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Study on invasive aspergillosis using galactomannan enzyme immunoassay and determining antifungal drug susceptibility among hospitalized patients with hematologic malignancies or candidates for organ transplantation.
Microbial Pathogenesis ( IF 3.8 ) Pub Date : 2020-07-12 , DOI: 10.1016/j.micpath.2020.104382
Pegah Ardi 1 , Roshanak Daie-Ghazvini 1 , Seyed Jamal Hashemi 2 , Mohammad Reza Salehi 3 , Heidar Bakhshi 1 , Zahra Rafat 1 , Mahdi Zareei 4 , Muhammad Getso 1 , Solmaz Basiri 1 , Hasti Kamali Sarwestani 1 , Zeinab Borjian Boroujeini 1 , Kazem Ahmadikia 1
Affiliation  

The incidence of invasive aspergillosis (IA) has dramatically increased during the last decade. This infection is associated with high morbidity and mortality, ranging from 30% to 70%, especially in immunocompromised patients. Delay in diagnosis and treatment is usually associated with high mortality rates. This study was aimed to assess the diagnostic value of Galactomannan EIA (GM) for early diagnosis of aspergillosis in hospitalized patients with underlying conditions. Also, the antifungal drug susceptibility profiles of causative agents were investigated. In this descriptive cross-sectional study, during the period of 18 months starting from September 2017 until February 2019, 22 bronchoalveolar lavage (BAL) and 13 biopsies from infected sinuses were obtained from a total of 150 patients suffering from different types of hematologic malignancies. All the samples were subjected to microscopic examination and fungal culture. Also, serum specimens were obtained from all patients (n = 135). 22 serum and 17 BAL specimens were tested for the GM level. Fungal identified were confirmed through the PCR-sequencing of the β-tubulin gene. The susceptibility to amphotericin B, itraconazole, voriconazole, posaconazole, ravuconazole, and caspofungin was evaluated according to the Clinical and Laboratory Standards Institute document M38-A2 (CLSI M38-A2) broth microdilution protocol. The results showed that the incident rate of IA was 23.33% and 35 patients with IA (12 proven cases and 23 probable cases) were diagnosed according to the European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria. The 35 patients with IA in the current study comprised 19 men (54.29%) and 16 women (45.71%) with the median age of 42 years. AML (31.5%) was documented as the most prevalent risk factor among our subjects with IA and Aspergillus flavus (65.7%) was the most prevailing causal agent in this study. Among patients with IA, ague (71%) and cough (60%) were the most common symptoms. In the present study, a sensitivity of 94% and a specificity of 98% was reported for GM ELISA in BAL specimens. Also, a sensitivity of 58% and a specificity of 98% was reported for GM ELISA in serum samples. Among 6 tested antifungal drugs, the lowest minimum inhibitory concentration (MIC) values were observed for posaconazole and ravuconazole which showed the range of 0.008–0.0062 μgml and 0.031–0.125 μgml, respectively. The current study has demonstrated that determining the value of GM investigation in BAL and serum specimens can be promising in early diagnosis of IA, also molecular identification of the agents causing IA and their antifungal susceptibility patterns are essential issues for the targeted antifungal therapy and outcome improvement of patients with this life-threatening disease.



中文翻译:

应用半乳甘露聚糖酶免疫分析法对侵袭性曲霉病进行研究,并确定住院的血液系统恶性肿瘤患者或器官移植患者的抗真菌药敏感性。

在过去十年中,侵袭性曲霉病(IA)的发病率急剧上升。这种感染与高发病率和高死亡率相关,从30%到70%不等,尤其是在免疫功能低下的患者中。延迟诊断和治疗通常与高死亡率相关。这项研究旨在评估半乳甘露聚糖EIA(GM)对基础疾病住院患者曲霉病的早期诊断价值。此外,还研究了病原菌的抗真菌药敏性。在此描述性横断面研究中,从2017年9月到2019年2月,为期18个月,从总共150例患有不同类型血液恶性肿瘤的患者中获得22支支气管肺泡灌洗(BAL)和13份感染鼻窦活检。对所有样品进行显微镜检查和真菌培养。另外,从所有患者中获得血清标本(n = 135)。测试了22个血清和17个BAL标本的GM水平。通过β-微管蛋白基因的PCR测序确认了鉴定出的真菌。根据临床和实验室标准协会文件M38-A2(CLSI M38-A2)肉汤微量稀释方案评估两性霉素B,伊曲康唑,伏立康唑,泊沙康唑,拉伏康唑和卡泊芬净的敏感性。结果表明,IA的发生率为23。根据欧洲癌症和真菌病研究与治疗组织标准,诊断出33%的IA患者(35例确诊病例和23例可能病例)。本研究中的35例IA患者包括19位男性(54.29%)和16位女性(45.71%),中位年龄为42岁。AML(31.5%)被证明是我们IA和IA患者中最普遍的危险因素黄曲霉(65.7%)是该研究中最主要的病原体。在IA患者中,最常见的症状是ague(71%)和咳嗽(60%)。在本研究中,据报道BAL标本中GM ELISA的敏感性为94%,特异性为98%。另外,据报道血清样品中GM ELISA的敏感性为58%,特异性为98%。在6种经过测试的抗真菌药物中,泊沙康唑和拉伏康唑的最低最低抑菌浓度(MIC)值最低,为0.008–0.0062。μG 和0.031–0.125 μG, 分别。目前的研究表明,确定BAL和血清标本中的GM研究的价值对于IA的早期诊断可能很有希望,而且引起IA的药物的分子鉴定及其抗真菌药性模式对于靶向抗真菌治疗和改善结局至关重要。患有这种威胁生命的疾病的患者

更新日期:2020-07-13
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