曲霉菌感染--- ICU患者的高危因素

曲霉菌病感染--- ICU患者的高危因素

侵袭性曲霉菌病（Invasive Aspergillosis , IA）是曲霉菌感染人体致病最严重的一种形式。对于ICU的危重患者，有报道的IA的发病率高达10%，1这个数字要高于以往其他疾病人群所报道的数字0.33-6.9%。2事实上，在ICU患者中，IA的危险因素有很多，不仅仅限于由EORTC/MSG指南中提到的单一的宿主因素。比如，长期糖皮质激素治疗的患者，慢性阻塞性肺病（Chronic Obstructive Pulmonary Disease, COPD），肝硬化，实体器官肿瘤，HIV感染，肺移植，以及较长时间的ICU住院（大于21天）等。3两项针对COPD患者伴发IA研究分析发现，这类患者的临床结局都非常差，死亡率均达到了100%。4,5在2014年另一项研究中，COPD伴发IA的死亡率为66%。1 在欧洲癌症研究和治疗组织和真菌病研究组（European Organization for Research and Treatment Cancer and Mycoses Study Group, EORTC/MSG）的标准中，类固醇使用超过三周以上被认为是IA的危险因素。对于严重的和/或持续的败血性休克患者，使用低剂量的类固醇（盐皮质激素）可以改善临床结局。6但它们也对巨噬细胞杀伤曲霉菌孢子和单核细胞杀伤曲霉菌菌丝的作用存在损害。7 对于有肺部疾病的患者，即使使用低剂量的类固醇，其伴发IA的风险也会更高。8对于肝硬化患者，由于其细胞吞噬作用和趋化作用受损，被认为是导致IA发病的可能因素。9

由于ICU患者伴发IA有较高的发病率和死亡率，建立可以实现早期诊断的检测方法或诊断标准就非常有意义。血清曲霉菌抗或半乳甘露聚糖（galactomannan, GM）是有报道的血液肿瘤患者中IA检测的可靠手段。10 GM检测比较于其他方法，可以帮助临床提早8天诊断IA。11血清GM抗原是曲霉菌细胞壁的多糖成分，在曲霉菌菌丝侵袭机体组织时释放。这个成分可通过一步夹心酶联免疫法进行检测。近年的一些研究证实，在血液肿瘤患者中，由于GM水平升高与较差的临床结局呈强相关，因此认为GM抗原检测也可作为IA临床结局的衡量工具。12,13

GM抗原检测所使用的试剂为Bio-Rad公司的曲霉菌抗原检测试剂盒（Platelia TM Aspergillus Ag），该试剂为一步夹心酶联免疫法，利用单克隆抗体（EBA-2）对血液循环中的GM抗原。推荐首次检测时间点一般为当临床怀疑患者发生IA时，或者需要对免疫妥协患者进行常规筛查时。1 另外，对于开始进行抗真菌治疗的患者，推荐进行每周两次的GM水平监测，以帮助判断临床疗效及患者预后。14

1. Suzanne Teering, Annelies Verreth, Anneleen Peeter, et al Prognostic value of serum galactomannan in mixed ICU patients: a

retrospective observational study Anaesthesiology Intensive Therapy 2014, vol. 46, no 3, 145–154

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9. Bailey RJ, Woolf IL, Cullens H et al.: Metabolic inhibition of polymorphonuclear leucocytes in fulminant hepatic failure. Lancet 1976; 1: 1162–1163.

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12. Woods G, Miceli MH, Grazziutti ML et al.: Serum Aspergillus galactomannan antigen values strongly correlate with outcome of invasive aspergillosis: a study of 56 patients with haematologic cancer. Cancer 2007; 110: 830–834.

13. Koo S, Bryar JM, Baden LR et al.: Prognostic features of galactomannan antigenemia in galactomannan-positive invasive aspergillosis. J Clin Microbiol 2010; 48: 1255–1260.

14. Lehrnbecher T, Phillips R, Alexander S, et al. Guideline for the Management of Fever and Neutropenia in Children With Cancer and/or Undergoing Hematopoietic Stem-Cell Transplantation. Journal of Clinical Oncology. 2012 epub ahead of print. This manuscript is the first pediatric fever and neutropenia guideline. It summarizes the impact of both galactomannan and beta glucan testing in children.