Antimicrobial Therapy in the Context of the Damage-Response Framework: the Prospect of Optimizing Therapy by Reducing Host Damage

By design, antimicrobial agents act directly on microbial targets. These drugs aim to eliminate microbes and are remarkably effective against susceptible organisms. Nonetheless, some patients succumb to infectious diseases despite appropriate antimicrobial therapy. Today, with very few exceptions, physicians select antimicrobial therapy based on its activity against the targeted organism without consideration of how the regimen affects patients' immune responses. An important concept to emerge in the past few decades is that immune responses to microbes can be detrimental by enhancing host damage, which can translate into clinical disease. A central tenet of the damage-response framework (DRF) of microbial pathogenesis is that the relevant outcome of host-microbe interaction is the damage that occurs in the host, which can be due to microbial factors, host factors, or both. Given that host damage can make patients sick, reducing it should be a goal of treating infectious diseases. Inflammation and damage that stem from the host response to an infectious disease can increase during therapy with some antimicrobial agents and decrease during therapy with others. When a patient cannot eliminate a microbe with their own immune response, antimicrobial therapy is essential for microbial elimination, and yet it can affect the inflammatory response. In this essay, we discuss antimicrobial therapy in the context of the DRF and propose that consideration of the DRF may help tailor therapy to a patient's need to augment or reduce inflammation.