Currently available and recommended options for the treatment of pulmonary aspergillosis include the triazoles, echinocandins, and amphotericin B products. These therapies have significant limitations. Only the azoles are available orally, but their use is often limited by toxicities, drug–drug interactions, pharmacokinetic variability, and emerging resistance. While the echinocandins are safe agents and may have a role in combination therapy, they are unproven as monotherapy. Amphotericin B preparations are toxic and require intensive monitoring. Finally, aspergillosis continues to be a disease conferring substantial morbidity and mortality, and clinical trials have not identified a therapeutic approach clearly associated with improved outcomes. As a result, there is a great need for new options in the treatment of invasive aspergillosis. Ideally, such options would be safe, have high oral bioavailability, have favorable pharmacokinetics to sequestered sites and retain activity against azole-resistant isolates. Reassuringly, there is a robust pipeline of novel therapies in development. Rezafungin (a once-weekly dosed echinocandin) and ibrexafungerp (oral agent with same mechanism of action as echinocandins) will likely be reserved for combination therapy or refractory/intolerance scenarios with no other options. Inhaled opelconazole is an attractive option for combination therapy and prophylaxis of pulmonary aspergillosis. Development of an oral form of amphotericin B that avoids nephrotoxicity and electrolyte disturbances is an exciting development. Finally, olorofim and fosmanogepix, two agents with novel mechanisms of action and oral formulations, hold significant potential to challenge the triazole antifungals place as preferred therapies. However, many questions remain regarding these novel agents, and at the time of this writing, none of these agents have been robustly studied in Phase III studies of aspergillosis, and so their promise remains investigational.

目前可用和推荐的治疗肺曲霉病的选择包括三唑类、棘白菌素类和两性霉素 B 产品。这些疗法有很大的局限性。只有唑类药物可以口服，但它们的使用通常受到毒性、药物间相互作用、药代动力学变异性和新出现的耐药性的限制。虽然棘白菌素是安全的药物并且可能在联合治疗中发挥作用，但它们作为单一疗法尚未得到证实。两性霉素 B 制剂有毒，需要严密监测。最后，曲霉病仍然是一种具有很高发病率和死亡率的疾病，临床试验尚未确定与改善结果明显相关的治疗方法。因此，非常需要治疗侵袭性曲霉菌病的新选择。理想情况下，此类选择应该是安全的，具有高口服生物利用度，对隔离位点具有有利的药代动力学，并保留针对唑类抗性分离株的活性。令人欣慰的是，有大量新疗法正在开发中。Rezafungin（一种每周一次的棘白菌素）和 ibrexafungerp（与棘白菌素具有相同作用机制的口服药物）可能会保留用于联合治疗或难治性/不耐受情况而没有其他选择。吸入奥培​​康唑是联合治疗和预防肺曲霉病的一个有吸引力的选择。开发可避免肾毒性和电解质紊乱的口服两性霉素 B 是一项令人兴奋的进展。最后，奥洛罗芬和fosmanogepix这两种具有新颖作用机制和口服制剂的药物，具有挑战三唑类抗真菌药物作为首选疗法的巨大潜力。然而，关于这些新型药物仍然存在许多问题，并且在撰写本文时，这些药物都没有在曲霉菌病的 III 期研究中进行过深入研究，因此它们的前景仍处于研究阶段。