We examined the effects of the
macrolide antimicrobial agent azithromycin and
phenothiazine compounds against clinical isolates of Acanthamoeba spp. and Balamuthia mandrillaris, opportunistic pathogens of human beings and other animals. Acanthamoeba growth was inhibited in vitro at 1, 5, and 10 micrograms/ml of
azithromycin, but not the
macrolides,
erythromycin, and
clarithromycin. In experiments attempting to simulate in vivo conditions,
azithromycin protected monolayers of rat
glioma cells from destruction by Acanthamoeba at a concentration of 0.1 microgram/ml, and delayed destruction at concentrations of 0.001 and 0.01 microgram/ml. We concluded that the minimal inhibitory concentration of
azithromycin was 0.1 microgram/ml. Our results, however, suggested that the drug was amebastatic but not amebicidal, since ameba growth eventually resumed after drug removal. The
phenothiazines (
chlorpromazine,
chlorprothixene, and
triflupromazine) inhibited Acanthamoeba growth by 70-90% at 5 and 10 micrograms/ml, but some of these compounds were toxic for rat
glioma cells
at 10 micrograms/ml.
Azithromycin was not very effective against B. mandrillaris in an in vitro setting, but was amebastatic in tissue culture monolayers at concentrations of 0.1 microgram/ml and higher. Balamuthia amebas showed in vitro sensitivity to
phenothiazines. Ameba growth was inhibited 30-45% at 5 micrograms/ml in vitro, but completely at 5 micrograms/ml in the rat
glioma model. In spite of their potential as antiamebic drugs in
Balamuthia infections, toxicity of
phenothiazines limits their use in clinical settings.