Ceftaroline Fosamil as a Potential Treatment for Central Nervous System Infections in Children

Abstract

Ceftaroline has been reported to show efficacy in limited adult clinical case studies including a report of a patient with a methicillin-resistant Staphylococcus aureus (MRSA) infection of a ventriculopleural shunt, and in 2 reports for use as a salvage therapy in a case of an epidural abscess infected with MRSA, as well as a case of methicillin-resistant Staphylococcus epidermidis (MRSE) ventriculostomy-related infection. The pharmacokinetic (PK) and pharmacodynamic (PD) properties of ceftaroline in healthy adults and neurosurgical patients have been assessed to develop population PK models used to perform simulations to evaluate the probability of target attainment of different ceftaroline dosing regimens for central nervous system (CNS) infections. Results from the simulations indicated that the penetration of ceftaroline into the cerebrospinal fluid was dependent on the degree of meningeal inflammation, suggesting that inflammation associated with infection would provide adequate antibiotic exposure, similar to other β-lactam antibiotics. Ceftaroline has a potential, unique role as a β-lactam antibiotic in the treatment of MRSA and coagulase negative staphylococci causing CNS infections as an alternative to vancomycin, the current standard of care. Support for treatment of CNS infections may be derived from further cerebrospinal fluid PK studies followed by PK/PD modeling prior to the conduct of prospective phase 2/3 clinical studies aimed at assessing the efficacy and safety of ceftaroline for the treatment of pediatric CNS infections. Ceftaroline's penetration enhanced by meningeal inflammation suggests that the drug could be a candidate to treat MRSA CNS infections.