Host Directed Therapies in Microbial Infections: A New Frontier for Emergency Care, Implementation, Challenges and Future Directions

Abstract

Microbial infections become one of the major worldwide health issues due to new trends in antibiotic resistance, limitations in conventional therapies. The concept of Host-Directed Therapies (HDTs) is aimed at a novel approach. These HDTs emphasize modulating the host immune and cellular pathways to fight an infection, which is distinctly different from traditional antimicrobial agents. They eliminate selective pressures that may give rise to antibiotic resistance and provide broad-spectrum efficacy. These treatments exploit mechanisms including immune modulation, pathogen exploitation of host pathways inhibition, and tissue repair.
Recent developments in HDTs include small molecules, monoclonal antibodies, and RNA-based therapeutics that are highly effective against viral, bacterial, and fungal pathogens. These are exemplified by the interleukin modulators used to augment host immune responses and by host protein hijackers targeted by these drugs. However, some of the challenges HDTs are facing include the possibility of off-target effects, expensive development, and the variability in host genetic response. This review includes the mechanistic basis, their therapeutic applications, and ongoing challenges of HDTs with respect to the management of microbial infections. We outline recent studies that focus upon their potential in the management of MDRI, sepsis, and emerging pathogens. Finally, to give an overview of this promising therapeutic paradigm, we have discussed the integration of HDTs with traditional antimicrobial therapies and emerging technologies such as nanotechnology and artificial intelligence.