National Aspergillosis Centre, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, UK.
Division of Infection, Inflammation and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Mycoses. 2020 Apr;63(4):376-381. doi: 10.1111/myc.13052. Epub 2020 Feb 5.
Chronic pulmonary aspergillosis (CPA) is a progressive respiratory disease, caused most commonly by A fumigatus, with significant morbidity and mortality. Azole resistance in A fumigatus is a growing concern worldwide, with resistance to itraconazole reported in up to 50% of patients.
The aim of this study was to determine whether a positive Aspergillus PCR (polymerase chain reaction) is a marker of resistance in CPA patients on azole therapy.
Patients were selected via a consecutive database search for the first 50 CPA patients with a positive Aspergillus PCR from January to September 2016. Data were collected regarding concurrent and subsequent culture results, current therapy and serum antifungal levels. PCR-positive patients not on therapy were included as the control group.
Twenty-three patients were on therapy (15 itraconazole, 4 voriconazole and 4 posaconazole). Cycle threshold (Ct) values ranged from 20.8 to 37.9; no significant difference was found between each treatment and the control group (P = .47). In treated patients, concurrent azole-resistant A fumigatus was found in 75% of A fumigatus-positive cultures (6/8). All of the resistant isolates in the itraconazole group showed therapy resistance. Twenty per cent of all itraconazole levels were sub-therapeutic. No significant difference was found in serum itraconazole levels for patients on itraconazole with a positive PCR versus negative PCR (P = .44).
Positive sputum, Aspergillus-specific PCR can be associated with azole resistance in CPA patients on therapy.
慢性肺曲霉病（CPA）是一种进行性呼吸系统疾病，最常见的病原体是烟曲霉，具有较高的发病率和死亡率。烟曲霉对唑类药物的耐药性是一个全球性的问题，据报道，多达 50%的患者对伊曲康唑耐药。
本研究旨在确定在唑类药物治疗的 CPA 患者中，曲霉 PCR（聚合酶链反应）阳性是否是耐药的标志物。
通过连续数据库搜索，选择了 2016 年 1 月至 9 月期间前 50 例曲霉 PCR 阳性的 CPA 患者。收集了关于同期和后续培养结果、当前治疗和血清抗真菌水平的数据。未接受治疗但 PCR 阳性的患者被纳入对照组。
23 例患者正在接受治疗（15 例伊曲康唑、4 例伏立康唑和 4 例泊沙康唑）。Ct 值范围为 20.8 至 37.9；每个治疗组与对照组之间无显著差异（P=0.47）。在接受治疗的患者中，75%的曲霉阳性培养物中发现了与唑类药物耐药相关的烟曲霉（6/8）。伊曲康唑组的所有耐药分离株均表现出治疗耐药性。20%的伊曲康唑水平低于治疗水平。伊曲康唑治疗的患者中，PCR 阳性与 PCR 阴性患者的血清伊曲康唑水平无显著差异（P=0.44）。
在接受治疗的 CPA 患者中，痰液阳性、曲霉特异性 PCR 可能与唑类药物耐药相关。
