Host niche-specific challenges hindering the treatment of polymicrobial infections

ABSTRACT Antimicrobial recalcitrance is a growing problem in today’s world. Not only are bacteria developing resistance at an alarming pace but the antibiotic discovery pipeline has gone dry, making antimicrobial stewardship essential for preserving the activity of the antibiotics still currently available for use. In addition to resistance, bacteria also display tolerance to certain treatments as they adapt to their body site-specific niche and cooperate with other organisms in polymicrobial communities. Thus, new and existing antibiotics must contend with altered bacterial metabolism, polymicrobial synergy, increased biofilm production, and nutrient-related adaptations present within specific infectious sites. Finally, these treatments must face the challenging process of moving to the infection site and doing their job without causing harm to the patient. This minireview explores the difficulties antimicrobials face when challenging organisms at different body sites, focusing on the niche-specific dynamics present at sites of infection.