重症患者气道分泌物曲霉培养阳性的临床意义

The clinical significance of Aspergillus isolation from airway samples in critically iH patients

目的分析重症患者气道分泌物曲霉培养阳性的危险因素及其临床意义。方法收集2007年1—12月在北京协和医院ICU住院的、怀疑肺部真菌感染的患者，每周进行3次气道分泌物培养，根据培养结果分为真菌培养阴性、念珠菌培养阳性和曲霉培养阳性三组，分析与曲霉阳性相关的危险因素，同时针对曲霉培养阳性的患者，按照诊断标准划分为确诊、临床诊断和定植，比较感染组（确诊和临床诊断）与定植组的临床特征，分析由定植到感染的危险因素。采用SPSS12．0软件处理数据，计量资料用面±s表示，采用Students’t检验（正态分布）或秩和检验（非正态分布）。计数资料采用X2检验。多组计量资料比较采用单因素方差分析。采用logistic回归进行多因素分析。结果160例中，男82例，女78例，年龄28～81岁，平均（64．5±17．2）岁。气道分泌物曲霉培养阳性45例，念珠菌阳性63例，真菌培养阴性52例，三组患者的病死率依次为48．9％（22／45）、23．8％（15／63）和7．7％（4／52），曲霉阳性者病死率高于念珠菌阳性者及真菌培养阴性者。曲霉阳性的45例中，28例为感染（2例确诊，26例临床诊断），曲霉培养阳性预测感染的比例为62％（28／45）。多元回归分析结果显示，自身免疫性疾病（OR=3．3，95％CI为1．7—12．2，χ^2=4．82，P〈0．01）、肝功能不全（OR=8．1，95％CI为1．7—15．2，χ^2=19．2，P〈0．01）、糖皮质激素治疗（OR=4．6，95％CI为2．6～13．7，χ^2=8．92，P〈0．01）、肾脏替代治疗（OR=5．1，95％CI为2．6～11．5，χ^2=11．4，P〈0．01）是曲霉分离阳性的独立危险因素。曲霉感染组较定植组的急性生理与慢性健康Ⅱ评分（APACHEⅡ；25±6和14±8，t=2．75，P〈0．01）及感染性休克的发生率高（57％和27％，χ^2=3．56，P〈0．01），抗生素使用时间长（15．9d和9．2d，t=2．49，P〈0．01）。结论重症患者气道分泌物曲霉培养阳性者较阴性者病死率高。自身免疫性疾病、肝功能不全、应用糖皮质激素及肾脏替代治疗与气道分泌物曲霉分离阳性有关。当患者合并严重疾病状态时，气道分泌物曲霉阳性对预测感染有较高的价值。

Objective To analyze the risk factors and clinical significance of Aspergillus isolaton from airway samples of critically ill patients. Methods The study was conducted in an ICU between January 2007 and December 2007. The data of patients receiving mechanical ventilation with suspected invasive pulmonary fungal infection were analyzed. Tracheal aspirates were collected and cultured 3 times weekly. The cases were classified into groups of Aspergillus spp, Candlda spp, and non-fungus spp according to the microbiological results. Isolation of Aspergillus spp. was subgrouped to proved-IPA （invasive pulmonary aspergillosis） , probable-IPA or colonization. The risk factors for airway isolation of Aspergillus and infection were assessed. Statistical analysis was performed using the Statistical Package for the Social Sciences （SPSS） for Windows （version 12. 0） and quantitative variables were expressed as mean ± standard deviation. The Student＇ s t-test or the Mann-Whitney U-test was used for the comparison of categorical and normally distributed and nonnormally distributed variables, respectively. The X2 test or the Fisher＇ s exact test was used in the comparison of categorical variables. Logistic regression analysis was conducted to evaluate risk factors for the isolation of Aspergillus spp. Results The study population included 160 patients （ 82 men） with a mean age of （64. 5 ± 17. 2 ） years. Aspergillus spp was isolated in 45, Candida spp in 63, and nonfungus spp in 52. The ICU mortality in the 3 groups was 48.9% （22/45 cases） ,23.8% （15/63 cases）, 7.7% （4/52 cases）, respectively. The ICU mortality in patients with Aspergillus spp. isolation was higher than those with Candida spp and non-fungus spp. In 28 patients isolation of Aspergillus spp. was interpreted as invasive aspergillosis（2 patients were proven, 26 patients were probable）. The predictive value of isolating Aspergillus from airway samples was 62% （28/45 cases）. On multivariate analysis, the following factors were independently associated with AspergiUus spp. isolation： connective tissue diseases （ OR 3.3, 95% CI 1.7 - 12. 2,χ^2=4. 82,P 〈 0.01）, hepatic dysfunction （OR 8. 1, 95% CI 1.7 - 15.2, χ^2 = 19. 2, P 〈 0.01）, corticosteroid use （ OR 4. 6, 95% CI 2. 6 - 13.7, χ^2 = 8.92, P 〈 0. 01 ） and continuous renal replacement therapy （CRRT） （ OR 5.1, 95% CI 2. 6 - 11.5, χ^2 = 11.4,P 〈0. 01 ）. Higher APACHE Ⅱ score（25 ± 6, 14 ±8, t =2. 75, P 〈 0. 01） , septic shock （57%, 27%, χ^2= 3.56, P 〈 0. 01 ）, and prolonged use of broad-spectrum antibiotics （ 15.9 d, 9. 2 d, t = 2. 49, P 〈 0. 01 ） were siguificantly associated with Aspergillus infection as compared to colonization. Conclusion Critically ill patients with Aspergillus from airway samples had a higher mortality. Connective tissue diseases, hepatic dysfunction, corticosteroid use and CRRT were significantly associated with Aspergillus spp. isolation in critically ill patients. In severely ill patients, the isolation of Aspergillus is highly indicative of infection rather than colonization.