Pharmacodynamic studies of moxifloxacin and erythromycin against intracellular Legionella pneumophila in an in vitro kinetic model.
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 log(10) 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.
Tano
E
E
Section of Clinical Bacteriology, Antibiotic Research Unit, Department of Medical Sciences, Uppsala University Hospital, Sweden.
Cars
O
O
Löwdin
E
E
D001372:Aza Compounds / Q000494:pharmacology*; D002460:Cell Line; D004917:Erythromycin / Q000494:pharmacology*; D024841:Fluoroquinolones; D006801:Humans; D007700:Kinetics; D016952:Legionella pneumophila / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D000077266:Moxifloxacin; D011804:Quinolines / Q000494:pharmacology*
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D004917:Erythromycin; D000077266:Moxifloxacin