Public health case for microbiome-sparing antibiotics and new opportunities for drug development.

Although antibiotics remain a cornerstone of modern medicine, the issues of widespread antibiotic resistance and collateral damage to the microbiome from antibiotic use are driving a need for drug developers to consider more tailored, patient-directed products to avoid antibiotic-induced perturbations of the structure and function of the indigenous microbiota. This perspective summarizes a cascade of microbiome health effects that is initiated by antibiotic-mediated microbiome disruption at an individual level and ultimately leads to infection and transmission of multidrug-resistant pathogens across patient populations. The scientific evidence behind each of the key steps of this cascade is presented. The interruption of this cascade through the use of highly targeted, microbiome-sparing antibiotics aiming to improve health outcomes is discussed. Further, this perspective reflects on some key clinical trial design and reimbursement considerations to be addressed as part of the drug development path.