Journal Article

Pharmacodynamic studies of moxifloxacin and erythromycin against intracellular <i>Legionella pneumophila</i> in an <i>in vitro</i> kinetic model

E. Tano, O. Cars and E. Löwdin

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 1, pages 240-242
Published in print July 2005 | ISSN: 0305-7453
Published online May 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki159
Pharmacodynamic studies of moxifloxacin and erythromycin against intracellular Legionella pneumophila in an in vitro kinetic model

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Background: Newer quinolones are highly active against Legionella pneumophila. Since this pathogen is intracellular, standard in vitro susceptibility tests may not accurately predict clinical efficacy. Few models for studies of intracellular Legionella have been described. In this study, we determined the pharmacodynamic activity of moxifloxacin against intracellular L. pneumophila in comparison with erythromycin.

Methods: A kinetic model for intracellular studies was constructed in which human pharmacokinetics could be simulated. The model consisted of a glass chamber with two exits and a metal rack fitting cell culture inserts. The inserts had a bottom membrane where cells could be cultured while nutrients and antibiotics passed through. The inserts were prepared with a monolayer of HEp-2 cells, which were exposed to a culture of L. pneumophila. At regular intervals cells were harvested and lysed, viable intracellular bacteria counted and compared with untreated controls.

Results: The MICs were 0.0156 mg/L for moxifloxacin and 0.5 mg/L for erythromycin. The human pharmacokinetics were simulated in the model with a mean initial antibiotic concentration of 2.4 mg/L for moxifloxacin and 8.4 mg/L for erythromycin. The mean half-life was 9 h for moxifloxacin and 3.4 h for erythromycin. At 12 h, a 2 log10 reduction in bacterial counts was seen in cells treated with moxifloxacin and no regrowth was detected at 24 h. Cells treated with erythromycin showed no reduction in intracellular L. pneumophilia at 12 h or 24 h. In experiments using static concentrations of 9 mg/L of erythromycin, similar results were obtained.

Conclusions: In this model, moxifloxacin exerts a significantly better antibacterial effect against intracellular L. pneumophila compared with erythromycin.

Keywords: HEp-2 cells; quinolones; pharmacokinetics

Journal Article.  1806 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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