title: Bactericidal effects of amoxycillin/clavulanic acid against intracellular Legionella pneumophila in tissue culture studies.
abstract: The bactericidal effects of amoxycillin, clavulanic acid and amoxycillin plus clavulanic acid were determined against Legionella pneumophila growing intracellularly in MRC-5 human fetal lung fibroblast cells. The strain of L. pneumophila was shown to be growing within the cells by transmission electron microscopy and this was confirmed by the results of bactericidal tests in which gentamicin was shown to be ineffective in preventing growth of the organism in the tissue culture system. Amoxycillin failed to prevent infection of the cell monolayers and had no effect on the growth of intracellular L. pneumophila. Transmission electron microscopy showed the presence of large numbers of bacteria of normal morphology within the fibroblasts. In contrast, clavulanic acid and amoxycillin/clavulanic acid protected the cell sheets from the effects of infection with L. pneumophila and reduced the numbers of intracellular bacteria to the same extent as erythromycin. Also, bacteria of abnormal morphology were observed within fibroblast cells of the cultures treated with clavulanic acid and the combination. These data demonstrate the penetration of clavulanic acid, when used alone or in the presence of amoxycillin, into cells infected with L. pneumophila and the resulting bactericidal activity of the agents against intracellular bacteria.
authors.affiliation: Beecham Pharmaceuticals Research Division, Betchworth, Surrey, UK.
authors.forename: D H
authors.initials: DH
authors.lastname: Stokes
authors.forename: M J
authors.initials: MJ
authors.lastname: Wilkinson
authors.forename: J
authors.initials: J
authors.lastname: Tyler
authors.forename: B
authors.initials: B
authors.lastname: Slocombe
authors.forename: R
authors.initials: R
authors.lastname: Sutherland
mesh_terms: D000658:Amoxicillin / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002969:Clavulanic Acids / Q000378:metabolism / Q000494:pharmacology*; D046508:Culture Techniques; D006801:Humans; D007875:Legionella / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D013997:Time Factors
chemical_list: D002969:Clavulanic Acids; D000658:Amoxicillin