Antimicrobial activity of cefepime and rifampicin in cerebrospinal fluid in vitro

Though used for infections of the central nervous system, the pharmacodynamics of antimicrobial agents is commonly evaluated only in commercially available bacterial growth media. In the present study, the effects of cerebrospinal fluid (CSF) on bacterial killing by cefepime and rifampicin were investigated.

CSF was collected from patients who did not receive antibiotics. Time-kill curves were performed over 24 h using drug concentrations of 0.25-, 0.5-, 1-, 2-, 4- and 8-fold the respective MIC for the Staphylococcus aureus test strain. Killing curves were performed in Mueller-Hinton broth (MHB), in CSF incubated in ambient air (CSF(AIR)) and in CSF in air with 5% CO(2) (CSF(CO(2))). CO(2) served to adjust the pH of CSF to physiological values.

Sustained bacterial killing was achieved by cefepime at lower drug concentrations in CSF(CO(2)) than in MHB. In contrast, rifampicin concentrations above the MIC were required to exert sustained killing in CSF(CO(2)). Both drugs were least effective in CSF(AIR).

Standard susceptibility tests may lead to over- or underestimation of the activity of distinct antibiotics in CSF. Evaluation of the antimicrobial activity in pH-adjusted CSF can provide useful information on drugs considered for the treatment of bacterial infections residing in CSF.