Invasive fungal infection in patients with hematologic disorders in a Brazilian tertiary care hospital

ABSTRACT INTRODUCTION: Invasive fungal infections (IFIs) are an important complication in immunocompromised individuals, particularly neutropenic patients with hematological malignancies. In this study, we aimed to verify the epidemiology and diagnosis of IFIs in patients with hematologic problems at a tertiary hospital in Goiânia-GO, Brazil. METHODS: Data from 117 patients, involving 19 cases of IFIs, were collected. The collected data included diagnosis methods, demographics, clinical characteristics, and in vitro susceptibility to different antifungal agents. Among the 19 cases, 12 were classified as proven IFI and 7 as probable invasive aspergillosis with detection of galactomannan in blood and presence of lung infiltrates in radiographic images. Logistic regression analysis showed that the proven and probable IFIs were associated with increased risk of death. Statistical analysis demonstrated that age, sex, and underlying disease were not independently associated with risk of death in IFI patients. RESULTS: Most bloodstream isolates of Candida spp. exhibited low minimum inhibitory concentrations (MICs) to all antifungal agents tested. Voriconazole and amphotericin had the lowest MICs for Aspergillus spp. and Fusarium spp., but Fusarium spp. showed the least susceptibility to all antifungals tested. Amphotericin B, fluconazole, and itraconazole were found to be inactive in vitro against Acremonium kiliense; but this fungus was sensitive to voriconazole. CONCLUSIONS: Considering the high number of IFI cases, with crude mortality rate of 6%, we could conclude that IFIs remain a common infection in patients with hematological malignancies and underdiagnosed ante mortem. Thus, IFIs should be monitored closely.

引言：侵袭性真菌感染（Invasive fungal infections, IFIs）是免疫功能低下人群，尤其是合并血液系统恶性肿瘤的中性粒细胞减少患者的重要并发症。本研究旨在明确巴西戈亚尼亚市某三级医院内血液系统疾病患者侵袭性真菌感染的流行病学特征与诊断方案。

方法：本研究共收集117例患者的临床资料，其中19例确诊为侵袭性真菌感染。收集的资料涵盖诊断方法、人口学特征、临床特征以及各类抗真菌药物的体外药敏结果。在19例患者中，12例为确诊侵袭性真菌感染，7例为拟诊侵袭性曲霉病，此类患者血液半乳甘露聚糖（galactomannan）检测呈阳性，且影像学检查可见肺部浸润影。Logistic回归分析显示，确诊及拟诊侵袭性真菌感染与死亡风险升高显著相关。统计学分析表明，年龄、性别及基础疾病与侵袭性真菌感染患者的死亡风险无独立相关性。

结果：大部分念珠菌属（Candida spp.）血流分离株对所有受试抗真菌药物的最低抑菌浓度（minimum inhibitory concentrations, MICs）均处于较低水平。伏立康唑（voriconazole）与两性霉素（amphotericin）对曲霉属（Aspergillus spp.）和镰刀菌属（Fusarium spp.）的最低抑菌浓度最低，但镰刀菌属对所有受试抗真菌药物的敏感性最差。体外药敏实验显示，两性霉素B（amphotericin B）、氟康唑（fluconazole）及伊曲康唑（itraconazole）对顶孢霉（Acremonium kiliense）无体外抗菌活性，但该菌对伏立康唑敏感。

结论：本研究中侵袭性真菌感染病例占比颇高，粗死亡率达6%，据此可得出结论：侵袭性真菌感染仍是血液系统恶性肿瘤患者的常见感染类型，且生前诊断率偏低。因此，需对侵袭性真菌感染开展密切监测。