Abstract
The potential of ciprofloxacin for the therapy of Pseudomonas aeruginosa meningitis was evaluated in an animal model by determining the penetration of the drug into CSF, its concentration-dependent killing characteristics in vivo, and its relative efficacy compared with ceftazidime and tobramycin. Meningitis was produced in 40 rabbits by intracisternal injection of 3 × 107 organisms. The drugs were administered intravenously over seven hours, and simultaneous serum and CSF samples were taken at 0, 1, 3, 5, and 7h for determination of drug concentration and CSF bacterial counts. The percentage penetration of ciprofloxacin (18·4±12·3; mean±standard deviation) in infected rabbits was substantially increased over that found in uninfected rabbits (4·1±1·3). The rate of bacterial killing for animals treated with ceftazidime (100mg/kg/h) and high doses of tobramycin (2·5 mg/kg/h) was -0·51±0·13 (log10 cfu/ml/h). This was similar to the rate of killing (-0·48±0·2) found when ciprofloxacin was infused at 5 mg/kg/h, a dose that produced a mean serum level of 6·7±4·6 mg/l, which corresponds to concentrations achievable in humans. As dosages were increased (15 and 30 mg/kg/h), the rate of bacterial killing also increased (-0·70±0·1 and -0·89±0·4 respectively; r= 0·7407; P<0·0l). The drug shows promise in the treatment of Pseudomonas meningitis.