Ceftobiprole in the Treatment of Patients With Staphylococcus Aureus Bacteremia

Patients were randomized 1:1 to ceftobiprole or the comparator regimen. Randomization was stratified by study site, dialysis status, and prior antibacterial treatment use within 7 days before randomization.

The three phases of the study were:

• Screening assessments of up to 72 hours prior to randomization
• Randomization and subsequent active treatment with intravenous (i.v.) study drug (ceftobiprole or daptomycin ± aztreonam).
• Post-treatment, comprising an end of trial (EOT) visit (within 72 hours of last study-drug administration), Day 35 (± 3 days), Day 42 (± 3 days), and a post-treatment evaluation (PTE) visit on Day 70 (± 5 days) post-randomization.

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:

• fever (e.g.≥ 38 °C/100.4 °F measured orally)
• white blood cell count > 10,000 or < 4,000 cells/µL, or > 10% immature neutrophils (bands)
• tachycardia (heart rate > 90 bpm)
• hypotension (systolic blood pressure < 90 mmHg)
• At least one of the following:

• SAB in patients undergoing chronic intermittent hemodialysis or peritoneal dialysis
• Persistent SAB
• Definite native-valve right-sided infective endocarditis by Modified Duke's Criteria
• Other forms of complicated SAB
• Osteomyelitis (including vertebral, sternal, or long-bone osteomyelitis)
• 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