Microfluidics for Studying Pharmacodynamics of Antibiotics

Rising antibiotic resistance is a significant global health issue with incorrect prescription of antibiotics being one of the major causes. Determination of the minimum inhibitory concentration (MIC) of an antibiotic against pathogens is typically used to determine the appropriate antibiotic dosing regimen before prescription. The conventional methods to determine MIC, however, are tedious, low throughput, and require relatively large sample volumes. Furthermore, MIC is not an optimal parameter since the MIC reflects only an end-point estimate of the effect of an antibiotic on the bacteria without taking into account the time course of action, which in turn leads to unpredictable in vivo results. Microfluidic approaches may be able to address these issues by generating precise time-kill curves in an automated, rapid, and multiplexed fashion using small sample volumes. The ability to generate multiple, precise time-kill curves enables the use of pharmacokinetic and pharmacodynamic (PK/PD) modeling to provide superior metrics for evaluating the antibiotic efficacy and to improve the prediction of in vivo results. In this chapter, we review prior work on microfluidic platforms for antibiotic susceptibility testing (AST) as well as the utilization of microfluidics in combination with PK/PD modeling for AST.