Predictability of the time-dependent toxicities of aminoglycoside antibiotic mixtures to Vibrio qinghaiensis sp.-Q67

Whether the toxicities of aminoglycoside (AG) antibiotics in aquatic environments and their mixtures change with time and whether AG antibiotic mixtures exhibit a toxicological interaction are seldom reported. In this paper, four AG antibiotics, apramycin sulfate, dihydrostreptomycin, kanamycin sulfate, and neomycin sulfate, were selected as mixture components to construct six binary mixture systems. Five rays with different concentration ratios were designed by using the direct equipartition ray design procedure for each system. The toxicities of single antibiotics and their binary mixtures to Vibrio qinghaiensis sp.-Q67 (V. qinghaiensis) at five time points, 0.25, 2, 4, 8 and 12 h, were determined by the time-dependent microplate toxicity analysis method. It was found that the AG antibiotics and their binary mixtures have time-dependent toxicity to V. qinghaiensis, i.e., their toxicities increase with time. Taking the concentration addition as an additive reference, we found that the toxicities of all mixtures are concentration additive, in other words, the additivity does not change with time, concentration, and concentration ratio.