Healthcare-associated Pneumonia (HCAP), Bloodstream Infections (BSI), Hospital Acquired Pneumonia (HAP), Complicated Urinary Tract Infection (cUTI), Sepsis, Ventilator Associated Pneumonia (VAP)
Conditions
Keywords
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
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.
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.
Interventions
DRUGCefiderocol
2 g intravenously over 3 hours every 8 hours for a period of 7 to 14 days, or 2 g every 6 hours for participants with creatinine clearance \>120 mL/min.
Standard of care with either a polymyxin-based or non-polymyxin-based regimen as determined by the investigator and consisting of one to three marketed antibacterial agent(s).
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 | — |
| 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. |
| 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 |
| 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. |
| 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 |
| 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 |
| 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. |
Countries
Brazil, Croatia, France, Germany, Greece, Guatemala, Israel, Italy, Japan, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
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 details
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).
Participants by arm
| Arm | Count |
|---|---|
| Cefiderocol Participants received 2 g cefiderocol administered intravenously over 3 hours, every 8 hours for 7-14 days. | 80 |
| Best Available Therapy (BAT) 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. | 38 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 30 | 9 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other-Miscellaneous | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Cefiderocol | Best Available Therapy (BAT) | Total |
|---|---|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 18.7 | 62.1 years STANDARD_DEVIATION 17.3 | 62.8 years STANDARD_DEVIATION 18.2 |
| Age, Customized < 65 years | 30 Participants | 21 Participants | 51 Participants |
| Age, Customized ≥ 65 years | 50 Participants | 17 Participants | 67 Participants |
| Clinical Diagnosis BSI/Sepsis | 23 Participants | 14 Participants | 37 Participants |
| Clinical Diagnosis cUTI | 17 Participants | 5 Participants | 22 Participants |
| Clinical Diagnosis HAP/VAP/HCAP | 40 Participants | 19 Participants | 59 Participants |
| Clinical Pulmonary Infection Score (CPIS) | 5.1 units on a scale STANDARD_DEVIATION 1.6 | 5.0 units on a scale STANDARD_DEVIATION 1.1 | 5.1 units on a scale STANDARD_DEVIATION 1.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 2 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants | 35 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian | 24 Participants | 9 Participants | 33 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 2 Participants | 10 Participants |
| Race/Ethnicity, Customized White | 48 Participants | 27 Participants | 75 Participants |
| Region Asia-Pacific | 24 Participants | 9 Participants | 33 Participants |
| Region Europe | 45 Participants | 23 Participants | 68 Participants |
| Region North America | 4 Participants | 3 Participants | 7 Participants |
| Region South America | 7 Participants | 3 Participants | 10 Participants |
| Sequential Organ Failure Assessment (SOFA) Score | 5.6 units on a scale STANDARD_DEVIATION 4.1 | 5.6 units on a scale STANDARD_DEVIATION 3.9 | 5.6 units on a scale STANDARD_DEVIATION 4 |
| Sex: Female, Male Female | 25 Participants | 9 Participants | 34 Participants |
| Sex: Female, Male Male | 55 Participants | 29 Participants | 84 Participants |
| Total APACHE II Score ≤ 15 | 41 Participants | 21 Participants | 62 Participants |
| Total APACHE II Score ≥ 16 | 39 Participants | 17 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 34 / 101 | 9 / 49 |
| other Total, other adverse events | 88 / 101 | 43 / 49 |
| serious Total, serious adverse events | 50 / 101 | 23 / 49 |
Outcome results
Primary
Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. Participants with missing data were considered as non-responders.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 50.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 52.6 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 43.5 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 42.9 percentage of participants |
Primary
Percentage of Participants With Microbiologic Eradication at TOC in Participants With cUTI
Microbiological outcome per Baseline pathogen was determined by the sponsor as defined for each infection site. For cUTI eradication was defined as a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ colony-forming units (CFU)/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after the end of treatment, equivalent to Study Days 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC in Participants With cUTI | 52.9 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC in Participants With cUTI | 20.0 percentage of participants |
Secondary
All-cause Mortality at Day 14 and Day 28
The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants who experienced mortality regardless of the cause at or before Day 14 and Day 28, respectively.
Time frame: Day 14 and Day 28
Population: The safety population includes randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 14 | 24.4 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 28 | 31.1 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 14 | 13.6 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 28 | 18.2 percentage of participants |
| BSI/Sepsis: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 14 | 16.7 percentage of participants |
| BSI/Sepsis: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 28 | 23.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 14 | 5.9 percentage of participants |
| BSI/Sepsis: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 28 | 17.6 percentage of participants |
| cUTI: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 28 | 15.4 percentage of participants |
| cUTI: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 14 | 11.5 percentage of participants |
| cUTI: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 28 | 20.0 percentage of participants |
| cUTI: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 14 | 20.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 28 | 28.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 14 | 21.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 14 | 10.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 28 | 17.9 percentage of participants |
| Overall: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 14 | 18.8 percentage of participants |
| Overall: Cefiderocol | All-cause Mortality at Day 14 and Day 28 | Day 28 | 24.8 percentage of participants |
| Overall: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 14 | 12.2 percentage of participants |
| Overall: Best Available Therapy | All-cause Mortality at Day 14 and Day 28 | Day 28 | 18.4 percentage of participants |
Secondary
Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP)
Clinical pulmonary infection score (CPIS) is a surrogate for diagnosis and treatment response. Points (0, 1, or 2) are assigned for observed findings for 5 variables including body temperature, white blood cell count, tracheal secretions, ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), and chest radiograph infiltrates. The total score ranges from 0 to 10, where higher scores may indicate a higher likelihood of mortality; a negative change from Baseline indicates improvement
Time frame: Baseline, end of treatment (Day 7-14), test of cure (7 days after end of treatment, equivalent to Study Day 14 to 21) and follow-up (14 days after end of treatment, equivalent to Study Day 21 to 28)
Population: Carbapenem-resistant microbiological intention-to-treat population; Participants with pneumonia and CPIS measurement at Baseline and at each post-baseline time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP) | End of treatment | -2.5 scores on a scale | Standard Deviation 2.2 |
| HAP/VAP/HCAP: Cefiderocol | Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP) | Test of cure | -3.1 scores on a scale | Standard Deviation 2.1 |
| HAP/VAP/HCAP: Cefiderocol | Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP) | Follow-up | -3.4 scores on a scale | Standard Deviation 1.8 |
| HAP/VAP/HCAP: Best Available Therapy | Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP) | End of treatment | -1.9 scores on a scale | Standard Deviation 1.7 |
| HAP/VAP/HCAP: Best Available Therapy | Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP) | Test of cure | -2.7 scores on a scale | Standard Deviation 2.2 |
| HAP/VAP/HCAP: Best Available Therapy | Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP) | Follow-up | -2.7 scores on a scale | Standard Deviation 1.9 |
Secondary
Change From Baseline in Sequential Organ Failure Assessment (SOFA)
The SOFA score is a scoring system to determine the extent of a patient's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each score is from 0 to 4, and the total score ranges from 0 to 24, where higher scores indicate a higher likelihood of mortality. A negative change from Baseline score indicates improvement.
Time frame: Baseline, end of treatment (Day 7 to 14), test of cure (7 days after end of treatment, equivalent to Study Day 14 to 21) and follow-up (14 days after end of treatment, equivalent to Study Day 21 to 28)
Population: Carbapenem-resistant microbiological intention-to-treat population with SOFA measurement at Baseline and at each post-baseline time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Follow-up | -2.1 scores on a scale | Standard Deviation 4.4 |
| HAP/VAP/HCAP: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | End of treatment | -0.7 scores on a scale | Standard Deviation 3.6 |
| HAP/VAP/HCAP: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Test of cure | -1.3 scores on a scale | Standard Deviation 5 |
| HAP/VAP/HCAP: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Follow-up | -2.0 scores on a scale | Standard Deviation 2.9 |
| HAP/VAP/HCAP: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | End of treatment | -1.6 scores on a scale | Standard Deviation 2.6 |
| HAP/VAP/HCAP: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Test of cure | -1.7 scores on a scale | Standard Deviation 2.9 |
| BSI/Sepsis: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | End of treatment | -2.1 scores on a scale | Standard Deviation 3.7 |
| BSI/Sepsis: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Test of cure | -2.1 scores on a scale | Standard Deviation 2.5 |
| BSI/Sepsis: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Follow-up | -3.1 scores on a scale | Standard Deviation 3.1 |
| BSI/Sepsis: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | End of treatment | -0.2 scores on a scale | Standard Deviation 2.8 |
| BSI/Sepsis: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Follow-up | -0.2 scores on a scale | Standard Deviation 4.4 |
| BSI/Sepsis: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Test of cure | 0.2 scores on a scale | Standard Deviation 4.1 |
| cUTI: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Follow-up | -0.1 scores on a scale | Standard Deviation 2.5 |
| cUTI: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Test of cure | -0.6 scores on a scale | Standard Deviation 2 |
| cUTI: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | End of treatment | -0.6 scores on a scale | Standard Deviation 1.3 |
| cUTI: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Follow-up | -2.0 scores on a scale | Standard Deviation 3.5 |
| cUTI: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Test of cure | -1.3 scores on a scale | Standard Deviation 2.3 |
| cUTI: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | End of treatment | -1.3 scores on a scale | Standard Deviation 2.3 |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Follow-up | -1.9 scores on a scale | Standard Deviation 3.8 |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | End of treatment | -1.1 scores on a scale | Standard Deviation 3.3 |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Test of cure | -1.3 scores on a scale | Standard Deviation 3.8 |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Test of cure | -0.9 scores on a scale | Standard Deviation 3.4 |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | End of treatment | -1.0 scores on a scale | Standard Deviation 2.7 |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Change From Baseline in Sequential Organ Failure Assessment (SOFA) | Follow-up | -1.4 scores on a scale | Standard Deviation 3.5 |
Secondary
Number of Participants With Adverse Events
The severity of each adverse event (AE) was graded by the investigator according to the following definitions: * Mild: Symptom or finding is minor and does not interfere with usual daily activities * Moderate: The event causes discomfort and interferes with usual daily activity or affects clinical status * Severe: The event causes interruption of usual daily activities or has a clinically significant effect The relationship of AEs to study treatment was determined by the investigator according to the following definition: ● Related: An AE which can be reasonably explained as having been caused by the study treatment. A serious AE is defined as any AE that resulted in any of the following outcomes: * Death * Life-threatening condition * Hospitalization or prolongation of existing hospitalization * Persistent or significant disability/incapacity * Congenital anomaly/birth defect * Other medically important condition
Time frame: From first dose of study drug up to 28 days after last dose; maximum treatment duration was 29 days in the cefiderocol group and 22 days in the BAT group.
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Any adverse event (AE) | 92 Participants |
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Mild adverse events | 23 Participants |
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Moderate adverse events | 26 Participants |
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Severe adverse events | 43 Participants |
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Drug-related adverse events | 15 Participants |
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Discontinuations due to adverse events | 10 Participants |
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Discontinuations due to drug-related AEs | 3 Participants |
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Serious adverse events (SAE) | 50 Participants |
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Drug-related serious adverse events | 1 Participants |
| HAP/VAP/HCAP: Cefiderocol | Number of Participants With Adverse Events | Death due to serious adverse events | 34 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Serious adverse events (SAE) | 23 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Any adverse event (AE) | 47 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Discontinuations due to adverse events | 3 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Mild adverse events | 9 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Death due to serious adverse events | 9 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Moderate adverse events | 16 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Discontinuations due to drug-related AEs | 2 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Severe adverse events | 22 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Drug-related serious adverse events | 5 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Number of Participants With Adverse Events | Drug-related adverse events | 11 Participants |
Secondary
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
Population: Carbapenem-resistant Microbiological Intent-to-treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants Alive and With No Change in Antibiotic Treatment Due to Either Lack of Therapeutic Benefit or Drug-related Toxicity at TOC | 62.5 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants Alive and With No Change in Antibiotic Treatment Due to Either Lack of Therapeutic Benefit or Drug-related Toxicity at TOC | 60.5 percentage of participants |
Secondary
Percentage of Participants With a Composite Clinical and Microbiological Response at EOT
The composite clinical and microbiological response rate is defined as the percentage of participants with both clinical cure and microbiologic eradication, as defined above for each site of infection.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 30.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 26.3 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 56.5 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 21.4 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 70.6 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 20.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 39.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 24.2 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 46.3 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at EOT | 23.7 percentage of participants |
Secondary
Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up
The composite clinical and microbiological response rate is defined as the percentage of participants with both sustained clinical cure and sustained microbiologic eradication, as defined above for each site of infection.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 15.8 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 26.1 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 14.3 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 41.2 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 20.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 22.2 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 15.2 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 26.3 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up | 15.8 percentage of participants |
Secondary
Percentage of Participants With a Composite Clinical and Microbiological Response at TOC
The composite clinical and microbiological response rate is defined as the percentage of participants with both clinical cure and microbiologic eradication, as defined above for each site of infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 22.5 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 21.1 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 30.4 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 21.4 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 47.1 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 20.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 25.4 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 21.2 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 30.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With a Composite Clinical and Microbiological Response at TOC | 21.1 percentage of participants |
Secondary
Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis: HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 70.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Acinetobacter baumannii | 61.5 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 63.6 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Acinetobacter baumannii | 70.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Escherichia coli | 0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 40.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 83.3 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 63.6 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Acinetobacter baumannii | 70.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 100.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Acinetobacter baumannii | 42.9 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 75.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Acinetobacter baumannii | 0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 90.9 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Acinetobacter baumannii | 63.9 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 69.2 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 66.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Acinetobacter baumannii | 58.8 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 55.6 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Escherichia coli | 0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 75.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 64.7 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Acinetobacter baumannii | 62.2 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Pseudomonas aeruginosa | 63.6 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Escherichia coli | 0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Acinetobacter baumannii | 58.8 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen | Klebsiella pneumoniae | 58.3 percentage of participants |
Secondary
Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With cUTI
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered as non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With cUTI | 76.5 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With cUTI | 60.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 60.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 63.2 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 69.6 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 50.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 63.5 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 57.6 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 66.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 57.9 percentage of participants |
Secondary
Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis: HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 61.5 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 83.3 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 70.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 80.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 40.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 70.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 100.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 60.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 42.9 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 75.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 90.9 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 63.9 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 62.5 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 68.8 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 58.8 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 55.6 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 62.5 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 77.8 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 58.3 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 62.2 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 58.3 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 58.8 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 60.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 45.5 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Acinetobacter baumannii | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 60.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 40.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Acinetobacter baumannii | 60.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 66.7 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 54.5 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Acinetobacter baumannii | 30.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 100.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Acinetobacter baumannii | 42.9 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Acinetobacter baumannii | 0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 81.8 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Stenotrophomonas maltophilia | 5.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 53.8 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Acinetobacter baumannii | 44.4 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 57.1 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 55.6 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Acinetobacter baumannii | 52.9 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 44.4 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Acinetobacter baumannii | 43.2 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Escherichia coli | 60.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 52.9 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 65.6 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Pseudomonas aeruginosa | 54.5 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Acinetobacter baumannii | 52.9 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Cure at Test of Cure in Participants With cUTI
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure in Participants With cUTI | 70.6 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure in Participants With cUTI | 60.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 47.6 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 48.5 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 52.5 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 50.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis: HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 60.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 60.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 40.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 100.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 30.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 42.9 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 81.8 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 56.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 62.5 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 44.4 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 52.9 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 44.4 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 58.3 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 43.2 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 52.9 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen
Microbiological outcome per Baseline carbapenem-resistant pathogen were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 33.3 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 34.6 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 40.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 30.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 60.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 70.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 28.6 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 75.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 81.8 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 0.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 20. percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 25.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 41.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 56.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 37.5 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 22.2 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 29.4 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 40.5 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 40.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 16.7 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 29.4 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant Gram-negative pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 36.4 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Acinetobacter baumannii | 34.6 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Acinetobacter baumannii | 30.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Acinetobacter baumannii | 60.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 72.7 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 25.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Acinetobacter baumannii | 28.6 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 81.8 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Acinetobacter baumannii | 41.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 30.8 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 61.9 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Acinetobacter baumannii | 29.4 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 22.2 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 68.8 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 35.3 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Acinetobacter baumannii | 40.5 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Stenotrophomonas maltophilia | 20.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Acinetobacter baumannii | 29.4 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Pseudomonas aeruginosa | 36.4 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen | Klebsiella pneumoniae | 16.7 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at EOT in Participants With cUTI
Microbiological outcome per Baseline pathogen was determined by the sponsor as defined for each infection site. For cUTI eradication was defined as a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT in Participants With cUTI | 70.6 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT in Participants With cUTI | 20.0 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at EOT in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia
The percentage of participants who experienced eradication of the Baseline documented carbapenem-resistant Gram-negative bacteremia, defined as absence of the Baseline Gram-negative pathogen from a blood culture.
Time frame: End of treatment, Day 7 to 14
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia | 54.5 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia | 30.8 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 41.3 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 27.3 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 47.5 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 26.3 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria established for each infection site: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen (sputum, tracheal aspirate, bronchoalveolar lavage (BAL) fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: End of treatment, Day 7 to 14
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis | 30.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis | 26.3 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis | 60.9 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis | 28.6 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen
Microbiological outcome per Baseline carbapenem-resistant pathogen were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 30.8 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 0.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 30.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 20.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 20.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 28.6 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 25.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 72.7 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 0.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 31.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 27.8 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 33.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 12.5 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 29.4 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 8.3 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 48.1 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 27.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 29.4 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 25.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 20.0 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant Gram-negative pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 9.1 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Acinetobacter baumannii | 30.8 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Acinetobacter baumannii | 30.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 16.7 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 54.5 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Acinetobacter baumannii | 20.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Acinetobacter baumannii | 28.6 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 72.7 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 25.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 7.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 38.1 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Acinetobacter baumannii | 27.8 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Acinetobacter baumannii | 29.4 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 11.1 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 33.3 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Escherichia coli | 40.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 11.8 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Acinetobacter baumannii | 27.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Acinetobacter baumannii | 29.4 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Pseudomonas aeruginosa | 18.2 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Klebsiella pneumoniae | 25.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at TOC in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia
The percentage of participants who experienced eradication of the Baseline documented carbapenem-resistant Gram-negative bacteremia, defined as absence of the Baseline Gram-negative pathogen from a blood culture.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia | 31.8 percentge of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia | 30.8 percentge of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to \< 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 25.4 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 24.2 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 31.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 23.7 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis
Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria established for each infection site: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen (sputum, tracheal aspirate, bronchoalveolar lavage (BAL) fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.
Time frame: Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis | 22.5 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis | 21.1 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis | 30.4 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis | 28.6 percentage of participants |
Secondary
Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy was required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy was required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC. cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 40.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 40.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 100.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 30.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 40.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 25.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 28.6 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 63.6 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 25.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 44.4 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 62.5 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 33.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 35.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 25.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 43.2 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 55.6 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 30.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 35.3 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 41.7 percentage of participants |
Secondary
Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy was required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy was required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC. cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 50.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 60.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 45.5 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 60.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 16.7 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 40.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 45.5 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 30.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 100.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 33.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 28.6 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 25.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 25.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Escherichia coli | 100.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 63.6 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 66.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 44.4 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 53.8 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 52.4 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 35.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 33.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 55.6 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 47.1 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Escherichia coli | 60.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 56.3 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 43.2 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 41.7 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 27.3 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 35.3 percentage of participants |
Secondary
Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy was required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy was required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 50.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 31.6 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 39.1 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis | 28.6 percentage of participants |
Secondary
Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With cUTI
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population); participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With cUTI | 52.9 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With cUTI | 60.0 percentage of participants |
Secondary
Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy is required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy is required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC. cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 46.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 30.3 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 47.5 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 34.2 percentage of participants |
Secondary
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen
Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained \< 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant carbapenem-resistant pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 26.9 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 20.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 40.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 20.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 14.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 63.6 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 0.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 25.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 25.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 12.5 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 33.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 17.6 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 24.3 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 40.7 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Pseudomonas aeruginosa | 20.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Klebsiella pneumoniae | 25.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen | Acinetobacter baumannii | 17.6 percentage of participants |
Secondary
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen
Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained \< 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population with the relevant Gram-negative pathogen at Baseline; participants with missing data were considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 26.9 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 9.1 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 20.0 percentage of participants |
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 16.7 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 20.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 45.5 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 20.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 14.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 50.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 63.6 percentage of participants |
| cUTI: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 0.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 0.0 percentage of participants |
| cUTI: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Escherichia coli | 50.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 7.7 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 33.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 25.0 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 17.6 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 11.1 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 33.3 percentage of participants |
| HAP/VAP/HCAP + BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Stenotrophomonas maltophilia | 0.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Escherichia coli | 40.0 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 5.9 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 43.8 percentage of participants |
| Overall: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 24.3 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Acinetobacter baumannii | 17.6 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Pseudomonas aeruginosa | 18.2 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Klebsiella pneumoniae | 25.0 percentage of participants |
| Overall: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen | Escherichia coli | 0.0 percentage of participants |
Secondary
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With cUTI
Microbiological outcome per Baseline pathogen at follow-up was determined by the sponsor as defined for each infection site. For cUTI sustained eradication was defined as a culture taken any time after documented eradication at TOC and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained \<10³ CFU/mL. Overall per-participant sustained eradication was defined as sustained eradication of all Baseline Gram-negative pathogens.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With cUTI | 41.2 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With cUTI | 20.0 percentage of participants |
Secondary
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia
The percentage of participants who experienced sustained eradication of the Baseline documented carbapenem-resistant Gram-negative bacteremia, defined as absence of the Baseline Gram-negative pathogen from a blood culture after TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia | 27.3 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia | 23.1 percentage of participants |
Secondary
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall
Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained \< 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 22.2 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 18.2 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 26.3 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall | 18.4 percentage of participants |
Secondary
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis
Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. If an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For sepsis, if the participant has a successful clinical outcome after TOC and an appropriate clinical culture could not be obtained, the response was presumed sustained eradication. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.
Time frame: Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28
Population: Carbapenem-resistant Microbiological Intent-to-treat Population; participants with missing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis | 20.0 percentage of participants |
| HAP/VAP/HCAP: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis | 15.8 percentage of participants |
| BSI/Sepsis: Cefiderocol | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis | 26.1 percentage of participants |
| BSI/Sepsis: Best Available Therapy | Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis | 21.4 percentage of participants |
Secondary
Survival Time
Survival time was analyzed by Kaplan-Meier survival curve. The table below presents deaths that occurred in10-day time intervals through the end of study
Time frame: Days 1 to 10, 11 to 20, 21 to 30, 31 to 40, 41-50, and 51 to 60.
Population: Carbapenem-resistant Microbiological Intent-to-treat Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HAP/VAP/HCAP: Cefiderocol | Survival Time | Days 11 to 20 | 9 Participants |
| HAP/VAP/HCAP: Cefiderocol | Survival Time | Days 31 to 40 | 4 Participants |
| HAP/VAP/HCAP: Cefiderocol | Survival Time | Days 1 to 10 | 12 Participants |
| HAP/VAP/HCAP: Cefiderocol | Survival Time | Days 41 to 50 | 1 Participants |
| HAP/VAP/HCAP: Cefiderocol | Survival Time | Days 21 to 30 | 1 Participants |
| HAP/VAP/HCAP: Cefiderocol | Survival Time | Days 51 to 60 | 0 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Survival Time | Days 21 to 30 | 2 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Survival Time | Days 1 to 10 | 3 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Survival Time | Days 11 to 20 | 3 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Survival Time | Days 51 to 60 | 0 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Survival Time | Days 31 to 40 | 0 Participants |
| HAP/VAP/HCAP: Best Available Therapy | Survival Time | Days 41 to 50 | 0 Participants |