化疗后粒细胞缺乏住院患儿612例次发热原因分析

Causes of fever in hospitalized children with neutropenia after chemotherapy

目的探讨化疗后粒细胞缺乏（粒缺）状态下住院患儿的发热原因。方法2005年10月至2012年6月，共记录到中山大学附属第一医院儿科粒细胞缺乏（粒缺）时出现发热患儿的临床资料612例次，均为因肿瘤需要化疗或重型再生障碍性贫血需要强免疫抑制治疗的患儿。患儿住院期间在外周血中性粒细胞〈0．5×10VL时出现发热（腋温〉38℃），均进行表格化监测，记录其临床资料、实验室检查及影像检查结果，记录用药情况及换药理由。对表格定期汇总整理分析。结果7年间共记录到612例次粒缺发热，其中359、141、40和4例次分别存在1～4种可能的发热原因，原因不明的发热共68例次（68／612，11％）。单一原因发热中以上呼吸道感染最多（176／612，29％）。深部真菌感染共16例次（16／612，3％），其中4例次血流感染（2例次血流并其他器官感染）。血培养阳性共139例次，分离出146株病原菌，其中革兰阴性杆菌101株（肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌各占35、29、20株），阳性球菌41株（葡萄球菌、链球菌、肠球菌各占18、17、6株）。相比血培养阴性的患儿，败血症患儿体温更高（中位数39．6℃vs38．9℃），更常合并肛肠感染（30．9％VS．10．1％）和肺炎（10．8％vs．3．7％），也更常出现足背动脉脉搏减弱（25．9％vs．2．7％），P〈0．05。死亡10例（败血症7例），其中放弃治疗后死亡2例，另1例死于肿瘤。结论化疗后粒缺患儿发热原因较多，单一原因的发热以上呼吸道感染为主，但血流感染仍是重要原因之一。败血症病原茵以革兰阴性杆菌为主，经验用药需结合本地区菌谱及药敏情况。合并肛肠感染和肺炎时更需注意败血症的可能，并应严密监测患儿循环状态，及早防治感染性休克。

Objective To reveal the causes of fever in hospitalized children with neutropenia after chemotherapy. Meth- ods A data sheet recording detailed clinical data was filled out when the child had a fever. The data sheets were collect- ed and analysed regularly. Results A total of 612 neutropenic febrile episodes were recorded during the past 7 years. One, two, three and four possible causes were recognized in 359,141,40 and 4 episodes, respectively. Sixty-eight epi- sodes （ 11% ） were considered as fever of unknown origin. Upper respiratory tract infection accounted for most of febrile episoeds （ 176 cases, 29% ）. Sixteen patients （3%） were diagnosed with invasive fungal infection, of which 4 eases were bloodstream infection. Baeteremia accounted for 139 episodes with 146 isolated pathogens, including 101 gram-nega- tive bacilli （Klebsiella pneumoniae, Escherichia coli and seudomonas aeruginosa in 35,29 and 20 strains each） and 41 gram-positive cocci （Staphylococcus, Streptococcus, Enterococcus in 18,17 and 6 strains each）. Compared to negative blood culture patients, children with bacteremia showed higher body temperature （median 39.6 ℃ vs. 38.9 ℃ ）, more often associated with anorectal infection （30.9% vs. 10.1%） and pneumonia （ 10.8% vs. 3.7%）, and more often had poor dorsalis pedis artery pulse （25.9% vs. 2.7%）, P 〈 0.05. Ten patients died, of whom 7 died of bacteremia. Conclusions The etiology of fever in neutropenic children after chemotherapy is varied. Upper respiratory tract infection accounts for most of febrile episodes. Bloodstream infection is still one of the important cause. Most of the isolated pathogens are gram-negative bacilli, hence, antibiotics selection following the guideline of western country may not be advisable. More attention should be paid to those with anorectal infections and pneumonia for the possibility of bactermia and septicshock.