(159t) Discerning in Vitro Pharmacodynamics from Optical Density Measurements: A Model-Based Approach

Determining the pharmacodynamics of an infectious bacterial population exposed to antibiotics in vitro can provide guidance towards the design of effective therapies for challenging clinical infections. However, accomplishing this task by conducting detailed time-kill experiments is resource-limited, therefore typically bypassed in favor of empirical shortcuts. The resource limitation could be addressed by continuously assessing the size of a bacterial population under antibiotic exposure using optical density measurements over time. However, such measurements count both live and dead cells and, while usable with growing bacterial populations, they cannot assess the size of a declining population of live cells. This work fills this void by developing a model-based method that uses combined counts of both live and dead cells to infer the number of live cells in a bacterial population exposed to antibiotics. Thus, the in vitro pharmacodynamics of the interaction between bacterial population and antibiotics can be easily discerned, and therapy can be guided. The method is general enough for populations comprising bacteria of varying degrees of susceptibility to one or multiple antibiotics, makes no assumptions about the underlying mechanisms that confer resistance, and is applicable to any microbial population whose monitoring, under exposure to antimicrobial agents, yields combined counts of live and dead cells. Use of the model-based method is demonstrated by an experimental study on the response of Acinetobacter baumannii exposed to levofloxacin.