Host-Directed Therapy in Nontuberculous Mycobacterial Pulmonary Disease: Preclinical and Clinical Data Review

Standard treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD) infection involves a multi-drug antimicrobial regimen for at least 12 months. The length, complexity, and side effect profile of antibiotic therapy for NTM-PD pose significant difficulties for maintaining patient adherence. Furthermore, physician adherence to NTM guidelines suffers for similar reasons to the extent that a study evaluating treatment approaches across multiple specialties found that only 13% of antibiotic regimens met ATS/IDSA guidelines. For this reason, a great need exists for therapy that augments the current armamentarium of antimicrobial chemotherapeutics or provides an alternative approach for decreasing host mycobacterial burden. As our knowledge of the mechanisms driving protective responses to NTM-PD infections by mammalian hosts expand, these processes provide novel therapeutic targets. These agents, which are commonly referred to as host-directed therapies (HDTs) have the potential of providing the much-needed boost to the nontuberculous mycobacterial therapeutic pipeline. In this review, we will focus on translational research and clinical trial data that detail the creation of therapeutic modalities developed to improve host mechanical protection and immunologic responses to PNTM infection.