Urinary Tract Infections
Conditions
Keywords
S-649266, complicated urinary tract infection, cefiderocol, acute uncomplicated pyelonephritis, Gram-negative pathogens, imipenem/cilastatin
Brief summary
The purpose of this study was to determine the efficacy and safety of intravenous cefiderocol (S-649266) in hospitalized adults with complicated urinary tract infections caused by Gram-negative pathogens.
Interventions
DRUGCefiderocol
2000 mg intravenously every 8 hours for 7 to 14 days; dose adjustments for participants with reduced renal function (estimated CrCl ≤ 70 mL/minute) and/or body weight (\< 70 kg) included every 6-hour dosing intervals and/or reduced doses.
1000 mg of each intravenously every 8 hours for 7 to 14 days; dose adjustments for participants with reduced renal function (estimated CrCl ≤ 70 mL/minute) and/or body weight (\< 70 kg) included every 6-hour dosing intervals and/or reduced doses.
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hospitalized male and female patients ≥ 18 years * Clinical diagnosis of either complicated urinary tract infections (cUTI) with or without pyelonephritis or acute uncomplicated pyelonephritis * cUTI diagnosed with a history of ≥ 1 of the following: * Indwelling urinary catheter or recent instrumentation of the urinary tract * Urinary retention (caused by benign prostatic hypertrophy) * Urinary retention of at least 100 mL or more of residual urine after voiding (neurogenic bladder) * Obstructive uropathy * Azotemia caused by intrinsic renal disease (blood urea nitrogen and creatinine values greater than normal laboratory values) OR Pyelonephritis and normal urinary tract anatomy, ie, acute uncomplicated pyelonephritis AND At least 2 of the following signs or symptoms: * Chills or rigors or warmth associated with fever (temperature greater than or equal to 38 degrees Celsius) * Flank pain (pyelonephritis) or suprapubic/pelvic pain (cUTI) * Nausea or vomiting * Dysuria, urinary frequency, or urinary urgency * Costo-vertebral angle tenderness on physical examination AND All subjects had to have urinalysis evidence of pyuria demonstrated by 1 of the following: * Dipstick analysis positive for leukocyte esterase * ≥ 10 white blood cells (WBCs) per μL in unspun urine, or ≥ 10 WBCs per high power field in spun urine * Positive urine culture within 48 hours prior to randomization containing ≥10\^5 colony forming unit (CFU)/mL of a Gram-negative uropathogen likely to be susceptible to imipenem (IPM) * Patients who were treated previously with an empiric antibiotic other than the study drugs but failed treatment, both clinically and microbiologically, were eligible for the study if they had an identified Gram-negative uropathogen that was not susceptible to the previously used empiric treatment and likely to be susceptible to IPM * Subjects receiving antibiotic prophylaxis for UTI who present with signs and symptoms consistent with an active new UTI
Exclusion criteria
* Urine culture identifies only a Gram-positive pathogen and/or a Gram-negative uropathogen resistant to IPM * Urine culture at study entry isolates more than 2 uropathogens or patient has a confirmed fungal UTI * Asymptomatic bacteriuria, the presence of \>10\^5 CFU/mL of a uropathogen and pyuria but without local or systemic symptoms * Patient is receiving hemodialysis or peritoneal dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Test of Cure | Test of cure (TOC; 7 days after end of treatment [EOT], equivalent to Study Day 14 to 21) | The primary efficacy endpoint was the composite outcome of clinical response and microbiological response at the test of cure assessment, defined as 7 days (±2 days) after the end of antibiotic treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at End of Treatment | End of treatment (EOT; Day 7 to 14) | A composite outcome of clinical response and microbiological response at the end of treatment, defined as the end of the last infusion of antibiotic treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. |
| Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Follow-up | Follow-up (FUP; 14 days after end of treatment, Day 21 to 28) | A composite response of clinical response and microbiological response at the follow-up assessment, defined as 14 days after the end of treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with sustained response defined as all pre-therapy signs and symptoms of cUTI show no evidence of recurrence after administration of the last dose of study drug. Microbiological outcome was based on quantitative microbiological urine cultures, with sustained eradication defined as a urine culture obtained after documented eradication at the TOC, up to and including the FUP, showed that the bacterial uropathogen(s) identified at baseline at ≥ 10⁵ CFU/mL remained \< 10⁴ CFU/mL. |
| Percentage of Participants With Microbiological Eradication at Test of Cure | Test of cure (7 days after end of treatment, Day 14 to 21) | Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as all bacterial uropathogens found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. |
| Percentage of Participants With Microbiological Eradication at Early Assessment | Early assessment, Day 4 | Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as all bacterial uropathogens found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. |
| Percentage of Participants With Microbiological Eradication at End of Treatment | End of treatment, Day 7 to 14 | Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as all bacterial uropathogens found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. |
| Percentage of Participants With Microbiological Eradication at Follow-up | Follow-up, 14 days after end of treatment, Day 21 to 28 | Microbiological outcome was based on quantitative microbiological urine cultures, with sustained eradication defined as a urine culture obtained after documented eradication at the TOC, up to and including the FUP, where the bacterial uropathogen(s) identified at baseline at ≥ 10⁵ CFU/mL remained \< 10⁴ CFU/mL. |
| Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen | Test of cure; 7 days after end of treatment, Day 14 to 21 | Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. |
| Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen | Early assessment, Day 4 | Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. |
| Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen | End of treatment, Day 7 to 14 | Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. |
| Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen | Follow-up, 14 days after the end of treatment, Day 21 to 28 | Microbiological outcome was based on quantitative microbiological urine cultures, with sustained eradication defined as a urine culture obtained after documented eradication at the TOC, up to and including the FUP, where the bacterial uropathogen identified at baseline at ≥ 10⁵ CFU/mL remained \< 10⁴ CFU/mL. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. |
| Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Early Assessment | Early assessment (EA; Day 4) | A composite outcome of clinical response and microbiological response at the early assessment, defined as Day 4 of antibiotic treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. |
| Percentage of Participants With Clinical Response at Early Assessment | Early assessment, Day 4 | Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. |
| Percentage of Participants With Clinical Response at End of Treatment | End of treatment, Day 7 to 14 | Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. |
| Percentage of Participants With Clinical Response at Follow-up | Follow-up, 14 days after end of treatment, Day 21 to 28 | Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with sustained response defined as all pre-therapy signs and symptoms of cUTI showing no evidence of recurrence after administration of the last dose of study drug. |
| Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen | Test of cure, 7 days after end of treatment, Day 14 to 21 | Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. |
| Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen | Early assessment, Day 4 | Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. |
| Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen | End of treatment, Day 7 to 14 | Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. |
| Percentage of Participants With Clinical Response at Follow-up Per Uropathogen | Follow-up, 14 days after the end of treatment, Day 21 to 28 | Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with sustained response defined as all pre-therapy signs and symptoms of cUTI show no evidence of recurrence after administration of the last dose of study drug. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. |
| Plasma Concentration of Cefiderocol | On Day 3 of dosing prior to infusion, end of infusion, and at 1 hour post infusion | — |
| Urine Concentration of Cefiderocol | Day 3, 2 hours and 6 hours after end of infusion | — |
| Number of Participants With Adverse Events | From first dose of study drug until 28 days after end of treatment; Day 35 to 42 | A serious adverse event was defined by regulation as any adverse event (AE) occurring at any dose 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. The relationship of an event to the study drug was determined by the investigator based on whether the AE could be reasonably explained as being caused by the study drug. |
| Percentage of Participants With Clinical Response at Test of Cure | Test of cure, 7 days after end of treatment, Day 14 to 21 | Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. |
Participant flow
Recruitment details
This study was conducted at 67 hospitals in 15 countries. Participants diagnosed with complicated urinary tract infections (cUTIs) with or without pyelonephritis or acute uncomplicated pyelonephritis were enrolled from February 5, 2015 to August 16, 2016.
Pre-assignment details
Participants were randomly assigned (2:1) to receive either cefiderocol or imipenem-cilastatin. Randomization was stratified by clinical diagnosis (complicated urinary tract infection with or without pyelonephritis or with acute uncomplicated pyelonephritis) and region (North America, Europe, Russia, and Japan).
Participants by arm
| Arm | Count |
|---|---|
| Cefiderocol Participants received 2 g cefiderocol by intravenous injection once every 8 hours for 7 to 14 days. | 252 |
| Imipenem/Cilastatin Participants received 1 g each of imipenem/cilastatin by intravenous injection once every 8 hours for 7 to 14 days. | 119 |
| Total | 371 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 10 | 4 |
| Overall Study | Other, Miscellaneous | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Cefiderocol | Imipenem/Cilastatin | Total |
|---|---|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 16.1 | 61.3 years STANDARD_DEVIATION 18.48 | 62.0 years STANDARD_DEVIATION 16.88 |
| Age, Customized < 65 years | 113 Participants | 54 Participants | 167 Participants |
| Age, Customized >= 65 years | 139 Participants | 65 Participants | 204 Participants |
| Clinical Diagnosis at Baseline Acute Uncomplicated Pyelonephritis | 65 Participants | 35 Participants | 100 Participants |
| Clinical Diagnosis at Baseline cUTI without pyelonephritis | 122 Participants | 55 Participants | 177 Participants |
| Clinical Diagnosis at Baseline cUTI with pyelonephritis | 65 Participants | 29 Participants | 94 Participants |
| Creatinine Clearance Renal Grading Group 30 - 50 mL/min (Moderate) | 41 Participants | 23 Participants | 64 Participants |
| Creatinine Clearance Renal Grading Group < 30 mL/min (Severe) | 7 Participants | 4 Participants | 11 Participants |
| Creatinine Clearance Renal Grading Group > 50 - 80 mL/min (Mild) | 78 Participants | 41 Participants | 119 Participants |
| Creatinine Clearance Renal Grading Group > 80 mL/min (Normal) | 124 Participants | 51 Participants | 175 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 247 Participants | 118 Participants | 365 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of Gram-negative Uropathogens > 10⁵ CFU/mL Isolated at Baseline 1 uropathogen | 241 Participants | 115 Participants | 356 Participants |
| Number of Gram-negative Uropathogens > 10⁵ CFU/mL Isolated at Baseline 2 uropathogens | 11 Participants | 4 Participants | 15 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 4 Participants | 13 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 241 Participants | 115 Participants | 356 Participants |
| Sex: Female, Male Female | 133 Participants | 71 Participants | 204 Participants |
| Sex: Female, Male Male | 119 Participants | 48 Participants | 167 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 300 | 0 / 148 |
| other Total, other adverse events | 60 / 300 | 48 / 148 |
| serious Total, serious adverse events | 14 / 300 | 12 / 148 |
Outcome results
Primary
Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Test of Cure
The primary efficacy endpoint was the composite outcome of clinical response and microbiological response at the test of cure assessment, defined as 7 days (±2 days) after the end of antibiotic treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Time frame: Test of cure (TOC; 7 days after end of treatment [EOT], equivalent to Study Day 14 to 21)
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Test of Cure | 72.6 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Test of Cure | 54.6 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [8.23, 28.92]
Secondary
Number of Participants With Adverse Events
A serious adverse event was defined by regulation as any adverse event (AE) occurring at any dose 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. The relationship of an event to the study drug was determined by the investigator based on whether the AE could be reasonably explained as being caused by the study drug.
Time frame: From first dose of study drug until 28 days after end of treatment; Day 35 to 42
Population: The safety population included all randomized participants who received at least 1 dose of the study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cefiderocol | Number of Participants With Adverse Events | All adverse events | 122 Participants |
| Cefiderocol | Number of Participants With Adverse Events | Drug-related adverse events | 27 Participants |
| Cefiderocol | Number of Participants With Adverse Events | Discontinuation of study drug due to AE | 5 Participants |
| Cefiderocol | Number of Participants With Adverse Events | Discontinuation due to drug-related AE | 3 Participants |
| Cefiderocol | Number of Participants With Adverse Events | Deaths | 1 Participants |
| Cefiderocol | Number of Participants With Adverse Events | Serious adverse events | 14 Participants |
| Cefiderocol | Number of Participants With Adverse Events | Drug-related serious adverse events | 1 Participants |
| Imipenem/Cilastatin | Number of Participants With Adverse Events | Discontinuation due to drug-related AE | 0 Participants |
| Imipenem/Cilastatin | Number of Participants With Adverse Events | All adverse events | 76 Participants |
| Imipenem/Cilastatin | Number of Participants With Adverse Events | Drug-related adverse events | 17 Participants |
| Imipenem/Cilastatin | Number of Participants With Adverse Events | Drug-related serious adverse events | 1 Participants |
| Imipenem/Cilastatin | Number of Participants With Adverse Events | Serious adverse events | 12 Participants |
| Imipenem/Cilastatin | Number of Participants With Adverse Events | Discontinuation of study drug due to AE | 3 Participants |
| Imipenem/Cilastatin | Number of Participants With Adverse Events | Deaths | 0 Participants |
Secondary
Percentage of Participants With Clinical Response at Early Assessment
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms.
Time frame: Early assessment, Day 4
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Clinical Response at Early Assessment | 90.5 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Early Assessment | 90.8 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [-6.57, 6.05]
Secondary
Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Time frame: Early assessment, Day 4
Population: Modified intent-to-treat population with the relevant pathogen at Baseline and with available clinical outcome data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cefiderocol | Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen | Pseudomonas aeruginosa | 93.3 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen | Escherichia coli | 91.8 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen | Proteus mirabilis | 84.6 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen | Klebsiella pneumoniae | 82.6 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen | Proteus mirabilis | 100.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen | Klebsiella pneumoniae | 88.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen | Escherichia coli | 96.1 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen | Pseudomonas aeruginosa | 75.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Response at End of Treatment
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms.
Time frame: End of treatment, Day 7 to 14
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Clinical Response at End of Treatment | 98.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at End of Treatment | 99.2 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [-3.42, 1.29]
Secondary
Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Time frame: End of treatment, Day 7 to 14
Population: Modified intent-to-treat population with the relevant pathogen at Baseline and with available clinical outcome data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cefiderocol | Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen | Klebsiella pneumoniae | 100.0 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen | Proteus mirabilis | 100.0 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen | Pseudomonas aeruginosa | 93.3 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen | Escherichia coli | 97.9 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen | Klebsiella pneumoniae | 100.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen | Escherichia coli | 98.7 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen | Pseudomonas aeruginosa | 100.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen | Proteus mirabilis | 100.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Response at Follow-up
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with sustained response defined as all pre-therapy signs and symptoms of cUTI showing no evidence of recurrence after administration of the last dose of study drug.
Time frame: Follow-up, 14 days after end of treatment, Day 21 to 28
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Clinical Response at Follow-up | 81.3 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Follow-up | 72.3 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [-0.37, 18.41]
Secondary
Percentage of Participants With Clinical Response at Follow-up Per Uropathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with sustained response defined as all pre-therapy signs and symptoms of cUTI show no evidence of recurrence after administration of the last dose of study drug. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Time frame: Follow-up, 14 days after the end of treatment, Day 21 to 28
Population: Modified intent-to-treat population with the relevant pathogen at Baseline and with available clinical outcome data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cefiderocol | Percentage of Participants With Clinical Response at Follow-up Per Uropathogen | Escherichia coli | 82.9 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at Follow-up Per Uropathogen | Proteus mirabilis | 84.6 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at Follow-up Per Uropathogen | Pseudomonas aeruginosa | 53.3 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at Follow-up Per Uropathogen | Klebsiella pneumoniae | 82.6 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Follow-up Per Uropathogen | Pseudomonas aeruginosa | 75.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Follow-up Per Uropathogen | Proteus mirabilis | 100.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Follow-up Per Uropathogen | Klebsiella pneumoniae | 68.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Follow-up Per Uropathogen | Escherichia coli | 72.7 percentage of participants |
Secondary
Percentage of Participants With Clinical Response at Test of Cure
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms.
Time frame: Test of cure, 7 days after end of treatment, Day 14 to 21
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Clinical Response at Test of Cure | 89.7 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Test of Cure | 87.4 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [-4.66, 9.44]
Secondary
Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Time frame: Test of cure, 7 days after end of treatment, Day 14 to 21
Population: Modified intent-to-treat population with the relevant pathogen at Baseline and available clinical outcome data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cefiderocol | Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen | Escherichia coli | 89.7 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen | Klebsiella pneumoniae | 89.1 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen | Pseudomonas aeruginosa | 73.3 percentage of participants |
| Cefiderocol | Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen | Proteus mirabilis | 100.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen | Proteus mirabilis | 100.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen | Escherichia coli | 88.3 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen | Pseudomonas aeruginosa | 75.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen | Klebsiella pneumoniae | 84.0 percentage of participants |
Secondary
Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Early Assessment
A composite outcome of clinical response and microbiological response at the early assessment, defined as Day 4 of antibiotic treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Time frame: Early assessment (EA; Day 4)
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Early Assessment | 88.1 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Early Assessment | 87.4 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [-6.48, 7.79]
Secondary
Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at End of Treatment
A composite outcome of clinical response and microbiological response at the end of treatment, defined as the end of the last infusion of antibiotic treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Time frame: End of treatment (EOT; Day 7 to 14)
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at End of Treatment | 96.4 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at End of Treatment | 95.8 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [-3.48, 4.92]
Secondary
Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Follow-up
A composite response of clinical response and microbiological response at the follow-up assessment, defined as 14 days after the end of treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with sustained response defined as all pre-therapy signs and symptoms of cUTI show no evidence of recurrence after administration of the last dose of study drug. Microbiological outcome was based on quantitative microbiological urine cultures, with sustained eradication defined as a urine culture obtained after documented eradication at the TOC, up to and including the FUP, showed that the bacterial uropathogen(s) identified at baseline at ≥ 10⁵ CFU/mL remained \< 10⁴ CFU/mL.
Time frame: Follow-up (FUP; 14 days after end of treatment, Day 21 to 28)
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Follow-up | 54.4 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Follow-up | 39.5 percentage of participants |
95% CI: [4.69, 25.92]
Secondary
Percentage of Participants With Microbiological Eradication at Early Assessment
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as all bacterial uropathogens found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Time frame: Early assessment, Day 4
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Early Assessment | 92.1 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Early Assessment | 90.8 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [-4.83, 7.39]
Secondary
Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Time frame: Early assessment, Day 4
Population: Intent-to-treat population with the relevant pathogen at Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen | Escherichia coli | 92.8 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen | Proteus mirabilis | 88.2 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen | Klebsiella pneumoniae | 89.6 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen | Pseudomonas aeruginosa | 94.4 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen | Pseudomonas aeruginosa | 80.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen | Escherichia coli | 94.9 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen | Klebsiella pneumoniae | 88.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen | Proteus mirabilis | 100.0 percentage of participants |
Secondary
Percentage of Participants With Microbiological Eradication at End of Treatment
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as all bacterial uropathogens found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Time frame: End of treatment, Day 7 to 14
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Microbiological Eradication at End of Treatment | 96.8 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at End of Treatment | 95.8 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [-3.04, 5.25]
Secondary
Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Time frame: End of treatment, Day 7 to 14
Population: Modified intent-to-treat population with the relevant pathogen at Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cefiderocol | Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen | Escherichia coli | 98.7 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen | Klebsiella pneumoniae | 97.9 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen | Pseudomonas aeruginosa | 88.9 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen | Proteus mirabilis | 94.1 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen | Proteus mirabilis | 100.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen | Escherichia coli | 97.5 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen | Pseudomonas aeruginosa | 100.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen | Klebsiella pneumoniae | 92.0 percentage of participants |
Secondary
Percentage of Participants With Microbiological Eradication at Follow-up
Microbiological outcome was based on quantitative microbiological urine cultures, with sustained eradication defined as a urine culture obtained after documented eradication at the TOC, up to and including the FUP, where the bacterial uropathogen(s) identified at baseline at ≥ 10⁵ CFU/mL remained \< 10⁴ CFU/mL.
Time frame: Follow-up, 14 days after end of treatment, Day 21 to 28
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Follow-up | 57.1 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Follow-up | 43.7 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [3.21, 24.63]
Secondary
Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen
Microbiological outcome was based on quantitative microbiological urine cultures, with sustained eradication defined as a urine culture obtained after documented eradication at the TOC, up to and including the FUP, where the bacterial uropathogen identified at baseline at ≥ 10⁵ CFU/mL remained \< 10⁴ CFU/mL. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Time frame: Follow-up, 14 days after the end of treatment, Day 21 to 28
Population: Modified intent-to-treat population with the relevant pathogen at Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen | Escherichia coli | 59.9 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen | Pseudomonas aeruginosa | 27.8 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen | Klebsiella pneumoniae | 58.3 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen | Proteus mirabilis | 64.7 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen | Klebsiella pneumoniae | 52.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen | Escherichia coli | 41.8 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen | Proteus mirabilis | 0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen | Pseudomonas aeruginosa | 20.0 percentage of participants |
Secondary
Percentage of Participants With Microbiological Eradication at Test of Cure
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as all bacterial uropathogens found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Time frame: Test of cure (7 days after end of treatment, Day 14 to 21)
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Test of Cure | 73.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Test of Cure | 56.3 percentage of participants |
Comparison: Adjusted estimates of the difference between the two treatment groups are based on a stratified analysis using Cochran-Mantel-Haenszel weights, with clinical diagnosis (complicated urinary tract infection with or without pyelonephritis vs acute uncomplicated pyelonephritis) as the stratification factor.95% CI: [6.92, 27.58]
Secondary
Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Time frame: Test of cure; 7 days after end of treatment, Day 14 to 21
Population: Modified intent-to-treat population with the relevant pathogen at Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen | Escherichia coli | 75.0 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen | Pseudomonas aeruginosa | 44.4 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen | Klebsiella pneumoniae | 75.0 percentage of participants |
| Cefiderocol | Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen | Proteus mirabilis | 76.5 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen | Klebsiella pneumoniae | 52.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen | Escherichia coli | 58.2 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen | Proteus mirabilis | 50.0 percentage of participants |
| Imipenem/Cilastatin | Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen | Pseudomonas aeruginosa | 60.0 percentage of participants |
Secondary
Plasma Concentration of Cefiderocol
Time frame: On Day 3 of dosing prior to infusion, end of infusion, and at 1 hour post infusion
Population: The pharmacokinetic (PK) concentration population included all participants who underwent plasma or urine PK sampling and had at least 1 evaluable PK assay result for cefiderocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cefiderocol | Plasma Concentration of Cefiderocol | End of infusion | 141 µg/mL | Standard Deviation 220 |
| Cefiderocol | Plasma Concentration of Cefiderocol | Pre-infusion | 18.0 µg/mL | Standard Deviation 18.3 |
| Cefiderocol | Plasma Concentration of Cefiderocol | 1 hour after end of infusion | 70.2 µg/mL | Standard Deviation 30.4 |
Secondary
Urine Concentration of Cefiderocol
Time frame: Day 3, 2 hours and 6 hours after end of infusion
Population: Pharmacokinetic concentration population with available urine concentration data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cefiderocol | Urine Concentration of Cefiderocol | 2 hours after end of infusion | 2710 µg/mL | Standard Deviation 1520 |
| Cefiderocol | Urine Concentration of Cefiderocol | 6 hours after end of infusion | 1520 µg/mL | Standard Deviation 1370 |