Bacteriological efficacy of nafcillin and vancomycin alone or combined with rifampicin or amikacin in experimental meningitis due to methicillin-susceptible or -resistant Staphylococcus aureus.

Abstract

The pharmacokinetics and bacteriological efficacy of nafcillin (NFPC), vancomycin (VCM), amikacin (AMK) and rifampicin (RFP) alone and in VCM combinations were evaluated in the experimental rabbit meningitis caused by methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant Staphylococcus aureus (MRSA). The mean concentrations of NFPC, VCM, AMK and RFP in cerebrospinal fluid (CSF) with MSSA meningitis exceeded the minimal bactericidal concentrations of MSSA during 8 hours therapy period. The mean CSF penetration rates of the 4 drugs during therapy were from 1% to 26% which are comparable to those observed in humans with meningitis. The median CSF bactericidal titers of RFP, VCM plus RFP, AMK, VCM plus AMK regimens were larger than 1:8 during therapy of MSSA meningitis study. In experimental MRSA meningitis, RFP and VCM plus RFP achieved titers greater than 1: 16 during therapy and at 24 hours. No statistically significant reduction in the CSF bacterial colony count was obtained with any of the antibiotic regimens in MSSA meningitis. By contrast, in 8 hours MRSA meningitis model, significant reductions in the number of MRSA were observed in animals treated for 8 hours with VCM plus RFP (P less than 0.01), RFP (P less than 0.05), and NFPC plus RFP (P less than 0.01).