The Positioning of Ceftobiprole in the Treatment of <i>Staphylococcus aureus</i> Bacteremia

To The Editor—We appreciate the interest that Membrillo de Novales and colleagues have expressed regarding our article. Here, we address some of their concerns. Membrillo de Novales et al raised questions about the methodology used to support the recommendations in our recent article. For our invited clinical review, we were asked to present “personal, authoritative viewpoints” on elements of clinical practice, as opposed to writing a clinical practice guideline. Accordingly, we sought to summarize available evidence and discuss management practices informed by our clinical experience and practice settings. We do agree with Membrillo de Novales and colleagues that the positioning of ceftobiprole deserves additional consideration for the management of Staphylococcus aureus bacteremia (SAB). A fifth-generation cephalosporin that has activity against a wide range of gram-positive bacteria (including methicillin-resistant S. aureus [MRSA]) and gram-negative bacteria, ceftobiprole is an attractive agent for treatment of complex and potentially drug-resistant infections. Recently, there has been an increased use of ceftobiprole in countries where it is available, although definitive conclusions are challenging to draw from nonrandomized observational studies [1–4]. Results from the "Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia" (ERADICATE) trial, a randomized, phase 3, double-blind, noninferiority trial, were recently published and showed that ceftobiprole met the prespecified noninferiority margin (15%) for clinical success at 70 days compared with daptomycin ± aztreonam [5], although there were numerically worse outcomes with ceftobiprole for the subgroup of participants with MRSA (nonsignificant). Nonetheless, these results are certainly important and represent a major research milestone in the treatment of SAB, a condition for which new antimicrobial agents are direly needed. As Membrillo de Novales and colleagues point out, the results of the ERADICATE trial were published largely contemporaneously to our review, and we felt that it was important to include a discussion of this significant trial. That said, ceftobiprole does not yet have regulatory approval in the United States (where it is not even commercially available), Canada, or the European Union for the particular indication of SAB. This as well as the relatively limited (although increasing) clinical experience with ceftobiprole for salvage treatment of SAB led us to position it similarly to ceftaroline in our review, although we acknowledge that the results of the ERADICATE trial are notable and certainly constitute a stronger evidence base for ceftobiprole compared with ceftaroline for SAB. In summary, we appreciate Membrillo de Novales and colleagues’ comments on the role that ceftobiprole should occupy in the treatment of SAB. We look forward to greater availability and clinical experience with this agent in the years to come. Editor's note. The state-of-the-art reviews that appear in Clinical Infectious Diseases are not meant to represent clinical guidelines but rather personal authoritative viewpoints on elements of clinical practice.

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