Journal of Antimicrobial Chemotherapy (2000) 46, 385-390
© 2000 The British Society for Antimicrobial Chemotherapy
The effect of azithromycin on intracellular Legionella pneumophila in the Mono Mac 6 cell line at serum concentrations attainable in vivo
National Reference Centre of Hygiene and Institute of Environmental Medicine and Hospital Epidemiology, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany
We investigated the antimicrobial efficacy of clinically meaningful, low concentrations of azithromycin against intracellular growth of two clinical isolates of Legionella pneumophila. The mature monocytic cell line Mono Mac 6 was used as a model to investigate the effects of antimicrobial agents on L. pneumophila. Extracellular susceptibility was determined by microdilution susceptibility testing in BYE
broth after 48 h of incubation. Mono Mac 6 cells infected with L. pneumophila were incubated with various concentrations of azithromycin. After 2 days of incubation, intracellular bacteria were released from the phagocytes and plated on to BCYE agar. Addition of the intracellular-acting antibiotics azithromycin or ciprofloxacin at their MICs (0.5 and 0.015 mg/L, respectively) resulted in a significant decrease in cfu, of up to approximately 1 log10 after 48 h of incubation. In contrast, incubation of intraphagocytic L. pneumophila in the presence of antibiotics without intracellular activity (ceftizoxime, imipenem or amoxycillin–clavulanic acid) did not have any effect. Azithromycin inhibited intracellular replication at concentrations as low as 0.125 mg/L, approximately one-quarter of the extracellular MIC. The Mono Mac 6 cell line is a useful infection model for investigating the intracellular activity of antimicrobial agents in vitro. In accordance with clinical data and animal experiments, azithromycin and ciprofloxacin inhibited the intraphagocytic replication of L. pneumophila. In particular, azithromycin killed ingested legionellae in vitro at concentrations below the peak serum concentrations and below the MIC.
* Corresponding author. Tel: +49-761-270-5445; Fax: +49-761-270-5485; E-mail: djonas{at}iuk3.ukl.uni-freiburg.de
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