细胞内人类病原体是最致命的传染病，由于其在宿主细胞内的保护作用和抗微生物耐药性（AMR）的发展，因此难以有效治疗。对抗这些细胞内病原体的一种新兴方法是宿主导向疗法（HDT），利用宿主细胞的先天免疫。HDT依赖于小分子来促进最终导致病原体清除的宿主保护机制。这些疗法被假设为1)具有间接但广泛的，跨物种抗菌活性，2）有效靶向耐药病原菌，3)携带对AMR发展的敏感性降低，和4)与常规抗菌剂具有协同作用。随着HDT领域的扩大，这项系统评价是为了收集HDT及其特征的汇编，例如受影响的主机机制，病原体抑制，浓度调查，和病原体抑制的程度。对主要的四个HDT假设的证据支持进行了评估，并得出结论，HDT表现出强大的跨物种活动，对AMR病原体有活性，临床分离株和实验室适应的病原体。然而,存在有限的信息来支持HDT与经典抗菌药物协同作用的观点,并且不太容易发生AMR.
Intracellular human pathogens are the deadliest infectious diseases and are difficult to treat effectively due to their protection inside the host cell and the development of antimicrobial resistance (AMR). An emerging approach to combat these intracellular pathogens is host-directed therapies (HDT), which harness the innate immunity of host cells. HDT rely on small molecules to promote host protection mechanisms that ultimately lead to pathogen clearance. These therapies are hypothesized to: (1) possess indirect yet broad, cross-species antimicrobial activity, (2) effectively target drug-resistant pathogens, (3) carry a reduced susceptibility to the development of AMR and (4) have synergistic action with conventional antimicrobials. As the field of HDT expands, this systematic
review was conducted to collect a compendium of HDT and their characteristics, such as the host mechanisms affected, the pathogen inhibited, the concentrations investigated and the magnitude of pathogen inhibition. The evidential support for the main four HDT hypotheses was assessed and concluded that HDT demonstrate robust cross-species activity, are active against AMR pathogens, clinical isolates and laboratory-adapted pathogens. However, limited information exists to support the notion that HDT are synergistic with canonical antimicrobials and are less predisposed to AMR development.
