Clinical Study of Cefiderocol (S-649266) for the Treatmen... | NCT03032380

NCT03032380

ID	Type	Description	Link
2016-003020-23	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cefiderocol	Experimental	Participants will receive 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.	Drug: Cefiderocol Drug: Linezolid
Meropenem	Active Comparator	Participants will receive 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.	Drug: Meropenem Drug: Linezolid

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cefiderocol	Drug	2000 mg intravenously every 8 hours for a period of 7 to14 days (dosage adjustment is necessary based on renal function)	Cefiderocol

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
All-cause Mortality Rate at Day 14	The all-cause mortality (ACM) rate at Day 14 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from the first infusion of study drug up to Day 14. The Modified Intent-to-Treat Population included all randomized participants who met either of the following criteria: Evidence of Gram-negative infection of the lower respiratory tract based on a culture, Gram-stain, or other diagnostic test Evidence of a lower respiratory tract infection but culture or other diagnostic tests did not provide a microbiologic diagnosis	From first dose of study drug to Day 14

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Microbiologic Eradication at Test of Cure (TOC)	Lower respiratory tract specimens (eg, sputum, endotracheal aspiration [ETA], endobronchial culture specimens collected by bronchoalveolar lavage [BAL], or protected specimen brush [PSB], lung biopsy tissue, pleural effusions, etc) were sent to the local microbiology laboratory for isolation and identification of pathogens. Microbiological outcome by Baseline pathogen at TOC was determined by the sponsor as either Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen. Eradication: Absence of all Baseline Gram-negative pathogens 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 as eradication.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects 18 years or older at the time of signing informed consent
Subjects who have provided written informed consent or their informed consent has been provided by a legally authorized representative
Subjects who meet the clinical diagnosis criteria for hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or healthcare-associated bacterial pneumonia (HCABP)
All subjects must fulfill at least 1 of the following clinical criteria at screening:
1. New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea, tachypnea (eg, respiratory rate > 25 breaths/minute), expectorated sputum production, or requirement for mechanical ventilation
2. Hypoxemia (eg, a partial pressure of oxygen [PaO2] < 60 mm Hg while the subject is breathing room air, as determined by arterial blood gas [ABG], or worsening of the ratio of the PaO2 to the fraction of inspired oxygen [PaO2/FiO2])
3. Need for acute changes in the ventilator support system to enhance oxygenation, as determined by worsening oxygenation (ABG or PaO2/FiO2) or needed changes in the amount of positive end-expiratory pressure
4. New onset of or increase in (quantity or characteristics) suctioned respiratory secretions, demonstrating evidence of inflammation and absence of contamination
All subjects must have at least 1 of the following signs:
1. Documented fever (ie, core body temperature [tympanic, rectal, esophageal] ≥ 38°C [100.4°F], oral temperature ≥ 37.5°C, or axillary temperature ≥ 37°C)
2. Hypothermia (ie, core body temperature [tympanic, rectal, esophageal] ≤ 35°C [95.0°F], oral temperature ≤ 35.5°C and axillary temperature ≤ 36°C)
3. Leukocytosis with a total peripheral white blood cell (WBC) count ≥ 10,000 cells/mm³
4. Leukopenia with total peripheral WBC count ≤ 4500 cells/mm³
5. Greater than 15% immature neutrophils (bands) noted on peripheral blood smear
All subjects must have a chest radiograph during screening showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia. A computed tomography (CT) scan in the same time window showing the same findings could also be acceptable
All subjects must have a suspected Gram-negative infection involving the lower respiratory tract

Exclusion Criteria:

Subjects who have known or suspected community-acquired bacterial pneumonia (CABP), atypical pneumonia, viral pneumonia, or chemical pneumonia (including aspiration of gastric contents, inhalation injury)
Other exclusions based on the prescribing information of meropenem or linezolid, prior antibiotic usage, age, and pregnancy.

Name	Affiliation	Role
Shionogi Clinical Trials Administrator Clinical Support Help Line	Shionogi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Shionogi Research Site		New Haven	Connecticut	06511	United States
Shionogi Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35076335	Derived	Nordmann P, Shields RK, Doi Y, Takemura M, Echols R, Matsunaga Y, Yamano Y. Mechanisms of Reduced Susceptibility to Cefiderocol Among Isolates from the CREDIBLE-CR and APEKS-NP Clinical Trials. Microb Drug Resist. 2022 Apr;28(4):398-407. doi: 10.1089/mdr.2021.0180. Epub 2022 Jan 24.
35025025	Derived	Skaar EP, Echols R, Matsunaga Y, Menon A, Portsmouth S. Iron serum levels and iron homeostasis parameters in patients with nosocomial pneumonia treated with cefiderocol: post hoc analysis of the APEKS-NP study. Eur J Clin Microbiol Infect Dis. 2022 Mar;41(3):467-476. doi: 10.1007/s10096-021-04399-9. Epub 2022 Jan 13.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
FG001	Meropenem

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Jul 9, 2019	Oct 19, 2020

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00064.7± 14.5 BG00165.6± 15.1 BG00265.2± 14.8

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 65 years	BG00065 BG00158 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00047 BG00146 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0004 BG0013 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
White	BG000102 BG001100 BG002

Region

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
North America	BG0006 BG0016 BG002

Clinical Diagnosis

HABP = hospital acquired bacterial pneumonia; HCABP = healthcare-associated bacterial pneumonia; VABP = ventilator-associated bacterial pneumonia

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
VABP	BG00060 BG00165

Acute Physiology and Chronic Health Evaluation II (APACHE II) Score

Acute Physiology And Chronic Health Evaluation II is a severity-of-disease classification applied within 24 hours of admission of a patient to an intensive care unit (ICU). The APACHE II score consists of three parts: 12 acute physiological variables, age, and chronic health status. The range of the score is 0 to 71, where higher scores correspond to more severe disease and a higher risk of death.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<= 15	BG00075 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

All-cause Mortality Rate at Day 14

The all-cause mortality (ACM) rate at Day 14 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from the first infusion of study drug up to Day 14.

The Modified Intent-to-Treat Population included all randomized participants who met either of the following criteria:

Evidence of Gram-negative infection of the lower respiratory tract based on a culture, Gram-stain, or other diagnostic test
Evidence of a lower respiratory tract infection but culture or other diagnostic tests did not provide a microbiologic diagnosis

Modified Intent-to-Treat Population; participants with known survival status.

Posted

Number

percentage of participants

From first dose of study drug to Day 14

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Units	Counts
Participants	OG000145 OG001146

Title

Denominators

Categories

Title	Measurements
	OG00012.4 OG00111.6

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		0.0020		Treatment Difference	0.8			2-Sided	95	-6.6	8.2			Treatment difference (cefiderocol - meropenem) was the adjusted estimate of the difference in the ACM rate at Day 14 based on Cochran-Mantel Haenszel weights using APACHE II score (≤ 15 and ≥ 16) as the stratification factor.		Non-Inferiority	The study hypothesis was that the all-cause mortality rate at Day 14 in participants who received cefiderocol would be non-inferior to that in participants who received high-dose meropenem. The margin of non-inferiority was 12.5%. Non-inferiority was concluded if the upper bound of the 2-sided 95% confidence interval for the difference in mortality at Day 14 between the 2 treatment groups (cefiderocol - meropenem) was smaller than 12.5%.

Secondary

Percentage of Participants With Microbiologic Eradication at Test of Cure (TOC)

Lower respiratory tract specimens (eg, sputum, endotracheal aspiration [ETA], endobronchial culture specimens collected by bronchoalveolar lavage [BAL], or protected specimen brush [PSB], lung biopsy tissue, pleural effusions, etc) were sent to the local microbiology laboratory for isolation and identification of pathogens.

Microbiological outcome by Baseline pathogen at TOC was determined by the sponsor as either Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen.

Eradication: Absence of all Baseline Gram-negative pathogens 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 as eradication.

Modified Intent-to-Treat Population; participants with non-missing Baseline pathogen data

Posted

Number

percentage of participants

Test of cure (7 days after end of treatment; equivalent to Study Day 14 to 21)

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem

Secondary

Percentage of Participants With Clinical Cure at Test of Cure

Clinical outcome was assessed by the investigator as either Clinical Cure, Clinical Failure, or Indeterminate.

Clinical Cure: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia, including a reduction in Sequential Organ Failure Assessment (SOFA) and Clinical Pulmonary Infection Score (CPIS) scores, and improvement or lack of progression of chest radiographic abnormalities such that no additional antibacterial therapy was required for the treatment of the current infection.

Modified Intent-to-Treat Population

Posted

Number

percentage of participants

Test of cure (7 days after the end of treatment; equivalent to Study Day 14 to 21)

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Units	Counts

Secondary

Percentage of Participants With Clinical Cure at Early Assessment (EA)

Clinical outcome was assessed by the investigator as either Clinical Cure, Clinical Failure, or Indeterminate.

Modified Intent-to-Treat Population

Posted

Number

percentage of participants

Early assessment (Day 3-4 after the start of treatment)

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Units	Counts

Secondary

Percentage of Participants With Clinical Cure at End of Treatment (EOT)

Clinical outcome was assessed by the investigator as either Clinical Cure, Clinical Failure, or Indeterminate.

Modified Intent-to-Treat Population

Posted

Number

percentage of participants

End of treatment (Day 7 to 14)

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Units	Counts

Secondary

Percentage of Participants With Sustained Clinical Cure at Follow-up (FU)

Clinical outcome was assessed by the investigator at follow-up as either Sustained Clinical Cure, Relapse, or Indeterminate.

Sustained Clinical Cure: 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.

Modified Intent-to-Treat Population

Posted

Number

percentage of participants

Follow-up (14 days after the end of treatment; Day 21 to 28)

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Units	Counts
Participants

Secondary

Percentage of Participants With Microbiologic Eradication at Early Assessment

Microbiological outcome by Baseline pathogen at Early Assessment was determined by the sponsor as either Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen.

Eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, 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 as eradication.

Modified Intent-to-Treat Population; participants with non-missing Baseline pathogens

Posted

Number

percentage of participants

Early Assessment, Days 3 to 4

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Secondary

Percentage of Participants With Microbiologic Eradication at End of Treatment

Microbiological outcome by Baseline pathogen at End of Treatment was determined by the sponsor as either: Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen.

Modified Intent to-Treat Population; participants with non-missing Baseline pathogens

Posted

Number

percentage of participants

End of treatment, Day 7 to 14

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Secondary

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up

Microbiological outcome by Baseline pathogen at Follow-up was determined by the sponsor as either Sustained Eradication, Persistence, Recurrence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen.

Sustained eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, BAL fluid, protected specimen brush, pleural fluid, or lung biopsy) after TOC. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical response after TOC, the response was presumed to be eradication.

Modified Intent-to-Treat Population; participants with non-missing Baseline pathogens

Posted

Number

percentage of participants

Follow-up (14 days after the end of treatment, Days 21 to 28)

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Secondary

All-cause Mortality Rate at Day 28

The all-cause mortality (ACM) rate at Day 28 was calculated as the percentage of participants who experienced mortality, regardless of the cause, from the first dose of study drug up to Day 28.

Modified Intent-to-Treat Population; participants with known survival status.

Posted

Number

percentage of participants

From first dose of study drug to Day 28

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Units	Counts
Participants	OG000

Secondary

All-cause Mortality Rate at the End of Study

The all-cause mortality rate during both the treatment and follow-up period (up to the end of study [EOS] visit) was calculated as the percentage of participants who experienced mortality, regardless of the cause, from the first infusion of study drug up to EOS. If a participant discontinued from the study before EOS and survival information was not available, then the survival status for this endpoint for the participant was considered unknown.

Modified Intent-to-Treat Population; participants with known survival status.

Posted

Number

percentage of participants

From first dose of study drug through end of study (28 days after end of treatment, up to 42 days)

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Units	Counts

Secondary

Total Hospitalization Time

The length of hospital stay attributable to the study-qualifying infection.

Modified Intent-to-Treat Population

Posted

Mean

Standard Deviation

days

From first dose of study drug to test of cure (7 days after end of treatment; equivalent to Study Day 14 to 21) and to follow-up (14 days after the end of treatment; Day 21 to 28)

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Treatment-Emergent Adverse Events

The severity of each adverse event (AE) was graded by the investigator according to the following definitions:

Mild: A finding or symptom 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 an interruption of the participant's usual daily activities or has a clinically significant effect.

The relationship of each AE to the study treatment was determined by the investigator based on whether the AE could be reasonably explained as having been caused by the study drug (treatment related AE [TRAE]).

An SAE is defined as any AE occurring at any dose that resulted in any of the following outcomes:

Death
Life-threatening condition
Hospitalization or prolongation of existing hospitalization for treatment
Persistent or significant disability/incapacity
Congenital anomaly/birth defect
Other medically important condition

The safety population included all randomized participants who received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

From first dose of study drug through the end of study, up to 42 days.

ID	Title	Description
OG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
OG001	Meropenem

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coagulopathy	Blood and lymphatic system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0012 affected150 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Haemorrhagic anaemia	Blood and lymphatic system disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0012 affected150 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0012 affected150 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0010 affected150 at risk
Cardiac arrest	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0007 affected148 at risk EG0015 affected150 at risk
Cardiac failure	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0013 affected150 at risk
Cardiac failure acute	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0012 affected150 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0012 affected150 at risk
Cardiogenic shock	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Cardiovascular disorder	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Cardiovascular insufficiency	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0011 affected150 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0010 affected150 at risk
Myocardial infarction	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Abdominal wall haematoma	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Acute abdomen	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Intestinal infarction	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Death	General disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0011 affected150 at risk
General physical health deterioration	General disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0014 affected150 at risk
Sudden death	General disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Hepatocellular injury	Hepatobiliary disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Acinetobacter bacteraemia	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Bacteraemia	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Bacterial sepsis	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Brain abscess	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Herpes zoster	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Lung infection	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Meningitis	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Meningoencephalitis bacterial	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Pneumonia	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0006 affected148 at risk EG0013 affected150 at risk
Pneumonia bacterial	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Pneumonia necrotising	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Pseudomonas infection	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Sepsis	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0012 affected150 at risk
Septic encephalopathy	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Septic shock	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0011 affected150 at risk
Spinal cord infection	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Systemic candida	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Urinary tract infection	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0012 affected150 at risk
Splenic rupture	Injury, poisoning and procedural complications	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Subarachnoid haemorrhage	Injury, poisoning and procedural complications	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Alanine aminotransferase increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Aspartate aminotransferase increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0011 affected150 at risk
Blood pressure increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Hepatic enzyme increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0015 affected150 at risk
Liver function test abnormal	Investigations	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Liver function test increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0010 affected150 at risk
Transaminases increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0011 affected150 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Autonomic nervous system imbalance	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Brain injury	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Brain oedema	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0015 affected150 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0011 affected150 at risk
Encephalopathy	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Hypoxic-ischaemic encephalopathy	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0011 affected150 at risk
Lacunar stroke	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0011 affected150 at risk
Status epilepticus	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Stroke in evolution	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0013 affected150 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0006 affected148 at risk EG0011 affected150 at risk
Bronchopleural fistula	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0011 affected150 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0012 affected150 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Pulmonary artery thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0013 affected150 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0011 affected150 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0010 affected150 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0013 affected150 at risk
Stridor	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Leg amputation	Surgical and medical procedures	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Femoral artery embolism	Vascular disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Hypotension	Vascular disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Hypovolaemic shock	Vascular disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0010 affected150 at risk
Shock haemorrhagic	Vascular disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0011 affected150 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 18.1	Systematic Assessment	EG00012 affected148 at risk EG00112 affected150 at risk
Thrombocytosis	Blood and lymphatic system disorders	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0013 affected150 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0010 affected150 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0016 affected150 at risk
Atrial fibrillation	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0007 affected148 at risk EG0014 affected150 at risk
Bradycardia	Cardiac disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0012 affected150 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG00013 affected148 at risk EG00113 affected150 at risk
Constipation	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG0007 affected148 at risk EG0016 affected150 at risk
Nausea	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0012 affected150 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0014 affected150 at risk
Pyrexia	General disorders	MedDRA version 18.1	Systematic Assessment	EG0005 affected148 at risk EG0015 affected150 at risk
Oedema peripheral	General disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0013 affected150 at risk
Hepatocellular injury	Hepatobiliary disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0013 affected150 at risk
Urinary tract infection	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG00022 affected148 at risk EG00115 affected150 at risk
Pneumonia	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0005 affected148 at risk EG0015 affected150 at risk
Clostridium difficile infection	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0013 affected150 at risk
Urinary tract infection fungal	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0012 affected150 at risk
Tracheobronchitis	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0014 affected150 at risk
Bronchitis	Infections and infestations	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0013 affected150 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0011 affected150 at risk
Aspartate aminotransferase increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0009 affected148 at risk EG0015 affected150 at risk
Alanine aminotransferase increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0008 affected148 at risk EG0016 affected150 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0005 affected148 at risk EG0012 affected150 at risk
Transaminases increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0013 affected150 at risk
Hepatic enzyme increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0015 affected150 at risk
Amylase increased	Investigations	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0010 affected150 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG00016 affected148 at risk EG00123 affected150 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0008 affected148 at risk EG0011 affected150 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0006 affected148 at risk EG0013 affected150 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0005 affected148 at risk EG0018 affected150 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG00110 affected150 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0012 affected150 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0011 affected150 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG0010 affected150 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0014 affected150 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0011 affected150 at risk
Gout	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0013 affected150 at risk
Metabolic alkalosis	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0013 affected150 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA version 18.1	Systematic Assessment	EG0000 affected148 at risk EG0014 affected150 at risk
Headache	Nervous system disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0011 affected150 at risk
Delirium	Psychiatric disorders	MedDRA version 18.1	Systematic Assessment	EG0005 affected148 at risk EG0014 affected150 at risk
Insomnia	Psychiatric disorders	MedDRA version 18.1	Systematic Assessment	EG0005 affected148 at risk EG0013 affected150 at risk
Anxiety	Psychiatric disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0010 affected150 at risk
Agitation	Psychiatric disorders	MedDRA version 18.1	Systematic Assessment	EG0001 affected148 at risk EG0013 affected150 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0009 affected148 at risk EG0015 affected150 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0005 affected148 at risk EG0016 affected150 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0013 affected150 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA version 18.1	Systematic Assessment	EG0004 affected148 at risk EG00110 affected150 at risk
Hypertension	Vascular disorders	MedDRA version 18.1	Systematic Assessment	EG0005 affected148 at risk EG0017 affected150 at risk
Phlebitis	Vascular disorders	MedDRA version 18.1	Systematic Assessment	EG0003 affected148 at risk EG0014 affected150 at risk
Hypotension	Vascular disorders	MedDRA version 18.1	Systematic Assessment	EG0002 affected148 at risk EG0019 affected150 at risk

ID	Term
D000077299	Healthcare-Associated Pneumonia
D053717	Pneumonia, Ventilator-Associated
D011014	Pneumonia

ID	Term
D003428	Cross Infection
D007239	Infections
D012141	Respiratory Tract Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D007049	Iatrogenic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D002511	Cephalosporins
D047090	beta-Lactams
D007769	Lactams
D000577	Amides
D009930	Organic Chemicals
D013843	Thiazines
D013457	Sulfur Compounds
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D013845	Thienamycins
D015780	Carbapenems
D000081	Acetamides
D000085	Acetates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D023303	Oxazolidinones
D010080	Oxazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description
BG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
BG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cefiderocol	Participants received 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.	39	148	54	148	119	148
EG001	Meropenem	Participants received 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.	35	150	45	150	123	150