The National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
The National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK; The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Int J Antimicrob Agents. 2018 Aug;52(2):258-264. doi: 10.1016/j.ijantimicag.2018.06.001. Epub 2018 Jun 12.
Chronic pulmonary aspergillosis (CPA) is a progressive infection that destroys lung tissue in non-immunocompromised patients. First-line therapies for CPA (itraconazole and/or voriconazole) are often curtailed due to toxicity or the development of drug resistance. Posaconazole is a potential alternative for these patients.
Use of posaconazole was funded by the National Health Service Highly Specialised National Commissioners on an individual basis for patients who failed or did not tolerate first-line therapy; those who met predefined criteria for improvement at 4 and 6 months (weight gain and/or improvement in St George's Respiratory Questionnaire) continued posaconazole long-term. We recorded response, failure, discontinuation rates, and adverse events.
Seventy-eight patients received posaconazole as salvage therapy. Thirty-four (44%) achieved targets for continuation of therapy. Fourteen (18%) failed therapy; five (36%) patients did not achieve clinical targets at 4 or 6 months of assessment and nine (64%) developed clinical and/or radiological failure. Twenty-eight (36%) discontinued their trial early; 8 (29%) died and 20 (71%) had significant side effects. One patient was non-compliant and another was lost to follow up.
Establishing criteria for therapeutic success offered a clear, safe and sustainable method of identifying patients who benefit from additional therapy, and minimised continuation of ineffective therapy in those who did not.
慢性肺曲霉病（CPA）是一种进行性感染，会破坏非免疫功能低下患者的肺部组织。CPA 的一线治疗药物（伊曲康唑和/或伏立康唑）由于毒性或耐药性的发展而经常被中断。泊沙康唑是这些患者的潜在替代药物。
英国国家医疗服务体系（NHS）根据患者的具体情况，以个体为基础，为那些一线治疗失败或不耐受的患者提供泊沙康唑治疗；那些在第 4 个月和第 6 个月时满足体重增加和/或圣乔治呼吸问卷改善等预先设定的标准的患者，继续接受长期的泊沙康唑治疗。我们记录了应答、失败、停药率和不良反应。
78 名患者接受泊沙康唑作为挽救性治疗。34 名（44%）患者达到了继续治疗的目标。14 名（18%）患者治疗失败；5 名（36%）患者在第 4 个月或第 6 个月的评估中未达到临床目标，9 名（64%）患者出现临床和/或影像学失败。28 名（36%）患者提前终止了试验；8 名（29%）患者死亡，20 名（71%）患者出现严重不良反应。1 名患者不遵医嘱，另 1 名患者失访。
确立治疗成功的标准为识别从额外治疗中获益的患者提供了一种清晰、安全和可持续的方法，并最大限度地减少了那些未获益患者继续无效治疗的可能性。
