Safety and effectiveness of fifth generation cephalosporins for the treatment of methicillin-resistant staphylococcus aureus bloodstream infections: a narrative review exploring past, present, and future

ABSTRACT

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is a major issue in healthcare, since it is often associated with endocarditis or deep site foci. Relevant morbidity and mortality associated with MRSA-BSIs forced the development of new antibiotic strategies; in particular, this review will focus the attention on fifth-generation cephalosporins (ceftaroline/ceftobiprole), that are the only ß-lactams active against MRSA.

Areas covered

The review discusses the available randomized controlled trials and real-world observational studies conducted on safety and effectiveness of ceftaroline/ceftobiprole for the treatment of MRSA-BSIs. Finally, a proposal of MRSA-BSI treatment flowchart, based on fifth-generation cephalosporins, is described.

Expert opinion

The use of anti-MRSA cephalosporins is an acceptable choice either in monotherapy or combination therapy for the treatment of MRSA-BSIs due to their relevant effectiveness and safety. Particularly, their use may be advisable in combination therapy in case of severe infections (including endocarditis or persistent bacteriemia) or in monotherapy in subjects at higher risk of drugs-induced toxicity with older regimens. On the contrary, caution should be taken in case of suspected/ascertained central nervous system infections due to inconsistent data regarding penetration of these drugs in cerebrospinal fluid and brain tissues.

KEYWORDS:

• Fifth generation cephalosporins
• ceftaroline
• ceftobiprole
• staphylococcus aureus
• methicillin-resistance
• MRSA
• bloodstream infections

Article highlights

• Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of bloodstream infections, causing a significant burden of morbidity and mortality.

• The fifth generation cephalosporins (ceftaroline and ceftobiprole) represent the only ß-lactams active against MRSA.

• Ceftaroline and ceftobiprole showed a relevant effectiveness and safety in both randomized controlled trials and observational studies involving patients with MRSA bloodstream infections.

• Ceftaroline and ceftobiprole can be considered non-inferior to vancomycin or daptomycin for the treatment of MRSA bloodstream infections.

• Given their pharmacokinetics/pharmacodynamics characteristics, ceftaroline and ceftobiprole may represent the backbone of MRSA bloodstream infections in mono- or combination therapy.

• Despite many research questions are still open, including the best place in therapy of these drugs, the use ceftaroline and ceftobiprole should be considered a valuable treatment option for MRSA bloodstream infections.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

MB and DFB were involved in the conception and design of the work; DFB, AB, LB, VC, LD, and MG produced the first draft of the manuscript; MB, AS, PV, and FP revised the paper critically for intellectual content. All authors gave the final approval of the version to be published and agree to be accountable for all aspects of the work.

Additional information

Funding

This research was supported by EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT).