Objective: To investigate the incidence, clinical and microbiological features of febrile, and risk factors during neutropenia periods in patients with hematological diseases.
Methods: From October 20, 2014 to March 20, 2015, consecutive patients who had hematological diseases and developed neutropenia during hospitalization were enrolled in the prospective, multicenter and observational study.
Results: A total of 784 episodes of febrile occurred in 1 139 neutropenic patients with hematological diseases. The cumulative incidence of febrile was 81.9% at 21 days after neutropenia. Multivariate analysis suggested that central venous catheterization (P<0.001, HR=3.407, 95% CI 2.276-4.496), gastrointestinal mucositis (P<0.001, HR=10.548, 95% CI 3.245-28.576), previous exposure to broad-spectrum antibiotics within 90 days (P<0.001, HR=3.582, 95% CI 2.387-5.770) and duration of neutropenia >7 days (P<0.001,HR=4.194, 95% CI 2.572-5.618) were correlated with higher incidence of febrile during neutropenia. With the increase of the risk factors, the incidence of febrile increased gradually (35.4%, 69.2%, 86.1%, 95.6%, P<0.001). Of 784 febrile cases, 253 (32.3%) were unknown origin, 429 (54.7% )of clinical documented infections and 102(13.0%) of microbiological documented infections. The most common sites of infection were pulmonary (49.5%), upper respiratory (16.0%), crissum (9.8%), blood stream (7.7%). The most common pathogens were gram-negative bacteria (44.54%), followed by gram-positive bacteria (37.99% ) and fungi (17.47% ). There was no significant difference in mortality rates between cases with febrile and cases without febrile (9.2% vs 4.8%, P=0.099). Multivariate analysis also suggested that >40 years old (P=0.047, HR=5.000, 95% CI 0.853-28.013), hemodynamic instability (P=0.001, HR=13.185, 95% CI 2.983-54.915), prior colonization or infection by resistant pathogens (P=0.005, HR=28.734, 95% CI 2.921-313.744), blood stream infection (P=0.038, HR=9.715, 95% CI 1.110-81.969) and pulmonary infection (P=0.031, HR=25.905, 95% CI 1.381-507.006) were correlated with higher mortality rate in cases with febrile.
Conclusions: Febrile was the common complication during neutropenia periods in patients with hematological disease. There was different distribution of organisms in different sites of infection. Moreove, the duration of neutropenia >7 days, central venous catheterization, gastrointestinal mucositis and previous exposure to broad-spectrum antibiotics within 90 days were the risk factors for the higher incidence of febrile.
目的: 了解中国血液病患者中性粒细胞缺乏（粒缺）伴发热的发生率、临床和微生物学特征及危险因素。
方法: 前瞻性研究2014年10月20日至2015年3月20日来自全国11家血液病中心发生粒缺伴发热的连续血液病患者发热情况及危险性因素。
结果: 1 139例患者共发生784例次粒缺伴发热，粒缺持续21 d时发热的累积发生率为81.9%。多因素分析显示中心静脉置管（P<0.001，HR= 3.407，95% CI 2.276~4.496）、胃肠道黏膜炎（P<0.001，HR=10.548, 95% CI 3.245~28.576）、既往90 d内暴露于广谱抗生素（P<0.001，HR=3.582，95% CI 2.387~5.770）和粒缺持续时间>7 d（P<0.001，HR= 4.194，95% CI 2.572~5.618）是粒缺伴发热的危险因素。无任何危险因素、具备1项、2项、3~4项危险因素患者发热的累计发生率依次增加（35.4%、69.2%、86.1%及95.6%，P<0.001）。784例次粒缺伴发热中，不明原因发热253例次（32.3%），临床证实的感染429例次（54.7%），微生物学证实的感染102例次（13.0%）。最常见的感染部位依次为肺（388例次，49.5%）、上呼吸道（159例次，16.0%）、肛周组织（77例次，9.8%）、血流（60例次，7.7%）。最常见的病原菌为革兰阴性菌（44.54%），其次为革兰阳性菌（37.99%）和真菌（17.47%）。发热与未发热患者相比，两组之间总体病死率差异无统计学意义（9.2%对4.8%，P=0.099）。多因素分析显示年龄>40岁（P=0.047，HR=5.000，95% CI 0.853~28.013）、血流动力学不稳（P=0.001，HR=13.185, 95% CI 2.983~54.915）、既往耐药菌的定植或感染（P=0.005，HR=28.734，95% CI 2.921~313.744）、血流感染（P=0.038，HR=9.715, 95% CI 1.110~81.969）和肺部感染（P=0.031，HR=25.905, 95% CI 1.381~507.006）是与总体死亡相关的危险因素。
结论: 发热是血液病患者粒缺期常见的合并症，不同部位的感染有不同的致病菌谱。粒缺持续时间>7 d、中心静脉置管、胃肠道黏膜炎和既往90 d内暴露于广谱抗生素是粒缺伴发热发生的危险因素。