Epidemiological and prognostic analysis of bloodstream infections in patients with different types of acute leukemia——a nine-year multicenter retrospective study of 947 patients
-
摘要: 目的 分析不同类型急性白血病(AL)患者合并血流感染的流行病学、临床特征及预后情况，为临床精准诊疗改善预后提供理论依据。方法 收集2010年1月—2018年12月湖南省3家大型医院血液科947例成人AL合并血流感染患者的临床资料，其中急性髓系白血病(AML)613例、急性淋巴细胞白血病(ALL)334例，根据不同AL分类对流行病学、临床特征及预后进行分析。结果 2种类型AL患者发生血流感染的病原流行病学分布及预后相似。在病原菌分布方面，G－菌为2种类型AL合并血流感染患者的主要致病菌，分别占66.6% vs 75.1%，其次为G+菌(25.9% vs 16.5%)和真菌(7.5% vs 8.4%)。耐药菌分布方面，2组均有较高的多重耐药菌占比(61.7% vs 59.9%)，2组碳青霉烯耐药G－菌占比类似(9.1% vs 7.7%)；临床特征方面，AML组患者年龄≥55岁(17.8% vs 11.1%，P=0.006)、查尔森指数>3(21.4% vs 15.9%，P=0.041)、疾病状态缓解(36.9% vs 21.3%，P＜0.001)显著高于ALL组。ALL患者倾向于更差的实验室指标，如Hb＜55.0 g/dL、ALB＜30.0 g/L、TBil>34.2 μmol/L的发生率更高(P＜0.05)。2组AL合并血流感染患者均出现较高的30 d死亡率(18.8% vs 17.7%，P=0.677)。预后因素方面，2组患者呈现不一样的特点，除呼吸衰竭、Pitt评分>3分、使用敏感抗生素共同独立预后危险因素外，AML合并血流感染患者的预后独立危险因素还包括疾病状态未缓解(P＜0.001)、使用血管活性药物(P＜0.001)，而ALL合并血流感染患者预后独立危险因素为年龄≥60岁(P=0.006)、胆红素升高≥2倍(P＜0.001)，中性粒细胞缺乏情况并非2组患者合并血流感染的预后欠佳危险因素。结论 研究结果表明AML与ALL合并血流感染患者的病原菌、耐药分布及预后相似，但预后因素方面，针对不同类型AL合并血流感染患者，除尽早使用敏感抗生素、改善呼吸功能外，AML应注意改善疾病状态、撤离血管活性药物，而对于ALL合并血流感染患者，加强脏器功能支持等治疗有助于改善预后。Abstract: Objective To analyze the epidemiology, clinical characteristics and prognosis of patients with different types of acute leukemia(AL) combined with bloodstream infection, in order to provide a theoretical basis for accurate clinical treatment and prognosis improvement.Methods The clinical data of 947 adult patients with AL combined with bloodstream infection in the hematology departments of three large hospitals in Hunan Province from January 2010 to December 2018 were collected, including 613 cases of acute myeloid leukemia(AML) and 334 cases of acute lymphoblastic leukemia(ALL), and the epidemiology, clinical characteristics and prognosis were analyzed according to different AL classifications.Results The pathogenic epidemiological distribution and prognosis of bloodstream infection in patients with both types of AL were similar. In terms of pathogenic distribution, G－bacteria were the main causative organisms in patients with both types of AL co-infections, accounting for 66.6% vs 75.1%, followed by G+ bacteria(25.9% vs 16.5%) and fungi(7.5% vs 8.4%), respectively. The distribution of resistant organisms, both AML and ALL had a high proportion of MDR organisms(61.7% vs 59.9%) and a similar proportion of carbapenem-resistant G－bacteria(9.1% vs 7.7%); with regard to clinical characteristics, the proportions of patients in the AML group with ≥55 years old(17.8% vs 11.1%, P=0.006), Charlson index>3(21.4% vs 15.9%, P=0.041), and remission of disease status(36.9% vs 21.3%, P < 0.001) were significantly higher than those in the ALL group. Patients with ALL tended to have a higher incidence of worse laboratory indicators, such as Hb < 55.0 g/dL, ALB < 30.0 g/L, and TBil>34.2 μmol/L(P < 0.05). Patients with AL bloodstream infection in both groups showed higher 30-day mortality(18.8% vs 17.7%, P=0.677). Regarding prognostic factors, the two groups presented different characteristics, in addition to the common independent prognostic risk factors for respiratory failure, Pitt score>3, and use of sensitive antibiotics, independent prognostic risk factors for patients with AML bloodstream infection included unremission disease status(P < 0.001) and use of vasoactive agents(P < 0.001), while independent prognostic risk factors for patients with ALL bloodstream infection were age ≥60 years(P=0.006), total bilirubin elevation ≥2-fold(P < 0.001), and neutropenia was not a risk factor for poor prognosis in patients with combined bloodstream infection in both groups.Conclusion It shows that the pathogenic bacteria, drug resistance distribution and prognosis of patients with AML and ALL complicated with bloodstream infection are similar, but in terms of prognostic factors, for patients with different types of AL bloodstream infection, in addition to early use of sensitive antibiotics and improvement of respiratory function, attention should be paid to improving disease status and evacuating vasoactive agents in AML, and strengthening organ function support for patients with all bloodstream infection will help improve prognosis.
-
-
表 1 AML与ALL血流感染患者的临床资料情况
例(%) 临床资料 AML (n=613) ALL (n=334) P 一般情况 年龄≥60岁 109(17.8) 37(11.1) 0.006 男性 317(51.7) 183(54.8) 0.365 疾病状态 缓解 226(36.9) 71(21.3) ＜0.001 未缓解 387(63.1) 263(78.7) ＜0.001 初治 149(24.3) 119(35.6) ＜0.001 合并症 糖尿病 43(7.0) 20(6.0) 0.545 心血管疾病 42(6.9) 19(5.7) 0.486 危险因素 查尔森指数>3 131(21.4) 53(15.9) 0.041 Pitt菌血症评分>3分 141(23.0) 92(27.5) 0.121 中性粒细胞缺乏 573(93.5) 321(96.1) 0.092 严重中性粒细胞缺乏 529(86.3) 304(91.0) 0.033 长期中性粒细胞缺乏 204(33.3) 126(37.7) 0.170 既往1个月化疗 560(91.4) 319(95.5) 0.018 免疫抑制剂 255(41.6) 176(52.7) 0.001 CVC管置入 231(37.7) 138(41.3) 0.273 医院感染 547(89.2) 316(94.6) 0.005 脏器功能 使用血管活性药物 112(18.3) 76(22.8) 0.098 急性呼吸衰竭 105(17.1) 53(15.9) 0.619 急性肾功能不全 16(2.6) 15(4.5) 0.120 抗生素治疗 既往抗生素暴露 355(57.9) 206(61.7) 0.260 72 h-IIAT 404(65.9) 230(68.9) 0.355 使用敏感抗生素 508(82.9) 290(86.8) 0.110 实验室指标 Hb＜55 g/dL 235(38.3) 160(47.9) 0.004 PLT＜10×109/L 383(62.5) 211(63.2) 0.833 ALB＜30 g/L 300(48.9) 197(59.0) 0.003 AST>120 U/L 45(7.3) 34(10.2) 0.131 TBil>34.2 μmol/L 64(10.4) 51(15.3) 0.030 PT>14 s 146(23.8) 94(28.1) 0.144 预后 7 d死亡率 78(12.7) 34(10.2) 0.247 30 d死亡率 115(18.8) 59(17.7) 0.677 
下载: 导出CSV
表 2 AML与ALL血流感染患者病原菌分布
例(%) 病原菌 AML (n=613) ALL (n=334) G-菌 408(66.6) 251(75.1) 肠杆菌 308(75.5) 200(79.7) 大肠杆菌 175(42.9) 112(44.6) 肺炎克雷伯菌 89(21.8) 62(24.7) 阴沟肠杆菌 12(2.9) 13(5.2) 其他肠杆菌 32(7.8) 13(5.2) 非发酵菌 92(22.5) 44(17.5) 铜绿假单孢菌 56(13.7) 30(12.0) 嗜麦芽窄食单胞菌 8(2.0) 6(2.4) 鲍曼不动杆菌 17(4.2) 3(1.2) 其他非发酵菌 11(2.7) 5(2.0) 其他G-菌 8(2.0) 7(2.8) G+菌 159(25.9) 55(16.5) 凝固酶阴性葡萄球菌 79(49.7) 29(52.7) 金黄色葡萄球菌 23(14.5) 7(12.7) 链球菌属 34(21.4) 10(18.2) 肠球菌属 13(8.2) 5(9.1) 其他G+菌 10(6.3) 4(7.3) 真菌 46(7.5) 28(8.4) 念珠菌属 46(100.0) 27(96.4) 其他真菌 0 1(3.6)
下载: 导出CSV
表 3 AML患者血流感染30 d死亡预后分析
影响因素 OR(95%CI) P 疾病状态未缓解 11.988(4.376~32.845) ＜0.001 Pitt评分>3分 2.711(1.298~5.662) 0.008 使用血管活性药物 7.134(3.339~15.280) ＜0.001 出现呼吸衰竭 3.791(2.574~5.583) ＜0.001 未使用敏感药物 2.435(1.192~4.988) 0.047
下载: 导出CSV
表 4 ALL患者血流感染30 d死亡预后分析
影响因素 OR(95%CI) P 年龄≥60岁 6.956(1.726~28.028) 0.006 Pitt评分>3分 4.374(1.772~10.795) 0.001 胆红素升高≥2倍 5.917(2.239~15.638) ＜0.001 出现呼吸衰竭 3.015(1.916~4.742) ＜0.001 未使用敏感药物 3.246(2.091~5.664) 0.006
下载: 导出CSV
-
[1] Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia[J]. Lancet, 2018, 392(10147): 593-606. doi: 10.1016/S0140-6736(18)31041-9
[2] de Haas V, Ismaila N, Advani A, et al. Initial Diagnostic Work-Up of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists and American Society of Hematology Guideline[J]. J Clin Oncol, 2019, 37(3): 239-253. doi: 10.1200/JCO.18.01468
[3] Tang Y, Cheng Q, Yang Q, et al. Prognostic factors and scoring model of hematological malignancies patients with bloodstream infections[J]. Infection, 2018, 46(4): 513-521. doi: 10.1007/s15010-018-1151-3
[4] Silva R, de Mendonça R, Dos Santos Aguiar S, et al. Induction therapy for acute lymphoblastic leukemia: incidence and risk factors for bloodstream infections[J]. Support Care Cancer, 2022, 30(1): 695-702. doi: 10.1007/s00520-021-06471-8
[5] 王二华, 张畅, 唐亦舒, 等. 急性白血病患者革兰氏阴性菌血流感染的药敏分析及预后[J]. 中南大学学报(医学版), 2020, 45(9): 1068-1073. https://www.cnki.com.cn/Article/CJFDTOTAL-HNYD202009011.htm
[6] 张畅, 唐亦舒, 成倩, 等. 急性白血病患者革兰阳性菌血流感染的病原学及临床特征分析[J]. 中国抗生素杂志, 2020, 45(11): 1176-1181. doi: 10.3969/j.issn.1001-8689.2020.11.014
[7] Di Domenico EG, Marchesi F, Cavallo I, et al. The Impact of Bacterial Biofilms on End-Organ Disease and Mortality in Patients with Hematologic Malignancies Developing a Bloodstream Infection[J]. Microbiol Spectr, 2021, 9(1): e55021.
[8] Amanati A, Sajedianfard S, Khajeh S, et al. Bloodstream infections in adult patients with malignancy, epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance[J]. BMC Infect Dis, 2021, 21(1): 636. doi: 10.1186/s12879-021-06243-z
[9] 中华医学会血液学分会, 中国医师协会血液科医师分会. 中国中性粒细胞缺乏伴发热患者抗菌药物临床应用指南(2020年版)[J]. 中华血液学杂志, 2020, 41(12): 969-978. doi: 10.3760/cma.j.issn.0253-2727.2020.12.001
[10] 谭家乐, 杨华强, 李红, 等. 急性白血病患者合并血流感染的临床特点分析[J]. 中国医学工程, 2019, 27(12): 14-18. https://www.cnki.com.cn/Article/CJFDTOTAL-YCGC201912004.htm
[11] 韦杰敏, 赖小璇, 章忠明, 等. 急性白血病患者细菌性血流感染临床和病原学分析[J]. 中国实验血液学杂志, 2019, 27(6): 1774-1778. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY201906015.htm
[12] 刘育欣, 王婷婷, 肖玉玲, 等. 不同临床分类的急性白血病患者病原学数据分析[J]. 现代预防医学, 2016, 43(10): 1903-1906. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF201610053.htm
[13] Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: twentysecond informational supplement. CLSI document M100-S22[S]. Wayne, PA: C1251, 2012.
[14] Tang Y, Xu C, Xiao H, et al. Gram-Negative Bacteria Bloodstream Infections in Patients with Hematological Malignancies-The Impact of Pathogen Type and Patterns of Antibiotic Resistance: A Retrospective Cohort Study[J]. Infect Drug Resist, 2021, 14: 3115-3124. doi: 10.2147/IDR.S322812
[15] 魏同, 毛夏丽, 周琪, 等. 急性白血病粒细胞缺乏症患者医院感染的临床特征及影响因素研究[J]. 临床血液学杂志, 2020, 33(9): 634-639. http://lcxz.cbpt.cnki.net/WKC/WebPublication/paperDigest.aspx?paperID=da2b3cbc-51f3-41a0-9d49-6c698ad387b9
[16] 刘德琰, 熊敏, 张建平, 等. 757例异基因造血干细胞移植患者植活前血流感染的发生率和危险因素分析[J]. 临床血液学杂志, 2021, 34(1): 24-30. http://lcxz.cbpt.cnki.net/WKC/WebPublication/paperDigest.aspx?paperID=4b025fb7-bf8a-4801-8ba8-a92397b2d5b4
[17] Kuo FC, Wang SM, Shen CF, et al. Bloodstream infections in pediatric patients with acute leukemia: Emphasis on gram-negative bacteria infections[J]. J Microbiol Immunol Infect, 2017, 50(4): 507-513.
[18] Zhang Y, Wang Q, Yin Y, et al. Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network[J]. Antimicrob Agents Chemother, 2018, 62(2): e01882-17.
[19] Mattei D, Baretta V, Mazzariol A, et al. Characteristics and Outcomes of Bloodstream Infections in a Tertiary-Care Pediatric Hematology-Oncology Unit: A 10-Year Study[J]. J Clin Med, 2022, 11(3): 880.
[20] 安淑娟, 刘蓓. 急性白血病合并血流感染的病原学及预后分析[J]. 检验医学与临床, 2022, 19(17): 2336-2340. https://www.cnki.com.cn/Article/CJFDTOTAL-JYYL202217008.htm
[21] 金洁, 周一乐. 成人急性髓细胞白血病的诊断与治疗进展[J]. 临床血液学杂志, 2022, 35(5): 309-311, 317. http://lcxz.cbpt.cnki.net/WKC/WebPublication/paperDigest.aspx?paperID=a876f529-e2e0-49e3-b186-93c89d0104ea
[22] 何静, 胡俊斌. 成人急性淋巴细胞白血病诊断和治疗之浅见[J]. 临床血液学杂志, 2022, 35(3): 221-224. http://lcxz.cbpt.cnki.net/WKC/WebPublication/paperDigest.aspx?paperID=731c4a18-757b-4f5b-8b07-405cca18b4f6
[23] 王聪, 刘妍, 崔北辰, 等. APACHEⅡ和PITT评分对急诊老年社区发病的血流感染预后的预测价值[J]. 中国急救医学, 2021, 41(10): 893-897. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJJY202110012.htm
[24] 成栋, 张泓, 丁振兴, 等. ICU内革兰阴性菌血流感染预后危险因素分析[J]. 临床急诊杂志, 2022, 23(4): 255-260. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZLC202204007.htm
-