Bactericidal effect of ofloxacin alone and combined with fosfomycin or vancomycin against Staphylococcus aureus in vitro and in sera from volunteers.

The bactericidal activity of ofloxacin alone and in combination was evaluated against strains of Staphylococcus aureus by measuring MBCs, FBC indexes and by the killing curve technique. Bactericidal titres were determined in sera from volunteers given ofloxacin alone or in combination with fosfomycin or vancomycin. FBC indices less than 0.75 were observed with fosfomycin, showing moderate synergy. FBC indices of 1 were seen with vancomycin. Killing kinetic experiments indicated that ofloxacin (1 and 4 mg/l) exerted a rapid bactericidal effect (99.9% killing in 4 h); the combination of ofloxacin and fosfomycin was synergistic for one of three strains, while killing kinetics of ofloxacin were unaltered by fosfomycin for two of three strains or by vancomycin for the three strains. Sera collected two hours after ofloxacin or fosfomycin had been administered had bactericidal titres less than 1/2. Bactericidal titres were significantly greater in sera from volunteers given the combination of these two drugs. Similar bactericidal titres were obtained in sera after the administration of vancomycin alone or in combination with ofloxacin. A loading dose of 400 mg ofloxacin with subsequent doses of 200 mg had no significantly prolonged effect on bactericidal titres.