Bactericidal activity of levofloxacin against Streptococcus pneumoniae in an in-vitro model simulating serum pharmacokinetic parameters.
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.
Klinikum der Johann Wolfgang Goethe-Universitaet, Zentrum der Inneren Medizin, Medizinische Klinik III, Frankfurt, Germany. shah@em.uni-frankfurt.de
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D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D015242:Ofloxacin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D010403:Penicillin Resistance; D015610:Serum Bactericidal Test; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification
D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin