Efficacy of Novel Antimicrobials Against Clinical Isolates of Opportunistic Amebas

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.