Id Journal Club

Ceftobiprole for
Treatment of
Complicated
Staphylococcus aureus
Bacteremia
ERADICATE Study
Kenedie Krout
PGY1 Pharmacy Resident
Franciscan Health Indianapolis

Objectives
• Provide an overview of ceftobiprole and its current
place in therapy
• Give a brief background and rationale for this study
• Present the analysis of the journal article
• Assess the outcomes of the study
• Evaluate how this study impacts today's practice
Background: Ceftobiprole
(Zevtera )
Ceftobiprole is a fifth-generation cephalosporin
MOA: prodrug converted in vivo to active drug with bactericidal activity by

binding to penicillin-binding proteins (PBPs)
Not currently approved in the United States
Used in the treatment of PNA due to Staphylococcus aureus, Streptococcus

pneumoniae, Escherichia coli, Klebsiella pneumoniae, and Haemophilus
influenzae
Used in the treatment of bloodstream infections caused by Staphylococcus

aureus
Ceftobiprole. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed December 2023.
Background and Rationale
Staphylococcus aureus bacteremia is a leading cause

of bloodstream infections
Current treatment options for MRSA include

vancomycin and daptomycin ± ceftaroline
Growing importance for rapidly bactericidal agents

against MRSA and MSSA
• Daptomycin and ceftobiprole are rapidly bactericidal while
vancomycin shows slower bactericidal effect
Fowler, V, MD, et al. clinical approach to Staphylococcus aureus bacteremia in adults. In: UpToDate, Wolters Kluwer. (Accessed on December 12, 2023.)
Ceftobiprole for Treatment of
Complicated Staphylococcus
aureus Bacteremia
ERADICATE Study
N Engl J Med. 2023;389:1390-401. DOI: 10.1056/NEKMoa2300220

Study Design
Adult patients
Phase 3,
hospitalized with
multinational, double-
Staphylococcus
blind, double-dummy,
aureus bacteremia,
randomized,
including infective
noninferiority trial
endocarditis
Study Drug Regimen
Randomized 1:1 to receive:
 Ceftobiprole
 500 mg IV every 6 hours during the first 8 days
and every 8 hours thereafter
OR
 Daptomycin
 Normal renal function (CrCl>30mL/min): 6-10
mg/kg every 24 hours
 Renal Impairment CrCl<30mL/min): 6-10
mg/kg every 48 hours
 Intermittent hemodialysis or peritoneal
dialysis: 6-10 mg/kg every 48 hours
Inclusion and Exclusion Criteria
Inclusion Criteria Exclusion Criteria
• ≥ 18 years of age • Treatment with potentially

• Signed informed consent effective systemic antibiotic
• At least one positive blood culture therapy
within 72 hours prior to • Bloodstream infection known to be
randomization non-susceptible to the study drugs
• At least two of the following: • Prosthetic cardiac devices/valves
• Fever ≥ 38°C/100.4°F • Clinically-relevant hypersensitivity
• WBC > 10,000 to beta lactams or daptomycin
• Tachycardia (HR>90 bpm) • Pregnant or nursing women
• Hypotension (SBP<90 mmHg)
Study Outcomes
Primary Endpoint
• Overall treatment success at 70 days post randomization
➢Survival, symptom improvement, S. aureus bloodstream
clearance, no use of other potentially effective antibiotics
Secondary Endpoints
• Death from any cause
• Microbiologic eradication
• Overall treatment success at day 70 in the per-protocol
population
• Time to S. aureus bloodstream clearance
Patient
Characteristics
Results
Results – Primary Outcome
Ceftobiprole Daptomycin Adjusted
(N=189) (N=198) Treatment
Difference (95% CI)
Overall treatment 132 (69.8%) 136 (68.7%) 2.0 (-7.1-11.1)
success at the post-
treatment evaluation
visit
• Reasons for treatment failure (ceftobiprole vs daptomycin)

• Discontinuation owing to lack of efficacy (4.8% vs 5.1%)
• New or worsening S. aureus complications (5.8% vs 5.6%)
• Use of non-trial antibiotics for S. aureus bacteremia (10.6% vs 9.6%)
• Death (9.0% vs 9.1%)
Results – Safety Outcomes
Results – Secondary Outcomes
Ceftobiprole Daptomycin Adjusted Treatment
(N=189) (N=198) Difference (95% CI)
Death through the post- 17 (9.0%) 18 (9.1%) -0.5 (-6.2-5.2)
treatment evaluation visit
Death due to S. aureus 7 (3.7%) 6 (3.0%) --
bacteremia
Microbiologic eradication 155 (82.0%) 153 (77.3%) 5.1 (-2.9-13.0)
at the post-treatment
evaluation visit
Development of new 11 (5.8%) 11 (5.6%) 0.1 (-4.6-4.8)
metastatic foci or other
complications of S. aureus
bacteremia after day 7
Median time to S. aureus 4 (3-5) 4 (3-5) --
bloodstream clearance
(days)
Subgroup Analysis
Subgroup Analysis
Strengths and Limitations of the Study
Strengths
• Large trial
• Double-blind design
• TEE occurred in 76% of patients
Limitations
• A quarter of patients had MRSA
• Over 80% of patients were in Eastern Europe
• Daptomycin was primarily dosed at 6 mg/kg/day
• Over 50% of patients were bacteremic due to SSTI
Conclusions and Applicability
Ceftobiprole was noninferior to daptomycin for the treatment

of S. aureus bacteremia.
This study shows that ceftobiprole may be a useful treatment

option for patients with complicated S. aureus bacteremia,
including right-sided infective endocarditis caused by MSSA or
MRSA.
Ceftobiprole for
Treatment of
Complicated
Staphylococcus aureus
Bacteremia
ERADICATE Study
Kenedie Krout
PGY1 Pharmacy Resident
Franciscan Health Indianapolis

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Ceftobiprole for

PGY1 Pharmacy Resident

Franciscan Health Indianapolis

MOA: prodrug converted in vivo to active drug with bactericidal activity by

Not currently approved in the United States

Used in the treatment of PNA due to Staphylococcus aureus, Streptococcus

Used in the treatment of bloodstream infections caused by Staphylococcus

Staphylococcus aureus bacteremia is a leading cause

Current treatment options for MRSA include

Growing importance for rapidly bactericidal agents

N Engl J Med. 2023;389:1390-401. DOI: 10.1056/NEKMoa2300220

• ≥ 18 years of age • Treatment with potentially

• Reasons for treatment failure (ceftobiprole vs daptomycin)

Ceftobiprole was noninferior to daptomycin for the treatment

This study shows that ceftobiprole may be a useful treatment

PGY1 Pharmacy Resident

Franciscan Health Indianapolis

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