Structures of existing and new quinolones and relationship to bactericidal activity against Streptococcus pneumoniae.

The in-vitro bactericidal profiles of a number of quinolones against Streptococcus pneumoniae were investigated. Tosufloxacin was found to be the most bactericidal quinolone at the optimum bactericidal:MIC ratio (OBMR), followed by levofloxacin, ciprofloxacin and sparfloxacin, in order of potency. After exposure at the OBMR of each quinolone for 2 h, tosufloxacin showed a post-antibiotic effect (PAE) about 2.3-2.6 times longer than the other quinolones. Compounds with a 2,4-difluorophenyl group at the N-1 position in the quinolone nucleus had the greatest bactericidal activity and PAE. This activity exceeded that found with substitution of the quinolone nucleus at the C-7 position. Although the bactericidal activities of the quinolones correlated well with their PAEs, they were not always consistent with their MICs. These results suggest that bactericidal activity and PAE are governed by factors other than those which determine the MIC values, and a 2,4-difluorophenyl group at the N-1 position in the quinolone nucleus may play an important role in the expression of bactericidal activity and PAE against S. pneumoniae.