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Acoustic manipulation has emerged as a versatile method for microfluidic separation and concentration of particles and cells. Most recent demonstrations of the technology use piezoelectric actuators to excite resonant modes in silicon or glass microchannels. Here, we focus on acoustic manipulation in disposable, plastic microchannels in order to enable a low-cost processing tool for point-of-care diagnostics. Unfortunately, the performance of resonant acoustofluidic devices in plastic is hampered by a lack of a predictive model. In this paper, we build and test a plastic blood-bacteria separation device informed by a design of experiments approach, parametric rapid prototyping, and screening by image-processing. We demonstrate that the new device geometry can separate bacteria from blood while operating at 275% greater flow rate as well as reduce the power requirement by 82%, while maintaining equivalent separation performance and resolution when compared to the previously published plastic acoustofluidic separation device.