Antagonistic interactions between spinosad and macrocyclic lactones in combination against larvae of the sheep blowfly, Lucilia cuprina, in vitro

Abstract

Control of the sheep blowfly relies on insecticides, however resistance is currently impacting on their efficacy. The use of insecticides in combination (mixtures) is considered to be a useful strategy to delay resistance under some circumstances. The present study aimed to examine the combination of spinosad with macrocyclic lactones in order to determine if the two drug classes showed any interactions that would impact on the usefulness of a combination product for flystrike control. We used isobologram analysis to examine drug interactions in in vitro bioassays with the larval stages of the sheep blowfly. In initial single drug assays, ivermectin and abamectin showed similar EC₅₀ against blowfly larvae, while moxidectin and spinosad were 20- and 30-fold less potent, respectively. Combinations of spinosad and each of the macrocyclic lactones showed a pattern of interactions dominated by antagonistic or additive relationships when combined at different ratios. Peaks in antagonism were associated with combinations at ratios equivalent to, or close to, the relative EC₅₀s when used alone. The antagonism was strongest for moxidectin, with combination index values up to 1.82 at the EC₅₀ and 3.2 at the EC₉₀ at a spinosad: moxidectin ratio of 0.78:1. Maximum combination index values for ivermectin and abamectin at the EC₉₀ were 1.61 and 1.42, at ratios of 27:1 and 31:1, respectively, indicating a significant degree of antagonism for both combinations. We suggest that the observed antagonism may be due to interactions at common ion channel receptors, although this requires confirmation. The study highlights the need to examine drug interactions as a component of determining the suitability of specific drug combinations for parasite control.