Antibiotic Therapy, Endotoxin Concentration in Cerebrospinal Fluid, and Brain Edema in Experimental Escherichia coli Meningitis in Rabbits

We investigated the effect of cefotaxime and chloramphenicol on endotoxin concentrations in cerebrospinal fluid (CSF) and on the development of brain edema in rabbits with Escherichia coli meningitis. Both antibiotics were similarly effective in reducing bacterial titers. Cefotaxime, but not chloramphenicol, induced a marked increase of endotoxin in CSF, from log10 1.5 ± 0.8 to log10 2.8 ± 0.7 ng/ml (P < .01). This result was associated with an increase in brain water content (405 ± 12 g of water/100 g of dry weight compared with 389 ± 8 g in untreated controls; P < .01), whereas in animals treated with chloramphenicol, brain water content was identical to controls. The cefotaxime-induced increase in endotoxin concentration and brain edema were both neutralized by polymyxin B, which binds to the lipid A moiety of endotoxin, or by a monoclonal antibody to lipid A. These results indicate that treating gram-negative bacillary meningitis with selected antibiotics induces increased endotoxin concentrations in CSF that are associated with brain edem

Ciprofioxacin in experimental Pseudomonas aeruginosa meningitis in rabbits

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 x 10 7 organisms. The drugs were administered intravenously over seven hours, and simultaneous serum and CSF samples were taken at 0, 1, 3, 5, and 7 h for determination of drug concentration and CSF bacterial counts. The percentage penetration of ciprofloxacin (18-4± 12&apos;3; mean±standard deviation) in infected rabbits was substantially increased over that found in uninfected rabbits (4&apos;1 ± 1· 3). The rate of bacterial killing for animals treated with ceftazidime (100 mg/kg/h) and high doses of tobramycin (2·5 mg/kg/h) was -0·51 ±0·13 (lOglO 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/I, 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&apos;70 ±O&apos;I and -0·89±0·4 respectively; r = 0·7407; P&lt;O·OI). The drug shows promise in the treatment of pseudomonas meningitis