Trimethoprim-sulfamethoxazole vs. ampicillin in the treatment of experimental meningitis due to Streptococcus pneumoniae.

When given in combination, both trimethoprim and sulfamethoxazole penetrated well into the cerebrospinal fluid of rabbits with experimental pneumococcal meningitis, reaching concentrations that should have been adequate for synergistic killing of Streptococcus pneumoniae. However, trimethoprim-sulfamethoxazole was less effective than ampicillin in the treatment of this experimental infection. The effect of the combination on pneumococci in vivo was bacteriostatic rather than bactericidal, possibly because the number of pneumococci in the cerebrospinal fluid of the rabbits at the start of treatment was larger than that in the inoculum used for in vitro sensitivity tests.