Scheduling collateral sensitivity‐based cycling therapies toward eradication of drug‐resistant infections

Abstract

AbstractDrug resistant pathogens are a global public health threat and their control has become a challenging task. A new health paradigm has been proposed in recent years through clinical research, this is the sequential use of drugs where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity and its converse is known as cross resistance. However, the order and time of cycling between drugs need to be tailored to the pathogen population presented in the host. Here, by abstracting mutation networks of collateral sensitivity based on switched systems, we explore the control theoretical aspects and implications of collateral sensitivity on the impact of eradication of drug‐resistant pathogens. Our numerical simulations illustrate the potential implications of our approach to mitigate drug resistance or even eradicate pathogenic populations.