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Volume 50, Number 4, August 2017

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

M. Vivas, E. Force, C. El Haj, F. Tubau, J. Ariza, C. Cabellos


Corresponding author:

M. Vivas, Corresponding author. Laboratory of Experimental Infection, Infectious Diseases Department, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. 


Background and purpose: 

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 100 mg/kg/d, ceftriaxone plus vancomycin 30 mg/kg/d, or daptomycin at 15 mg/kg or 25 mg/kg. Daptomycin schedules were compared with the same doses in combination with dexamethasone at 0.125 mg/kg every 12 hours 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. 


Key words:

ceftriaxone, cytokines, daptomycin, dexamethasone, Streptococcus pneumoniae