title: Experimental study of the efficacy of linezolid alone and in combinations against experimental meningitis due to Staphylococcus aureus strains with decreased susceptibility to beta-lactams and glycopeptides.
abstract: BACKGROUND
  To evaluate in vitro and in vivo efficacies of linezolid, vancomycin, and the combination of linezolid and rifampicin against two Staphylococcus aureus strains with reduced susceptibility to beta-lactams and one of them also to glycopeptides.
  
  
  METHODS
  In vitro killing curves and a rabbit model: Meningitis was induced by intracisternal inoculation of 10(8) CFU/ml of each strain. Five hours later (0 h), rabbits were randomly assigned to control or to therapeutic groups. CSF bacterial counts, lactate and protein concentrations, and pharmacokinetic parameters were determined.
  
  
  RESULTS
  In vivo: linezolid and its combination with rifampicin reduced bacterial concentrations at 24 h, median cfu/mL 4.85 vs 3.87 (p < 0.05) for linezolid and 5.02 vs 4.21 (p < 0.05) for linezolid + rifampicin, against the glycopeptide intermediate S. aureus (GISA) strain and improved inflammatory parameters.
  
  
  CONCLUSIONS
  Despite the need for more experimental data, our results suggest that linezolid and its combinations could be considered as a potential alternative in difficult-to-treat CNS infections and especially in those due to GISA strains and deserve more studies.
authors: Laboratory of Experimental Infection, IDIBELL-Hospital Universitari de Bellvitge, Spain. Electronic address: ccabellos@bellvitgehospital.cat.
authors: Carmen
authors: C
authors: Cabellos
authors: Laboratory of Experimental Infection, IDIBELL-Hospital Universitari de Bellvitge, Spain.
authors: Carmen
authors: C
authors: Garrigós
authors: Laboratory of Experimental Infection, IDIBELL-Hospital Universitari de Bellvitge, Spain.
authors: Ferran
authors: F
authors: Taberner
authors: Laboratory of Experimental Infection, IDIBELL-Hospital Universitari de Bellvitge, Spain.
authors: Enriqueta
authors: E
authors: Force
authors: Laboratory of Experimental Infection, IDIBELL-Hospital Universitari de Bellvitge, Spain.
authors: M Eugenia
authors: ME
authors: Pachón-Ibañez
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology*; D000069349:Linezolid; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000494:pharmacology*; D011817:Rabbits; D011897:Random Allocation; D012293:Rifampin / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D023303:Oxazolidinones; D047090:beta-Lactams; D014640:Vancomycin; D000069349:Linezolid; D012293:Rifampin
keywords: GISA–MRSA; Linezolid; Meningitis; Staphylococcus aureus