title: Intracellular activity of trovafloxacin against Staphylococcus aureus.
abstract: The effect of trovafloxacin on Staphylococcus aureus ingested by human granulocytes or monocytes was compared with that on S. aureus in cell-free medium. Maximum growth inhibition (E(R,max)) by the antibiotic was 0.530 log10/h for S. aureus within granulocytes, 0.912 log10/h for S. aureus within monocytes, and 1.830-1.916 log10/h for S. aureus in medium. EC50, the concentration at which 50% of the maximum growth inhibition is achieved, did not differ significantly under the conditions investigated. After inhibition of intracellular killing by granulocytes with sodium fluoride, the intracellular antibacterial activity of trovafloxacin was still less than that in medium. A 3.4 times higher concentration was needed to achieve the same effect on phagocytosed S. aureus as in cell-free medium. Trovafloxacin binds more strongly to granulocytes than to monocytes, the respective cellular concentrations being 10 and four times higher than that in medium. In conclusion, the activity of trovafloxacin against S. aureus ingested by human granulocytes or monocytes is less than that against S. aureus in cell-free medium and is not related to the cell-associated concentration. Intracellular conditions are not favourable for the antibacterial activity of trovafloxacin.
authors.affiliation: Leiden University Medical Centre, Department of Infectious Diseases, The Netherlands. P.J.van_den_Broek@thuisnet.leidenuniv.nl
authors.forename: P J
authors.initials: PJ
authors.lastname: van den Broek
authors.forename: T G
authors.initials: TG
authors.lastname: Koot
authors.forename: E
authors.initials: E
authors.lastname: van Strijen
authors.forename: H
authors.initials: H
authors.lastname: Mattie
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones; D006098:Granulocytes / Q000187:drug effects* / Q000382:microbiology; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000382:microbiology; D009287:Naphthyridines / Q000494:pharmacology*; D010587:Phagocytosis; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin