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.

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.