Experimental study of cerebrospinal fluid tumor necrosis factor-alpha release in penicillin- and cephalosporin-resistant pneumococcal meningitis treated with different antibiotic schedules.

Abstract

To measure the inflammatory response in terms of tumor necrosis factor-alpha (TNF-α) levels in cerebrospinal fluid (CSF), using bacteriolytic versus nonbacteriolytic antibiotic therapy and adjunctive treatment with dexamethasone in an experimental rabbit model of pneumococcal meningitis. In a rabbit model of pneumococcal meningitis, we tested CSF TNF-α levels in several samples from rabbits infected with the HUB 2349 strain and treated with ceftriaxone 100mg/kg/d, ceftriaxone plus vancomycin 30mg/kg/d, or daptomycin at 15mg/kg or 25mg/kg. Daptomycin schedules were compared with the same doses in combination with dexamethasone at 0.125mg/kg every 12hours over a 26-hour period. The ceftriaxone group had the highest levels of TNF-α. TNF-α levels were significantly higher after ceftriaxone administration than in both daptomycin groups. The high-dose daptomycin group presented the lowest inflammatory levels in CSF samples. Adjunctive treatment with dexamethasone in this group modulated the inflammatory response, bringing down CSF TNF-α levels. CSF TNF-α levels were significantly lower in rabbits treated with daptomycin than in rabbits treated with ceftriaxone. Daptomycin avoided the inflammatory peak after administration observed in ceftriaxone-treated rabbits. The use of daptomycin plus dexamethasone achieved a significantly larger reduction in CSF TNF-α levels.