Synergy of four macrolide antibiotics with chloroquine against chloroquine-resistant Plasmodium falciparum in vitro.
The antimalarial activity of four macrolide antibiotics was investigated against the multidrug resistant K1 strain of Plasmodium falciparum in vitro. ID50 (50% inhibitory concentration) values for erythromycin, spiramycin, tylosin tartrate and oleandomycin phosphate in 48-hour assays were 1.6 X 10(-4)M, 2.5 X 10(-5)M, 1.2 X 10(-5)M and 9 X 10(-6)M respectively, and in 96 hour assays were 10(-5)M, 2.6 X 10(-6)M, 2.6 X 10(-6) and 3 X 10(-6)M, respectively. Comparable values were obtained in assays in which drug effect was quantified from either parasite counts or 14C isoleucine incorporation. Each of the four macrolides displayed synergy with chloroquine at the IC90 (90% inhibitory concentration) level, but at the IC50 level synergy was either less pronounced or absent. For each combination this difference in the degree of synergy was significant at the 95% level of confidence. In replicate assays in which 3H hypoxanthine was the marker of drug effect, synergy between chloroquine and either erythromycin or spiramycin could not be detected.
Gershon
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D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004917:Erythromycin / Q000494:pharmacology; D007933:Leucomycins / Q000494:pharmacology; D009827:Oleandomycin / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D015645:Tylosin
D000962:Antimalarials; D007933:Leucomycins; D004917:Erythromycin; D002738:Chloroquine; D009827:Oleandomycin; D015645:Tylosin