Infections in the cerebrospinal fluid (CSF) occur in an area of impaired host defenses; therefore, bactericidal
antibiotics that reach adequate concentrations in the CSF are necessary for treatment. Measurements of
antibiotic penetration into the CSF include CSF inhibitory and bactericidal titers, the absolute
antibiotic concentration in the CSF, and the CSF: serum concentration ratio. We present the case of a patient with
Listeria monocytogenes meningitis who failed to respond clinically to standard
therapy, and whose organism demonstrated tolerance to
Ampicillin (MBC: MIC = 258:1) that successfully responded to
trimethoprim-sulfamethoxazole (
TMP-SMX). The CSF peak bactericidal titer to
TMP-SMX was 1:8, corresponding to that reported as necessary for successful outcome in patients with
meningitis. The CSF peak: MBC ratios for
TMP and SMX were less than 3:1 and equal to 3:1, respectively. These individual ratios are lower than those suggested for successful treatment of
meningitis; however, the recommended ratios were established using single agents and did not account for synergistic activity with a
drug combination such as
TMP-SMX. The failure of standard
therapy in this patient underscores the importance of MIC/MBC testing when tolerance is suspected or when CSF penetration of
antibiotics is relatively poor. In addition, measurements of CSF inhibitory and bactericidal titers, which incorporate the
antibiotic concentration in the CSF, susceptibility of the infecting microorganism, and host defense factors, may be useful in monitoring patients with
meningitis.