ONCE-DAILY GENTAMICIN THERAPY FOR EXPERIMENTAL ESCHERICHIA-COLI MENINGITIS

In vitro and in vivo studies have demonstrated that the bacteriologic efficacy of once-daily aminoglycoside therapy is equivalent to that ac hieved with conventional multiple daily dosing. The impact of once-dai ly dosing for meningitis has not been studied. Using the well-characte rized rabbit meningitis model, we compared two regimens of the same da ily dosage of gentamicin given either once or in three divided doses f or 24 or 72 h. The initial 1 h mean cerebrospinal fluid (CSF) gentamic in concentration for animals receiving a single dose (2.9 +/- 1.7 mu g /ml) was threefold higher than that for animals receiving multiple dos es. The rate of bacterial killing in the first 8 h of treatment was si gnificantly greater for the animals with higher concentrations in thei r CSF (-0.21 +/- 0.19 versus -0.03 +/- 0.22 log(10) CFU/ml/h), suggest ing concentration-dependent killing. By 24 h, the mean reduction in ba cterial titers was similar for the two regimens. In animals treated fo r 72 h, no differences in bactericidal activity were noted at 24, 48, or 72 h. Gentamicin at two different dosages aas administered intracis ternally to a separate set of animals to achieve considerably higher C SF gentamicin concentrations. In these animals, the rate of bacterial clearance in the first 8 h (-0.52 +/- 0.15 and -0.58 +/- 0.14 log(10) CFU/ml/h for the lower and higher dosages, respectively) was significa ntly greater than that in animals treated intravenously. In conclusion , there is evidence of concentration-dependent killing with gentamicin early in treatment for experimental E. coli meningitis, and once-dail y dosing therapy appears to be at least as effective as multiple-dose therapy in reducing bacterial counts in CSF.