The effect of azithromycin on intracellular Legionella pneumophila in the Mono Mac 6 cell line at serum concentrations attainable in vivo

We investigated the antimicrobial efficacy of clinically meaningful, low co ncentrations of azithromycin against intracellular growth of two clinical i solates 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 microdiluti on susceptibility testing in BYE alpha. broth after 48 h of incubation. Mon o Mac 6 cells infected with L.. pneumophila were incubated with various con centrations of azithromycin. After 2 days of incubation, intracellular bact eria were released from the phagocytes and plated on to BCYE alpha agar. Ad dition of the intracellular-acting antibiotics azithromycin or ciprofloxaci n at their MICs (0.5 and 0.015 mg/L, respectively) resulted in a significan t decrease in cfu, of up to approximately 1 log(10) after 48 h of incubatio n. In contrast, incubation of intraphagocytic L. pneumophila in the presenc e of antibiotics without intracellular activity (ceftizoxime, imipenem or a moxycillin-clavulanic acid) did not have any effect. Azithromycin inhibited intracellular replication at concentrations as low as 0.125 mg/L, approxim ately one-quarter of the extracellular MIC. The Mono Mac 6 cell line is a u seful infection model for investigating the intracellular activity of antim icrobial agents in vitro. In accordance with clinical data and animal exper iments, azithromycin and ciprofloxacin inhibited the intraphagocytic replic ation of L. pneumophila. In particular, azithromycin killed ingested legion ellae in vitro at concentrations below the peak serum concentrations and be low the MIC.