title: Experimental study of cerebrospinal fluid tumor necrosis factor-alpha release in penicillin- and cephalosporin-resistant pneumococcal meningitis treated with different antibiotic schedules.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: mireiavivas@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Vivas
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Force
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: El Haj
authors.affiliation: Microbiology Department, IDIBELL-Hospital Universitari de Bellvitge and CIBERES ISCIII, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Tubau
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ariza
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Cabellos
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002511:Cephalosporins / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology*; D010406:Penicillins / Q000494:pharmacology; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid*; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D002511:Cephalosporins; D010406:Penicillins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone
keywords: Streptococcus pneumoniae; ceftriaxone; cytokines; daptomycin; dexamethasone