In a phase 3 noninferiority trial, ceftobiprole was noninferior to daptomycin for treating adult patients with complicated Staphylococcus aureus bacteremia, including methicillin-resistant S. aureus (MRSA). “Ceftobiprole may be a useful treatment option for patients with complicated S. aureus bacteremia, including infective endocarditis on the right side of the heart, caused by either [methicillin-sensitive S. aureus] or MRSA,” ERADICATE investigators conclude.
Using a double-blind, double-dummy, noninferiority design, adults with complicated S. aureus bacteremia were randomized to ceftobiprole 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin 6–10 mg/kg intravenously every 24 hours plus optional aztreonam. The primary outcome was overall treatment success 70 days after randomization, with success defined as survival, bacteremia clearance, symptom improvement, no new S. aureus bacteremia–related complications, and no receipt of other potentially effective antibiotics.
“Of 390 patients who underwent randomization, 387 (189 in the ceftobiprole group and 198 in the daptomycin group) had confirmed S. aureus bacteremia and received ceftobiprole or daptomycin (modified intention-to-treat population),” the authors write. “A total of 132 of 189 patients (69.8%) in the ceftobiprole group and 136 of 198 patients (68.7%) in the daptomycin group had overall treatment success (adjusted difference, 2.0 percentage points; 95% confidence interval [CI], −7.1 to 11.1). Findings appeared to be consistent between the ceftobiprole and daptomycin groups in key subgroups and with respect to secondary outcomes, including mortality (9.0% and 9.1%, respectively; 95% CI, −6.2 to 5.2) and the percentage of patients with microbiologic eradication (82.0% and 77.3%; 95% CI, −2.9 to 13.0). Adverse events were reported in 121 of 191 patients (63.4%) who received ceftobiprole and 117 of 198 patients (59.1%) who received daptomycin; serious adverse events were reported in 36 patients (18.8%) and 45 patients (22.7%), respectively. Gastrointestinal adverse events (primarily mild nausea) were more frequent with ceftobiprole.”