Ceftaroline + Rifampin Versus Vancomycin + Rifampin in the Treatment of Methicillin-ResistantMeningitis in an Experimental Rabbit Model.

Abstract

To compare the effectiveness ceftaroline-rifampicin (CR) and vancomycin-rifampicin (VR), against methicillin-resistant(MRSA) in a rabbit meningitis model, to compare the effects on brain tissues in terms of inflammation and apoptosis and to test the antibiotics via in vitro time-kill and synergy tests.Meningitis was induced using MRSA strain ATCC 43300. After 28 hours, the rabbits were split into three groups: control, VR, and CR. A CSF culture was taken at the start () and end of treatment (EOT)-the 24th hour of treatment. At EOT, the animals' brain tissues were examined for inflammation and apoptosis. The study strain was tested for a 24-hour time kill assay.At the EOT, statistically significant differences were observed between the treatment groups in terms of reducing the cerebrospinal fluid (CSF) bacterial count, achieving partial or complete treatment response, and exhibiting lower levels of neuronal apoptosis compared with the control group. However, there was no significant difference in all three parameters and in survival between the two treatment groups. The CR group exhibited a noticeable decrease in inflammation than the control group, but no significant difference was found between the control group versus VR and VR versus CR group. Rifampicin did not improve antibacterial efficacy in the in vitro time-kill assay.The CR arm showed better complete response and inflammation, but both treatments were similar in other parameters. CR combination was found as effective as VR combination for treating MRSA meningitis.