Infectious Diseases Unit, S. Orsola-Malpighi Hospital, Department of Medical and Surgical Sciences, University of Bologna, Italy.
Department of Medical Microbiology, Radboud University Medical Center.
J Infect Dis. 2017 Aug 15;216(suppl_3):S466-S473. doi: 10.1093/infdis/jix222.
Infections caused by triazole-resistant Aspergillus fumigatus are associated with a higher probability of treatment failure and mortality. Because clinical experience in managing these infections is still limited, mouse models of invasive aspergillosis fulfill a critical void for studying treatment regimens designed to overcome resistance. The type of immunosuppression, the route of infection, the timing of antifungal administration, and the end points used to assess antifungal activity affect the interpretation of data from these models. Nevertheless, these models provide important insights that help guide treatment decisions in patients with triazole-resistant invasive aspergillosis. Animal models confirmed that a high triazole minimal inhibitory concentration corresponded with triazole treatment failure and that the efficacy of other classes of drugs, such as the polyenes and echinocandins, was not affected by the presence of triazole resistance mutations. Furthermore, the feasibility of triazole dose escalation, combination therapy, and prophylaxis were explored as strategies to overcome resistance.
由唑类药物耐药烟曲霉引起的感染与治疗失败和死亡率升高的可能性更高有关。由于管理这些感染的临床经验仍然有限，因此侵袭性曲霉病的小鼠模型填补了研究旨在克服耐药性的治疗方案的关键空白。免疫抑制的类型、感染途径、抗真菌药物的给药时间以及用于评估抗真菌活性的终点都会影响对这些模型数据的解释。尽管如此，这些模型提供了重要的见解，有助于指导耐唑类药物侵袭性曲霉病患者的治疗决策。动物模型证实，较高的唑类药物最小抑菌浓度与唑类药物治疗失败相关，并且其他类别的药物（如多烯类和棘白菌素类）的疗效不受唑类耐药突变的影响。此外，还探讨了唑类药物剂量递增、联合治疗和预防作为克服耐药性的策略的可行性。
