Pharmacokinetics and bacteriological efficacy of ticarcillin-clavulanic acid (timentin) in experimental Escherichia coli K-1 and Haemophilus influenzae type b meningitis

The pharmacokinetics and bacteriological efficacy of ticarcillin and clavulanic acid administered individually or in combination were assessed in rabbits with experimental Escherichia coli K-1 and Haemophilus influenzae type b meningitis. The mean penetrations into the cerebrospinal fluid (CSF) of infected animals after a single dose of ticarcillin-clavulanic acid were approximately 11 and 28% for ticarcillin and clavulanic acid, respectively. In continuous-infusion experiments, the mean penetrations into CSF were 14.6 and 35% for ticarcillin and clavulanic acid, respectively, in rabbits with E. coli meningitis and 6.1 and 24%, respectively, in rabbits with H. influenzae meningitis. In animals that received a continuous infusion of the two drugs alone or in combination, the median CSF bactericidal titers for E. coli were less than 1:2, less than 1:2, and 1:2 for ticarcillin, clavulanic acid, and ticarcillin-clavulanic acid, respectively, and for H. influenzae the titers were less than 1:2, less than 1:2, and 1:4, respectively. The addition of clavulanic acid potentiated significantly the bacteriological efficacy of ticarcillin in reducing the number of bacteria in CSF of infected rabbits. Additional studies in animals and humans are required before recommendations can be made regarding the use of ticarcillin-clavulanic acid for treatment of meningitis.