Treatment with Fluticasone Propionate Increases Antibiotic Efficacy during Treatment of Late-Stage Primary Pneumonic Plague.
Treatment with Fluticasone Propionate Increases Antibiotic Efficacy during Treatment of Late-Stage Primary Pneumonic Plague.
复制标题
丙酸氟替卡松治疗可增加晚期原发性鼠疫的抗生素疗效。
DOI：
10.1128/aac.01275-21
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发表时间：
2022-01-18
影响因子：
4.9
通讯作者：
Pechous RD
中科院分区：
文献类型：
--
作者：
Crane SD;Banerjee SK;Pechous RD
严重和晚期肺炎通常难以单独用抗生素治疗，因为宿主对明确感染的炎症反应压倒性。这些宿主反应导致肺损伤，导致急性肺损伤、急性呼吸窘迫综合征和死亡。为了有效地治疗严重和晚期肺炎，必须考虑使用预防性治疗，以减少肺损伤时，抗菌药物可以管理。鼠疫是一种由吸入鼠疫耶尔森氏菌引起的严重肺炎，是一种致命的疾病，在没有抗生素干预的情况下，6天内就会导致死亡。晚期肺鼠疫很难治疗，因为抗生素必须在症状出现后24小时内提供才能有效。在这里，我们使用原发性肺鼠疫的小鼠模型来研究宿主炎症反应如何影响晚期肺鼠疫的抗生素治疗。我们建立了一个小鼠感染模型，证明了与抗生素延迟给药相关的不良结局。我们发现，鼻内丙酸氟替卡松预处理小鼠增加了延迟抗生素给药的疗效，并提高了小鼠的存活率。接受丙酸氟替卡松的小鼠也显示出肺中细菌负荷减少和炎症病理减少。此外，我们发现治疗和生存率与白细胞介素-6（IL-6）水平降低和中性粒细胞浸润减少相关。这项工作证明了宿主炎症反应如何使晚期肺鼠疫的治疗复杂化，并表明靶向宿主炎症反应可能会改善严重晚期肺炎的治疗。
Severe and late-stage pneumonias are often difficult to treat with antibiotics alone due to overwhelming host inflammatory responses mounted to clear infection. These host responses contribute to pulmonary damage leading to acute lung injury, acute respiratory distress syndrome, and death. In order to effectively treat severe and late-stage pneumonias, use of adjunctive therapies must be considered to reduce pulmonary damage when antimicrobial agents can be administered. Pneumonic plague, a severe pneumonia caused by inhalation of Yersinia pestis, is a fatal disease that causes death within 6 days without antibiotic intervention. Late-stage pneumonic plague is difficult to treat, as antibiotics must be delivered within 24 h after onset of symptoms to be effective. Here, we use a murine model of primary pneumonic plague to examine how host inflammatory responses impact antibiotic treatment of late-stage pneumonic plague. We developed a murine infection model demonstrating the poor outcomes associated with delayed delivery of antibiotics. We show that pretreatment of mice with intranasal fluticasone propionate increased the efficacy of delayed antibiotic delivery and enhanced murine survival. Mice receiving fluticasone propionate also showed decreased bacterial burden and reduced inflammatory pathology in the lungs. Further, we show that treatment and survival correlated with decreased levels of interleukin-6 (IL-6) and reduced neutrophil infiltration to the lungs. This work demonstrates how host inflammatory responses complicate treatment of late-stage pneumonic plague and suggests that targeting of host inflammatory responses may improve treatment of severe, late-stage pneumonia.