Ceftobiprole: drug evaluation and place in therapy

Abstract

Introduction: Ceftobiprole is a fifth-generation cephalosporin with a broad spectrum of antimicrobial activity, including also methicillin-resistant Staphylococcus aureus (MRSA). Ceftobiprole is approved for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia, in several European and non-European countries. Areas covered: In this narrative review, we discuss the current place in therapy of ceftobiprole, both within and outside approved indications. An inductive MEDLINE/PubMed search of the available literature was conducted. Expert opinion: There are three main reasons which render ceftobiprole an attractive option for the empirical and targeted treatment of CAP and HAP: (i) its broad spectrum of activity; (ii) its activity against MRSA; (iii) its good safety profile. For these indications, ceftobiprole should be employed thoughtfully, in those scenarios in which its intrinsic advantages could be maximized. The use of ceftobiprole outside approved indications could be justified in specific scenarios, such as when other approved alternatives are ineffective, when the risk of toxicity due to other agents is unacceptable, and for salvage therapy. In the near future, ongoing phase 3 studies and further observational experiences could both enlarge the current panel of approved indications and enrich our knowledge on the use of ceftobiprole for off-label indications. ARTICLE HISTORY

Ceftobiprole Perspective: Current and Potential Future Indications

“…In severe CAP leading to influenza-associated complications, ceftobiprole can be an excellent option to ensure that realistic coverage of community-acquired MRSA can be assured, especially in patients with diabetes, obesity, or chronic obstructive pulmonary disease (COPD), as well as patients over 65 years of age with pulmonary anomalies or with underlying malignancies [5,10,11].…”

“…Since it became available, particular interest has been focused on ceftobiprole beyond the approved indications and, in particular, on IE, probably because of (i) its broadspectrum activity, including Gram-positive and Gram-negative bacteria, especially both MSSA and MRSA; (ii) its bactericidal activity; and (iii) its high tolerability [5]. Animal models of IE treated with ceftobiprole have provided promising results despite being limited mostly to staphylococcal IE.…”

“…Ceftobiprole medocaril, a fifth-generation extended-spectrum cephalosporin, is endorsed in Europe at a standard dosage of 500 mg intravenously every 8 h for managing adult community-acquired pneumonia (CAP) [1], non-ventilator-associated hospitalacquired pneumonia (HAP) [2], and skin and soft-tissue infections (SSTIs) [3,4], including diabetic foot infections. Ceftobiprole was the first β-lactam antibiotic to show in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus (VRSA), and penicillin-resistant Streptococcus pneumoniae (PRSP) [5]. It exerts its antibacterial activity by inhibiting the transpeptidase moiety of penicillin-binding proteins (PBPs) [6].…”

“…It exerts its antibacterial activity by inhibiting the transpeptidase moiety of penicillin-binding proteins (PBPs) [6]. More precisely, ceftobiprole's in vitro activity demonstrates potent binding against PBPs of Gram-positive bacteria (GPB), including those with decreased β-lactam sensitivity, such as PBP2x and PBP2bin PRSP and, PBPa, which confers methicillin resistance to S. aureus strains [5,6]. In vitro bactericidal activity against MRSA strains showed kinetics either similar or superior to those of vancomycin and linezolid [7].…”

“…The drug is degraded by both extended-spectrum β-lactamases (ESBLs) and serine-carbapenemases. Class B, several class C chromosomal AmpC-type βlactamases, and some class D β-lactamases have lytic action on ceftobiprole's structure [5,6].…”