title: Experimental study of the efficacy of vancomycin, rifampicin and dexamethasone in the therapy of pneumococcal meningitis.
abstract: The object of the study was to assess the efficacy of rifampicin and the combination of rifampicin plus vancomycin in a rabbit model of experimental penicillin-resistant pneumococcal meningitis. We also studied the effect of concomitant dexamethasone on the CSF antibiotic levels and inflammatory parameters. The rabbit model of pneumococcal meningitis was used. Groups of eight rabbits were inoculated with 106 cfu/mL of a cephalosporin-resistant pneumococcal strain (MIC of cefotaxime/ceftriaxone 2 mg/L). Eighteen hours later they were treated with rifampicin 15 mg/kg/day, vancomycin 30 mg/kg/day or both plus minus dexamethasone (0.25 mg/kg/day) for 48 h. Serial CSF samples were withdrawn to carry out bacterial counts, antibiotic concentration and inflammatory parameters. Rifampicin and vancomycin promoted a reduction of >3 log cfu/mL at 6 and 24 h, and cfu were below the level of detection at 48 h. Combination therapy with vancomycin plus rifampicin was not synergic but it had similar efficacy to either antibiotic alone and it was able to reduce bacterial concentration below the level of detection at 48 h. Concomitant use of dexamethasone decreased vancomycin levels when it was used alone (P< 0.05), but not when it was used in combination with rifampicin. Rifampicin alone at 15 mg/kg/day produced a rapid bactericidal effect in this model of penicillin-resistant pneumococcal meningitis. The combination of vancomycin and rifampicin, although not synergic, proved to be equally effective. Using this combination in the clinical setting may allow rifampicin administration without emergence of resistance, and possibly concomitant dexamethasone administration without significant interference with CSF vancomycin levels.
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service and Microbiology Service, Ciutat Sanitària i Universitaria de Bellvitge, C.Feixa Larga s/n, 08907 L'Hospitalet, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Lacasa
authors.forename: C
authors.initials: C
authors.lastname: Cabellos
authors.forename: A
authors.initials: A
authors.lastname: Martos
authors.forename: A
authors.initials: A
authors.lastname: Fernández
authors.forename: F
authors.initials: F
authors.lastname: Tubau
authors.forename: P F
authors.initials: PF
authors.lastname: Viladrich
authors.forename: J
authors.initials: J
authors.lastname: Liñares
authors.forename: F
authors.initials: F
authors.lastname: Gudiol
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D002555:Cerebrospinal Fluid / Q000382:microbiology*; D015169:Colony Count, Microbial; D003907:Dexamethasone / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D008586:Meningitis, Pneumococcal / Q000150:complications / Q000188:drug therapy*; D010403:Penicillin Resistance; D011817:Rabbits; D012293:Rifampin / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D013296:Streptococcus pneumoniae / Q000302:isolation & purification; D013997:Time Factors; D014640:Vancomycin / Q000134:cerebrospinal fluid / Q000627:therapeutic use*
chemical_list: D014640:Vancomycin; D003907:Dexamethasone; D012293:Rifampin