Journal of Antimicrobial Chemotherapy, Vol 42, 761-767, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
F Van Bambeke, C Gerbaux, JM Michot, MB d'Yvoire, JP Montenez and PM Tulkens
Computer-aided simulations suggest that the doses and schedules of
administration of azithromycin proposed in treatment and prophylaxis of
Mycobacterium avium complex (MAC) in AIDS patients will result in drug
concentrations in serum and extracellular fluids remaining for sustained
periods of time in the 0.03-0.1 mg/L range. We exposed cultured rat embryo
fibroblasts to these concentrations (and multiples up to 20 mg/L) for up to
16 days. Electron microscopy showed that after 7 days' incubation in 0.03
mg/L azithromycin, there was conspicuous accumulation of osmiophilic,
lamellar structures (myeloid bodies) in lysosomes, suggesting the onset of
a phospholipidosis. Assay of total cell phospholipids and cholesterol
showed significant increases in cells exposed to > or = 1 to 5 mg/L of
azithromycin in association with hyperactivity of the lysosomal enzyme
cathepsin B. The data suggest that azithromycin, at extracellular
concentrations pertinent to its use for MAC treatment, and perhaps also
prophylaxis, causes limited morphological alterations of the lysosomes in
cultured cells which are of the same nature as those developing rapidly and
extensively at higher concentrations.
Lysosomal alterations induced in cultured rat fibroblasts by long-term exposure to low concentrations of azithromycin [In Process Citation]
Unite de Pharmacologie Cellulaire et Moleculaire, Uinversite Catholique de Louvain, Brussels, Belgium. vanbambeke@facm.ucl.ac.be
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