Ceftobiprole in the Treatment of Patients With Staphyloco... | NCT03138733

Name	Class
Department of Health and Human Services	FED

Label	Type	Description	Intervention Names
Ceftobiprole medocaril	Experimental	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril)	Drug: Ceftobiprole medocaril
Daptomycin	Active Comparator	Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards), with or without aztreonam	Drug: Daptomycin

Name	Type	Description	Arm Group Labels	Other Names
Ceftobiprole medocaril	Drug	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) as a 2 h infusion	Ceftobiprole medocaril

Measure	Description	Time Frame
Number of Patients With or Without Overall Success at the Post-treatment Evaluation (PTE) Visit	Comparison of overall success rates in the mITT population Overall success at PTE for the mITT population was defined as all of the following criteria being met (Responder): Patient alive at Day 70 (± 5 days) post-randomization. No new metastatic foci or complications of the SAB infection. Resolution or improvement of SAB-related clinical signs and symptoms. Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus)	PTE visit on Day 70 (± 5 days) post-randomization

Measure	Description	Time Frame
Number of Patients With or Without Overall Success at the PTE Visit in the CE Population	Comparison of overall success rates in the Clinical Evaluable (CE) population Overall success at PTE for the CE population was defined as all of the following criteria being met (Responder): Patient alive at Day 70 (± 5 days) post-randomization. No new metastatic foci or complications of the SAB infection. Resolution or improvement of SAB-related clinical signs and symptoms. Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female ≥ 18 years of age
Staphylococcus aureus bacteremia (SAB), based on at least one positive blood culture obtained within the 72 h prior to randomization
At least one of the following signs or symptoms of bacteremia:
1. fever (e.g.≥ 38 °C/100.4 °F measured orally)
2. white blood cell count > 10,000 or < 4,000 cells/µL, or > 10% immature neutrophils (bands)
3. tachycardia (heart rate > 90 bpm)
4. hypotension (systolic blood pressure < 90 mmHg)
At least one of the following:
1. SAB in patients undergoing chronic intermittent hemodialysis or peritoneal dialysis
2. Persistent SAB
3. Definite native-valve right-sided infective endocarditis by Modified Duke's Criteria
4. Other forms of complicated SAB
5. Osteomyelitis (including vertebral, sternal, or long-bone osteomyelitis)
6. Epidural or cerebral abscess
Other inclusion criteria have been applied

Exclusion Criteria:

Treatment with potentially effective (anti-staphylococcal) systemic antibacterial treatment for more than 48 h within the 7 days prior to randomization; Exception: Documented failure of bloodstream clearance
Bloodstream or non-bloodstream concomitant infections with Gram-negative bacteria that are known to be non-susceptible to either ceftobiprole or aztreonam
Left-sided infective endocarditis
Prosthetic cardiac valves or valve support rings, cardiac pacemakers, automatic implantable cardioverter-defibrillator, or left-ventricular assist devices
Community- or hospital-acquired pneumonia
Opportunistic infections within 30 days prior to randomization, where the underlying cause of these infections is still active
Requirement for continuous renal-replacement therapy
Women who are pregnant or nursing
Other exclusion criteria have been applied

Name	Affiliation	Role
Marc Engelhardt, MD	Basilea Pharmaceutica	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
eStudy Site - Chula Vista - PPDS		Chula Vista	California	91911	United States
Triple O Medical Services Inc

PubMed Identifier	Type	Citation	Retractions
31918579	Background	Hamed K, Engelhardt M, Jones ME, Saulay M, Holland TL, Seifert H, Fowler VG Jr. Ceftobiprole versus daptomycin in Staphylococcus aureus bacteremia: a novel protocol for a double-blind, Phase III trial. Future Microbiol. 2020 Jan;15(1):35-48. doi: 10.2217/fmb-2019-0332. Epub 2020 Jan 10.
37754204	Result	Holland TL, Cosgrove SE, Doernberg SB, Jenkins TC, Turner NA, Boucher HW, Pavlov O, Titov I, Kosulnykov S, Atanasov B, Poromanski I, Makhviladze M, Anderzhanova A, Stryjewski ME, Assadi Gehr M, Engelhardt M, Hamed K, Ionescu D, Jones M, Saulay M, Smart J, Seifert H, Fowler VG Jr; ERADICATE Study Group. Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia. N Engl J Med. 2023 Oct 12;389(15):1390-1401. doi: 10.1056/NEJMoa2300220. Epub 2023 Sep 27.

ID	Title	Description
FG000	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion
FG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 27, 2020	Feb 17, 2023

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

Number of Patients With or Without Overall Success at the Post-treatment Evaluation (PTE) Visit

Comparison of overall success rates in the mITT population

Overall success at PTE for the mITT population was defined as all of the following criteria being met (Responder):

Patient alive at Day 70 (± 5 days) post-randomization.
No new metastatic foci or complications of the SAB infection.
Resolution or improvement of SAB-related clinical signs and symptoms.
Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus)

The mITT population comprised the subset of patients in the ITT population who received any dose of study medication, and had a blood culture positive for S. aureus at baseline

Posted

Count of Participants

Participants

PTE visit on Day 70 (± 5 days) post-randomization

ID	Title	Description
OG000	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion
OG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam

Units	Counts
Participants	OG000189 OG001198

Title

Denominators

Categories

Number of responders

Title	Measurements
	OG000132 OG001136

Number of non-responders

Title	Measurements
	OG000

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	The observed difference in percentage of responders at PTE (ceftobiprole group minus the daptomycin group) were determined and a two-sided 95% confidence interval (CI) for the observed difference was computed, with adjustment for actual stratum (dialysis status and prior antibacterial treatment use). Cochran-Mantel-Haenszel (CMH) weights were used for the stratum weight in the calculation of the CI					Adjusted proportion difference	2.0			2-Sided	95	-7.1	11.1					Non-Inferiority	The non-inferiority hypothesis test was a one-sided hypothesis test performed at the 2.5% level of significance. If the lower limit of the two sided 95% CI for the difference in response rates in the mITT population was greater than -15%, the non-inferiority of ceftobiprole to daptomycin therapy was to be concluded.

Secondary

Number of Patients With or Without Overall Success at the PTE Visit in the CE Population

Comparison of overall success rates in the Clinical Evaluable (CE) population

Overall success at PTE for the CE population was defined as all of the following criteria being met (Responder):

Patient alive at Day 70 (± 5 days) post-randomization.
No new metastatic foci or complications of the SAB infection.
Resolution or improvement of SAB-related clinical signs and symptoms.
Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus)

The CE population comprised the subset of patients in the mITT population who complied with important pre-specified aspects of the study

Posted

Count of Participants

Participants

At PTE visit on Day 70 (± 5 days) post-randomization

ID	Title	Description
OG000	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion
OG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam

Units	Counts

Secondary

Number of Patients With Microbiological Eradication at the PTE Visit

Comparison of microbiological eradication rates in the mITT population. Microbiological eradication rate was defined as a negative blood culture for S. aureus during study treatment and another negative blood culture during the follow up period up to PTE.

The mITT population comprised the subset of patients in the ITT population who received any dose of study medication, and had a blood culture positive for S. aureus at baseline

Posted

Count of Participants

Participants

At PTE visit on Day 70 (± 5 days) post-randomization

ID	Title	Description
OG000	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion
OG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam

Units	Counts
Participants

Secondary

All-cause Mortality at the PTE Visit

Comparison of all-cause mortality rates in the mITT population

The mITT population comprised the subset of patients in the ITT population who received any dose of study medication, and had a blood culture positive for S. aureus at baseline

Posted

Count of Participants

Participants

At PTE visit on Day 70 (± 5 days) post-randomization

ID	Title	Description
OG000	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion
OG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam

Units	Counts
Participants	OG000

Secondary

Number of Patients With or Without New Metastatic Foci or Other Complications of SAB Developed After Day 7

Comparison of complication rates in the mITT population defined by number of patients with development of new metastatic foci or other complications of SAB after Day 7

The mITT population comprised the subset of patients in the ITT population who received any dose of study medication, and had a blood culture positive for S. aureus at baseline

Posted

Count of Participants

Participants

Assessment after Day 7 post-randomization through to post-treatment evaluation (PTE) visit on Day 70 (± 5 days)

ID	Title	Description
OG000	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion
OG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam

Units	Counts
Participants

Secondary

Time to Staphylococcus Aureus Bloodstream Clearance

Time-to-event in the mITT Bloodstream clearance was defined as two consecutive study days with blood-culture-negative assessments for S. aureus, without any subsequent S. aureus relapse or reinfection

The mITT population comprised the subset of patients in the ITT population who received any dose of study medication, and had a blood culture positive for S. aureus at baseline

Posted

Median

95% Confidence Interval

Days

Up to 6 weeks post-randomization

ID	Title	Description
OG000	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion
OG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam

Units	Counts
Participants	OG000

Secondary

Number of Patients With or Without Adverse Events (AEs)

Treatment-emergent adverse events in the safety population

The Safety population comprised all randomized patients who received any dose of study drug. Patients in the Safety population were analyzed according to the first study drug received.

Posted

Count of Participants

Participants

AEs were assessed from the first dose of study drug through the post-treatment evaluation (PTE) visit on Day 70 (± 5 days)

ID	Title	Description
OG000	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion
OG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Wound healing normal	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Angina unstable	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Arrhythmia	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Atrial thrombosis	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Cardiac arrest	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Cardiac failure	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0013 affected198 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Intracardiac mass	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Myocardial infarction	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Hypocoagulable state	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Generalised tonic-clonic seizure	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Hypoglycaemic seizure	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Presyncope	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Seizure	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Status epilepticus	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 affected191 at risk EG0010 affected198 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 affected191 at risk EG0010 affected198 at risk
Eosinophilic pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Eosinophilic pneumonia acute	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 affected191 at risk EG0012 affected198 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0012 affected198 at risk
Intra-abdominal haemorrhage	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Pancreatic haemorrhage	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Pancreatitis necrotising	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0012 affected198 at risk
Retroperitoneal haematoma	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Haematuria	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Renal haematoma	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Renal impairment	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Cutaneous vasculitis	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Pemphigoid	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Myopathy	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Abdominal abscess	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Abscess limb	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Bacteraemia	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Bacterial sepsis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0002 affected191 at risk EG0013 affected198 at risk
Candida sepsis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Endocarditis staphylococcal	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Gangrene	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Haematoma infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Intervertebral discitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0012 affected198 at risk
Laryngitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Lung abscess	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Mediastinitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Muscle abscess	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Osteomyelitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Pneumonia	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0003 affected191 at risk EG0012 affected198 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Psoas abscess	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Purulent pericarditis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Sepsis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Septic necrosis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Septic shock	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0004 affected191 at risk EG0018 affected198 at risk
Skin bacterial infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0013 affected198 at risk
Superinfection bacterial	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Urosepsis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Arteriovenous fistula thrombosis	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Haemodialysis complication	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Kidney rupture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Chloroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Leg amputation	Surgical and medical procedures	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Extremity necrosis	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Shock haemorrhagic	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0011 affected198 at risk
Death	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 24.0	Systematic Assessment	EG0004 affected191 at risk EG0012 affected198 at risk
Pyrexia	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected191 at risk EG0011 affected198 at risk
Cholestasis	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected191 at risk EG0010 affected198 at risk

ID	Term
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections
D018746	Systemic Inflammatory Response Syndrome
D007249	Inflammation
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D010456	Peptides, Cyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D055666	Lipopeptides
D008055	Lipids
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description
BG000	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion
BG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam
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	Ceftobiprole	Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) Ceftobiprole: Ceftobiprole 500 mg as a 2 h infusion	17	191	36	191	61	191
EG001	Daptomycin	Daptomycin 6 mg/kg, with or without aztreonam Daptomycin: Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam	18	198	45	198	45	198

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Blood potassium decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG00017 affected191 at risk EG0015 affected198 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG00012 affected191 at risk EG00115 affected198 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG00020 affected191 at risk EG00124 affected198 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00013 affected191 at risk EG0015 affected198 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00020 affected191 at risk EG0018 affected198 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG00016 affected191 at risk EG0014 affected198 at risk

ID	Term
D013203	Staphylococcal Infections
D016470	Bacteremia
D018805	Sepsis