The objective of the current study was to evaluate the bactericidal activity of levofloxacin against Streptococcus pneumoniae at concentrations equivalent to those present in serum after a po dosage of 500 mg. Nine S. pneumoniae strains (one penicillin G-resistant, one penicillin G-intermediate resistant, and two penicillin G- and cefotaxime-resistant) were exposed to a levofloxacin concentration of 6 mg/L diluted at a terminal half-life (t1/2) of 8 h. Surviving S. pneumoniae (cfu/mL) were quantified up to 24 h by the membrane filtration method. Levofloxacin was rapidly bactericidal and reduced the quantity of inoculum to below the detection level of 10 cfu/mL within 2.5-5.15 h, irrespective of susceptibility to penicillin G or cefotaxime. No viable S. pneumoniae could be detected at the end of the observation period (24 h). All strains except one (strain 17134) had an MIC < 1.0 mg/L, and the minimum bactericidal concentrations (MBCs) were, at the most, one dilution higher than the respective MICs. The inoculum was high, ranging from 2.9 x 10(5) to 7.5 x 10(6) cfu/mL. The time required to achieve 99% death ranged from 0.9 to 3.1 h, and was longest for strain 17134 which had an MIC of 1.0 mg/L and an MBC of 2.0 mg/L. A 99.9% reduction in inoculum was achieved within 1.5-4.15 h. At a serum concentration achievable after a single po dosage of 500 mg, levofloxacin showed rapid and complete bactericidal activity against the S. pneumoniae strains tested.