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Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Ceftobiprole medocaril sodium is the pro-drug of the active moiety ceftobiprole. Conversion from the prodrug ceftobiprole medocaril sodium, to the active moiety ceftobiprole, occurs rapidly and is mediated by non-specific plasma esterases. Ceftobiprole undergoes minimal metabolism to the open-ring metabolite, which is microbiologically inactive.
Ceftobiprole
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Andrew Henderson, Baek-Nam Kim, David L. Paterson
Ceftobiprole demonstrates antibacterial activity against Enterobacteriaceae and resembles that of cefepime more closely than that of ceftazidime (Jones, 2007). As with cefepime, ceftobiprole activity was decreased among isolates of Gram-negative bacilli producing ESBLs and other class A, B, and D cephalosporinases (Green et al., 2014; Hebeisen et al., 2001; Pillar et al., 2008; Queenan et al., 2007; Rouse et al., 2006).
Antimicrobial prescribing for treatment of serious infections caused by Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in pediatrics: an expert review
Published in Expert Review of Anti-infective Therapy, 2021
Sean N. Avedissian, Nathanial J. Rhodes, Christopher L. Shaffer, Lan Tran, John S. Bradley, Jennifer Le
Ceftobiprole is also a fifth-generation cephalosporin but is not yet available in the United States. It binds to PBP2-4 with high affinity for PBP 2a and PBP 3, conferring activity against both MRSA as well as Gram-negative pathogens [67,68]. Ceftobiprole was recently studied in a large, global, prospective trial in adult patients with HAP and VAP; overall, the statistical analysis for the FDA predetermined non-inferiority target was not met. Ceftobiprole appeared non-inferior for in the subgroup of patients with HAP but it failed to demonstrate non-inferiority vs ceftazidime and linezolid for patients with VAP [69]. Recently, a ‘real-world’ observational study described the clinical outcomes of patients treated with ceftobiprole [70]. The authors reported favorable outcomes in 68.9% of patients. A phase 3 comparative prospective study of ceftobiprole in children with community-acquired (vs ceftriaxone) and hospital-acquired (vs ceftazidime) pneumonia was recently completed from study sites in Eastern Europe, but no data have yet been published. This raises the possibility that ceftobiprole could be an alternative therapy, with activity similar to ceftaroline for S. aureus infections. A clinical trial comparing daptomycin to ceftobiprole for S. aureus bacteremia in adults, including right-sided endocarditis, is ongoing [71]. A phase 1 clinical trial to assess the PK of ceftobiprole in neonates and young infants using prolonged infusing (4 hours) to maximize time-dependent killing was closed due to difficulty in enrolling patients.
Ceftobiprole medocaril for the treatment of community-acquired pneumonia
Published in Expert Opinion on Pharmacotherapy, 2018
Vicenç Falcó, Joaquin Burgos, Benito Almirante
Protein-binding proteins (PBPs), the targets of β-lactam antibiotics, are membrane-associated enzymes involved in the last steps of peptidoglycan biosynthesis. Ceftobiprole binds to PBPs interfering with the cell wall synthesis and leading to bacterial death. Ceftobiprole is relatively stable toward AmpC β-lactamases and has a strong affinity for PBPs, including PBP 2A, which mediates resistance to β-lactams in MRSA and methicillin-resistant coagulase-negative staphylococci [31]. Precisely the affinity to bind PBP2a explains the activity of ceftobiprole against MRSA and distinguishes it from other cephalosporins [32]. Ceftobiprole exhibits also a high affinity to bind other PBPs such as PBP2x in penicillin-resistant S. pneumoniae, and PBP3 and other essential PBPs in methicillin-susceptible S. aureus (MSSA), Escherichia coli, and P. aeruginosa [33]. PBP2a is encoded by the mecA gen. It has been recently demonstrated that MRSA strains with some mecA mutations may confer resistance to ceftobiprole [34].
Ceftobiprole: drug evaluation and place in therapy
Published in Expert Review of Anti-infective Therapy, 2019
Daniele Roberto Giacobbe, Francesco Giuseppe De Rosa, Valerio Del Bono, Paolo Antonio Grossi, Federico Pea, Nicola Petrosillo, Gian Maria Rossolini, Carlo Tascini, Mario Tumbarello, Pierluigi Viale, Matteo Bassetti
Similar to other cephalosporins, ceftobiprole exhibits time-dependent antibacterial activity. It has been shown in experimental infection models that maintenance of plasma concentrations above the MIC for 30% to 60% of the dosing interval (t> MIC) may guarantee effective bactericidal activity, in terms of >2–3 log10 decrease in CFU over 24 h, against S. aureus, S. pneumoniae and wild-type Enterobacterales [27]. Noteworthy, the pharmacodynamic target of ceftobiprole against S. aureus in experimental pneumonia models was very similar (t> MIC of 40%) among phenotypically diverse strains (methicillin-susceptible S. aureus, community-associated (CA)-MRSA and healthcare-acquired (HA)-MRSA) [28].