Public health case for microbiome-sparing antibiotics and new opportunities for drug development, 2024, L. Clifford McDonald et al

ABSTRACT
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.

PERSPECTIVE
The introduction of antibiotics into clinical practice was a significant medical breakthrough that drastically reduced mortality rates related to infectious disease, increased the average human lifespan, and paved the way for modern procedures that would otherwise not be possible.

Antimicrobial resistance (AR) among microorganisms has expanded over time through selective pressure, leading to more AR infections in humans, and is now a leading cause of mortality globally.

An additional and underappreciated effect of antibiotic use is the collateral damage to our microbiota and resulting antibiotic-induced dysbiosis. In the ongoing search for clinical and public health solutions to the AR crisis, it will be key to develop new classes of antibiotics that combat infections without accelerating the development of resistance, with potential additional benefits of avoiding antibiotic-induced dysbiosis and thereby reducing secondary infections as well as transmission.

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I wonder whether there's much R&D into tailored phages. That might be a good use for genetic engineering.