (5.9%)		0/49 (0%)
Fatigue	1/101 (1%)		2/49 (4.1%)
Hypothermia	2/101 (2%)		1/49 (2%)
Localised oedema	1/101 (1%)		1/49 (2%)
Malaise	1/101 (1%)		1/49 (2%)
Oedema	4/101 (4%)		0/49 (0%)
Oedema peripheral	5/101 (5%)		2/49 (4.1%)
Pain	2/101 (2%)		1/49 (2%)
Pyrexia	12/101 (11.9%)		6/49 (12.2%)
Hepatobiliary disorders
Biliary dilatation	0/101 (0%)		1/49 (2%)
Cholangitis	1/101 (1%)		1/49 (2%)
Gallbladder necrosis	0/101 (0%)		1/49 (2%)
Infections and infestations
Abdominal abscess	0/101 (0%)		1/49 (2%)
Acinetobacter infection	1/101 (1%)		1/49 (2%)
Bacteraemia	1/101 (1%)		1/49 (2%)
Bacterial disease carrier	1/101 (1%)		1/49 (2%)
Bacterial infection	3/101 (3%)		0/49 (0%)
Candida infection	4/101 (4%)		1/49 (2%)
Candiduria	2/101 (2%)		1/49 (2%)
Catheter site infection	0/101 (0%)		1/49 (2%)
Cellulitis	2/101 (2%)		1/49 (2%)
Conjunctivitis	0/101 (0%)		1/49 (2%)
Corynebacterium infection	0/101 (0%)		1/49 (2%)
Cytomegalovirus viraemia	0/101 (0%)		1/49 (2%)
Enterobacter infection	0/101 (0%)		1/49 (2%)
Enterococcal infection	2/101 (2%)		1/49 (2%)
Influenza	0/101 (0%)		1/49 (2%)
Klebsiella infection	0/101 (0%)		1/49 (2%)
Oral herpes	2/101 (2%)		1/49 (2%)
Oropharyngeal candidiasis	0/101 (0%)		1/49 (2%)
Osteomyelitis	0/101 (0%)		1/49 (2%)
Otitis externa	0/101 (0%)		1/49 (2%)
Pneumonia bacterial	2/101 (2%)		1/49 (2%)
Pseudomembranous colitis	1/101 (1%)		1/49 (2%)
Pseudomonas infection	1/101 (1%)		1/49 (2%)
Sepsis	1/101 (1%)		3/49 (6.1%)
Septic shock	1/101 (1%)		1/49 (2%)
Staphylococcal infection	0/101 (0%)		2/49 (4.1%)
Staphylococcal sepsis	0/101 (0%)		1/49 (2%)
Streptococcal bacteraemia	0/101 (0%)		1/49 (2%)
Systemic candida	3/101 (3%)		1/49 (2%)
Tracheobronchitis	1/101 (1%)		1/49 (2%)
Urinary tract infection	1/101 (1%)		2/49 (4.1%)
Urinary tract infection enterococcal	3/101 (3%)		0/49 (0%)
Wound infection pseudomonas	0/101 (0%)		1/49 (2%)
Injury, poisoning and procedural complications
Procedural haemorrhage	0/101 (0%)		1/49 (2%)
Procedural pain	4/101 (4%)		0/49 (0%)
Transfusion reaction	0/101 (0%)		1/49 (2%)
Wound	0/101 (0%)		1/49 (2%)
Investigations
Activated partial thromboplastin time prolonged	1/101 (1%)		1/49 (2%)
Alanine aminotransferase increased	7/101 (6.9%)		0/49 (0%)
Aspartate aminotransferase increased	8/101 (7.9%)		1/49 (2%)
Blood bilirubin increased	2/101 (2%)		1/49 (2%)
Blood creatine increased	0/101 (0%)		2/49 (4.1%)
Blood creatinine increased	4/101 (4%)		2/49 (4.1%)
Blood lactate dehydrogenase increased	1/101 (1%)		1/49 (2%)
Blood lactic acid increased	1/101 (1%)		1/49 (2%)
Blood magnesium decreased	3/101 (3%)		0/49 (0%)
Blood phosphorus decreased	0/101 (0%)		2/49 (4.1%)
Blood urea increased	1/101 (1%)		1/49 (2%)
Gastrointestinal stoma output increased	0/101 (0%)		1/49 (2%)
Hepatic enzyme increased	0/101 (0%)		1/49 (2%)
International normalised ratio increased	2/101 (2%)		1/49 (2%)
Lipase increased	0/101 (0%)		1/49 (2%)
Liver function test abnormal	4/101 (4%)		1/49 (2%)
Platelet count decreased	0/101 (0%)		2/49 (4.1%)
White blood cell count abnormal	0/101 (0%)		1/49 (2%)
White blood cell count increased	0/101 (0%)		2/49 (4.1%)
Metabolism and nutrition disorders
Acidosis	0/101 (0%)		2/49 (4.1%)
Fluid overload	1/101 (1%)		1/49 (2%)
Hyperglycaemia	3/101 (3%)		1/49 (2%)
Hyperkalaemia	5/101 (5%)		6/49 (12.2%)
Hyperlipidaemia	0/101 (0%)		1/49 (2%)
Hypernatraemia	2/101 (2%)		1/49 (2%)
Hyperphosphataemia	1/101 (1%)		2/49 (4.1%)
Hypocalcaemia	1/101 (1%)		2/49 (4.1%)
Hypoglycaemia	4/101 (4%)		2/49 (4.1%)
Hypokalaemia	9/101 (8.9%)		7/49 (14.3%)
Hypomagnesaemia	6/101 (5.9%)		4/49 (8.2%)
Hyponatraemia	3/101 (3%)		0/49 (0%)
Hypophosphataemia	0/101 (0%)		2/49 (4.1%)
Metabolic acidosis	1/101 (1%)		2/49 (4.1%)
Metabolic alkalosis	1/101 (1%)		1/49 (2%)
Vitamin D deficiency	1/101 (1%)		1/49 (2%)
Musculoskeletal and connective tissue disorders
Back pain	1/101 (1%)		1/49 (2%)
Gouty arthritis	0/101 (0%)		1/49 (2%)
Joint effusion	0/101 (0%)		1/49 (2%)
Musculoskeletal chest pain	0/101 (0%)		1/49 (2%)
Pain in extremity	2/101 (2%)		2/49 (4.1%)
Nervous system disorders
Cerebral small vessel ischaemic disease	0/101 (0%)		1/49 (2%)
Dizziness	0/101 (0%)		2/49 (4.1%)
Dizziness postural	0/101 (0%)		1/49 (2%)
Headache	3/101 (3%)		0/49 (0%)
Polyneuropathy	0/101 (0%)		1/49 (2%)
Psychiatric disorders
Agitation	5/101 (5%)		2/49 (4.1%)
Anxiety	2/101 (2%)		2/49 (4.1%)
Confusional state	2/101 (2%)		1/49 (2%)
Delirium	4/101 (4%)		0/49 (0%)
Depression	0/101 (0%)		3/49 (6.1%)
Insomnia	2/101 (2%)		3/49 (6.1%)
Restlessness	3/101 (3%)		1/49 (2%)
Renal and urinary disorders
Acute kidney injury	4/101 (4%)		4/49 (8.2%)
Bladder disorder	0/101 (0%)		1/49 (2%)
Oliguria	2/101 (2%)		2/49 (4.1%)
Renal disorder	0/101 (0%)		1/49 (2%)
Renal impairment	0/101 (0%)		1/49 (2%)
Renal tubular acidosis	0/101 (0%)		1/49 (2%)
Urinary retention	0/101 (0%)		1/49 (2%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/101 (0%)		1/49 (2%)
Genital erythema	0/101 (0%)		1/49 (2%)
Oedema genital	0/101 (0%)		1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Alveolitis allergic	0/101 (0%)		1/49 (2%)
Atelectasis	0/101 (0%)		1/49 (2%)
Cough	3/101 (3%)		1/49 (2%)
Dyspnoea	7/101 (6.9%)		2/49 (4.1%)
Haemoptysis	4/101 (4%)		0/49 (0%)
Hiccups	2/101 (2%)		1/49 (2%)
Lung consolidation	0/101 (0%)		1/49 (2%)
Lung infiltration	0/101 (0%)		1/49 (2%)
Pleural effusion	8/101 (7.9%)		1/49 (2%)
Pneumothorax	3/101 (3%)		0/49 (0%)
Pulmonary oedema	1/101 (1%)		2/49 (4.1%)
Respiratory acidosis	1/101 (1%)		1/49 (2%)
Respiratory failure	1/101 (1%)		1/49 (2%)
Tachypnoea	0/101 (0%)		2/49 (4.1%)
Skin and subcutaneous tissue disorders
Blister	0/101 (0%)		1/49 (2%)
Decubitus ulcer	10/101 (9.9%)		4/49 (8.2%)
Dermatitis contact	0/101 (0%)		1/49 (2%)
Erythema	1/101 (1%)		2/49 (4.1%)
Night sweats	0/101 (0%)		1/49 (2%)
Pruritus	1/101 (1%)		1/49 (2%)
Rash	3/101 (3%)		4/49 (8.2%)
Skin fissures	0/101 (0%)		1/49 (2%)
Vascular disorders
Haemorrhage	0/101 (0%)		1/49 (2%)
Hypertension	3/101 (3%)		2/49 (4.1%)
Hypotension	6/101 (5.9%)		2/49 (4.1%)
Shock	0/101 (0%)		1/49 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.