Diffusion of ceftriaxone (Ro 13-9004/001) in the cerebrospinal fluid. Comparison with other beta-lactam antibiotics in dogs with healthy meninges and in dogs with experimental meningitis.
After i.v injection of 50 and 100 mg/kg ceftriaxone in 1 h in dogs with healthy meninges, the cerebrospinal fluid (CSF) concentrations found between minutes 90 and 240 were an average of 0.37 (0.32-0.41) and 1.22 microgram/ml (1.02-1.56), respectively. In dogs with meningitis a dosage of 50 mg/kg yielded high concentrations from minutes 60 to 240: on average, 13.0 microgram/ml (9.9-14.9); 9.9 microgram/ml in the fourth hour. The concentrations obtained in dogs with healthy meninges were 10-100 times higher than the MICs for meningococci and Haemophilus influenzae. In the infected dogs, the concentrations obtained were enough to eliminate virtually all the bacteria responsible for meningitis (except Mycobacterium tuberculosis). In the dogs with healthy meninges, the ratio of the CSF/plasma AUCs was 0.61% after 50 mg/kg, and 1.00% after 100 mg/kg. In the infected dogs, this ratio was 22.4% after 50 mg/kg. Comparison of the ratio of AUCs obtained under ceftriaxone with that under other beta-lactam antibiotics shows the former to be one of the highest.