Additivity of inhibitory effects in multidrug combinations.

ABSTRACT: From natural ecology^1-4 to clinical therapy^5-8, cells are often exposed to mixtures of multiple drugs. Two competing null models are used to predict the combined effect of drugs: response additivity (Bliss) and dosage additivity (Loewe)^9-11. Here, noting that these models diverge with increased number of drugs, we contrast their predictions with growth measurements of four phylogenetically distant microorganisms including Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Saccharomyces cerevisiae, under combinations of up to ten different drugs. In all species, as the number of drugs increases, Bliss maintains accuracy while Loewe systematically loses its predictive power. The total dosage required for growth inhibition, which Loewe predicts

SUBMITTER: Russ D 

PROVIDER: S-EPMC6295580 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature