Ceftobiprole as good as daptomycin in achieving S. aureus bloodstream clearance

“The bacterial properties of ceftobiprole translated into the clearance of the bloodstream by day 4, which was similar to daptomycin,” said the researchers.

Ceftobiprole, as the prodrug ceftobiprole medocaril, is an advanced-generation cephalosporin that exhibits bactericidal activity, similar to daptomycin, against methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) strains.

In this double-blind, phase III study, 390 patients with complicated S. aureus bacteremia who had a positive blood culture for S. aureus at baseline were randomized to receive either ceftobiprole 500 mg every 6 hours for the first 8 days and every 8 hours thereafter (n=192) or daptomycin 6–10 mg/kg every 24 hours (n=198), with optional aztreonam.

At a median of 4 days, S. aureus bloodstream clearance, defined as the occurrence of a negative blood culture for S. aureus on 2 consecutive study days, was achieved by 94.2 percent of patients treated with ceftobiprole and 92.9 percent of those treated with daptomycin. [ESCMID 2023, abstract 0774]

Based on a subgroup analysis of patients with MRSA or MSSA infections, both treatment groups demonstrated a consistent bloodstream clearance rate.

Among patients with MRSA infection, both ceftobiprole and daptomycin groups achieved S. aureus bloodstream clearance at a median of 3 days (94.3 percent and 95.2 percent, respectively).

Similarly, at a median of 5 days, S. aureus bloodstream clearance occurred in 93.3 percent of patients with MSSA infection in the ceftobiprole group and 87.8 percent in the daptomycin group.

After day 10, only three patients (all patients with MSSA) in the ceftobiprole group had an S. aureus-positive blood culture, whereas 10 patients (5 patients with MSSA and 5 patients with MSRA) were reported in the daptomycin group.

“Bacterial clearance is critical to clinical success for patients with S. aureus bacteremia as [previous] data demonstrated that continued blood culture positivity was associated with poor outcomes and an increased risk of death. In a particular study, each additional day of bacteremia was associated with a 16 percent increase in mortality,” wrote the researchers. [Clin Infect Dis 2020;70:566-573]

The US Food and Drug Administration recently approved ceftobiprole for the treatment of adults with S. aureus bacteremia. [https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibiotic-three-different-uses]