Abstract：
BACKGROUND: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis.
METHODS: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis.
RESULTS: Ninety-five patients were included, with \"proven\" (n = 27), \"probable\" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and \"possible\" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality.
CONCLUSIONS: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.
METHODS: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis.
RESULTS: Ninety-five patients were included, with \"proven\" (n = 27), \"probable\" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and \"possible\" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality.
CONCLUSIONS: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.
摘要：
背景：新的诊断方法和抗真菌策略可以改善毛霉菌病的预后。我们描述了宏基因组下一代测序（mNGS）的诊断价值，并确定了毛霉菌病的预后因素。
方法：我们对接受单药治疗[两性霉素B(AmB)或泊沙康唑]或联合治疗(AmB和泊沙康唑)的血液病患者进行了回顾性研究。主要结果是诊断后84天全因死亡率。
结果：纳入95例患者，带有“已证明”（n=27），“可能”（n=16）通过传统诊断方法确认的毛霉菌病，和“可能”（n=52）mNGS结果阳性的毛霉菌病。84天死亡率为44.2%。可能+mNGS患者和可能患者的诊断过程相似，总生存率（44.2%vs50.0%，p=0.685）和对有效药物的总体反应率（44.0%vs37.5%，p=0.647)。此外，可能+mNGS患者的中位诊断时间比确诊和可能患者短(14vs26天,p<0.001)。与单一疗法相比，联合疗法在治疗后6周具有更好的生存率（78.8％vs53.1％，p=0.0075)。多因素分析显示联合治疗是保护因素(HR=0.338,95%CI:0.162-0.703,p=0.004),尽管糖尿病（HR=3.864，95％CI：1.897-7.874，p<0.001）和低氧血症（HR=3.536，95％CI：1.874-6.673，p<0.001）是死亡的危险因素。
结论：毛霉菌病是一种危及生命的感染。糖尿病和低氧血症的早期治疗可以改善预后。探索有效的诊断和治疗方法很重要,联合抗真菌治疗似乎具有潜在的益处。
方法：我们对接受单药治疗[两性霉素B(AmB)或泊沙康唑]或联合治疗(AmB和泊沙康唑)的血液病患者进行了回顾性研究。主要结果是诊断后84天全因死亡率。
结果：纳入95例患者，带有“已证明”（n=27），“可能”（n=16）通过传统诊断方法确认的毛霉菌病，和“可能”（n=52）mNGS结果阳性的毛霉菌病。84天死亡率为44.2%。可能+mNGS患者和可能患者的诊断过程相似，总生存率（44.2%vs50.0%，p=0.685）和对有效药物的总体反应率（44.0%vs37.5%，p=0.647)。此外，可能+mNGS患者的中位诊断时间比确诊和可能患者短(14vs26天,p<0.001)。与单一疗法相比，联合疗法在治疗后6周具有更好的生存率（78.8％vs53.1％，p=0.0075)。多因素分析显示联合治疗是保护因素(HR=0.338,95%CI:0.162-0.703,p=0.004),尽管糖尿病（HR=3.864，95％CI：1.897-7.874，p<0.001）和低氧血症（HR=3.536，95％CI：1.874-6.673，p<0.001）是死亡的危险因素。
结论：毛霉菌病是一种危及生命的感染。糖尿病和低氧血症的早期治疗可以改善预后。探索有效的诊断和治疗方法很重要,联合抗真菌治疗似乎具有潜在的益处。
