Evaluation of Ceftobiprole Activity against a Variety of Gram-Negative Pathogens, Including Escherichia coli, Haemophilus influenzae (β-Lactamase Positive and β-Lactamase Negative), and Klebsiella pneumoniae, in a Rabbit Meningitis Model

Abstract

ABSTRACTCeftobiprole medocaril, a new cephalosporin, is highly active against a broad spectrum of Gram-positive and Gram-negative clinical pathogens, including methicillin-resistantStaphylococcus aureus(MRSA) and penicillin-resistant pneumococci. In this study, we tested ceftobiprole against various Gram-negative pathogens in a rabbit meningitis model and determined its penetration into the cerebrospinal fluid (CSF). In this animal model, ceftobiprole produced an antibacterial activity similar to that of cefepime against anEscherichia colistrain, aKlebsiella pneumoniaestrain, and a β-lactamase-negativeHaemophilus influenzaestrain. Against a β-lactamase-positiveH. influenzaestrain, ceftobiprole was significantly superior. The penetration of ceftobiprole through inflamed meninges reached about 16% of serum levels compared to about 2% of serum levels through uninflamed meninges.