儿童急性白血病化疗后合并真菌血流感染的临床特征及预后分析

翁开枝; 吴椿萍; 庄树铨; 黄淑贤; 王晓芳; 郑湧智

doi:10.7499/j.issn.1008-8830.2406021

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中国当代儿科杂志 ›› 2024, Vol. 26 ›› Issue (10) : 1086-1092. DOI: 10.7499/j.issn.1008-8830.2406021

论著·临床研究

儿童急性白血病化疗后合并真菌血流感染的临床特征及预后分析

翁开枝¹, 吴椿萍², 庄树铨³, 黄淑贤¹, 王晓芳³, 郑湧智²

作者信息 +

Clinical features and prognosis of children with fungal bloodstream infection following chemotherapy for acute leukemia

WENG Kai-Zhi, WU Chun-Ping, ZHUANG Shu-Quan, HUANG Shu-Xian, WANG Xiao-Fang, ZHENG Yong-Zhi

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摘要

目的探讨儿童急性白血病（acute leukemia, AL）化疗后合并真菌血流感染（bloodstream infection， BSI）的临床特征及预后。方法回顾性选择2015年1月—2023年12月在福建3家医院行AL化疗后合并真菌BSI的23例患儿作为研究对象，对其临床特征及预后进行分析。结果所有AL患儿化疗后合并真菌BSI的发生率为1.38%（23/1 668）。在发生真菌BSI时，87%（20/23）患儿中性粒细胞缺乏已持续超过1周；临床上均有发热表现，22%（5/23）伴脓毒性休克表现。23例（100%）均有C反应蛋白及降钙素原水平明显升高。外周血培养共检出23株真菌，其中以热带念珠菌（52%，12/23）最为常见。卡泊芬净或米卡芬净联合两性霉素B脂质体治疗有效率较高（75%，12/16），抗真菌疗程中位数为3.0个月。总体病死率为35%（8/23），归因死亡率为22%（5/23）。结论儿童AL化疗后合并真菌BSI多发生于持续中性粒细胞缺乏，临床表现缺乏特异性，病原菌以热带念珠菌最为常见，抗真菌疗程长，病死率高。

Abstract

Objective To investigate the clinical features and prognosis of children with fungal bloodstream infection (BSI) following chemotherapy for acute leukemia (AL). Methods A retrospective analysis was performed on 23 children with fungal BSI following chemotherapy for AL in three hospitals in Fujian Province, China, from January 2015 to December 2023. Their clinical features and prognosis were analyzed. Results Among all children following chemotherapy for AL, the incidence rate of fungal BSI was 1.38% (23/1 668). At the time of fungal BSI, 87% (20/23) of the children had neutrophil deficiency for more than one week, and all the children presented with fever, while 22% (5/23) of them experienced septic shock. All 23 children exhibited significant increases in C-reactive protein and procalcitonin levels. A total of 23 fungal isolates were detected in peripheral blood cultures, with Candida tropicalis being the most common isolate (52%, 12/23). Caspofungin or micafungin combined with liposomal amphotericin B had a relatively high response rate (75%, 12/16), and the median duration of antifungal therapy was 3.0 months. The overall mortality rate in the patients with fungal BSI was 35% (8/23), and the attributable death rate was 22% (5/23). Conclusions Fungal BSI following chemotherapy in children with AL often occurs in children with persistent neutrophil deficiency and lacks specific clinical manifestations. The children with fungal BSI following chemotherapy for AL experience a prolonged course of antifungal therapy and have a high mortality rate, with Candida tropicalis being the most common pathogen.

导出引用

翁开枝, 吴椿萍, 庄树铨, 黄淑贤, 王晓芳, 郑湧智. 儿童急性白血病化疗后合并真菌血流感染的临床特征及预后分析[J]. 中国当代儿科杂志. 2024, 26(10): 1086-1092 https://doi.org/10.7499/j.issn.1008-8830.2406021

WENG Kai-Zhi, WU Chun-Ping, ZHUANG Shu-Quan, HUANG Shu-Xian, WANG Xiao-Fang, ZHENG Yong-Zhi. Clinical features and prognosis of children with fungal bloodstream infection following chemotherapy for acute leukemia[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(10): 1086-1092 https://doi.org/10.7499/j.issn.1008-8830.2406021

参考文献

1 Inaba H, Mullighan CG. Pediatric acute lymphoblastic leukemia[J]. Haematologica, 2020, 105(11): 2524-2539. PMID: 33054110. PMCID: PMC7604619. DOI: 10.3324/haematol.2020.247031.
2 Rubnitz JE, Kaspers GJL. How I treat pediatric acute myeloid leukemia[J]. Blood, 2021, 138(12): 1009-1018. PMID: 34115839. DOI: 10.1182/blood.2021011694.
3 Otto WR, Green AM. Fungal infections in children with haematologic malignancies and stem cell transplant recipients[J]. Br J Haematol, 2020, 189(4): 607-624. PMID: 32159231. PMCID: PMC7231650. DOI: 10.1111/bjh.16452.
4 鄢露, 郑敏翠, 鞠秀丽, 等. 儿童急性淋巴细胞白血病合并热带念珠菌血症14例分析[J]. 中华儿科杂志, 2020, 58(10): 813-817. PMID: 32987460. DOI: 10.3760/cma.j.cn112140-20200323-00298.
5 姜锦, 姚佳峰, 李楠. 儿童急性白血病合并真菌血症相关危险因素的病例对照研究[J]. 中国循证儿科杂志, 2016, 11(2): 118-121. DOI: 10.3969/j.issn.1673-5501.2016.02.007.
6 Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J]. Blood, 2016, 127(20): 2391-2405. PMID: 27069254. DOI: 10.1182/blood-2016-03-643544.
7 Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms[J]. Blood, 2016, 127(20): 2375-2390. PMID: 26980727. PMCID: PMC4874220. DOI: 10.1182/blood-2016-01-643569.
8 Cui L, Li ZG, Chai YH, et al. Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: the first nation-wide prospective multicenter study in China[J]. Am J Hematol, 2018, 93(7): 913-920. PMID: 29675840. DOI: 10.1002/ajh.25124.
9 Yang W, Cai J, Shen S, et al. Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial[J]. Lancet Oncol, 2021, 22(9): 1322-1332. PMID: 34329606. PMCID: PMC8416799. DOI: 10.1016/S1470-2045(21)00328-4.
10 Zheng Y, Pan L, Li J, et al. Prognostic significance of multiparametric flow cytometry minimal residual disease at two time points after induction in pediatric acute myeloid leukemia[J]. BMC Cancer, 2024, 24(1): 46. PMID: 38195455. PMCID: PMC10775489. DOI: 10.1186/s12885-023-11784-4.
11 中华人民共和国卫生部. 医院感染诊断标准（试行）[J]. 中华医学杂志, 2001, 81(5): 314-320. DOI: 10.3760/j:issn:0376-2491.2001.05.027.
12 中华医学会儿科学分会血液学组, 《中华儿科杂志》编辑委员会. 儿童血液系统疾病及恶性肿瘤侵袭性真菌病诊疗建议[J]. 中华儿科杂志, 2014, 52(6): 426-429. PMID: 25190161. DOI: 10.3760/cma.j.issn.0578-1310.2014.06.006.
13 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（2016年版）[J]. 中华血液学杂志, 2016, 37(5): 353-359. PMID: 27210867. PMCID: PMC7348317. DOI: 10.3760/cma.j.issn.0253-2727.2016.05.001.
14 Auberger J, Lass-Fl?rl C, Ulmer H, et al. Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies[J]. Int J Hematol, 2008, 88(5): 508-515. PMID: 18982251. DOI: 10.1007/s12185-008-0184-2.
15 李琰冰, 徐英春, 张丽. 不容忽视的儿童侵袭性真菌感染[J]. 中华实用儿科临床杂志, 2024, 39(1): 2-6. DOI: 10.3760/cma.j.cn101070-20230621-00507.
16 Cornely OA, Gachot B, Akan H, et al. Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031)[J]. Clin Infect Dis, 2015, 61(3): 324-331. PMID: 25870323. DOI: 10.1093/cid/civ293.
17 廖雄宇, 邱坤银, 吴若豪, 等. 儿童血液病合并侵袭性真菌病164例临床分析[J]. 中国实验血液学杂志, 2019, 27(5): 1672-1677. DOI: 10.19746/j.cnki.issn1009-2137.2019.05.048.
18 Pana ZD, Roilides E, Warris A, et al. Epidemiology of invasive fungal disease in children[J]. J Pediatric Infect Dis Soc, 2017, 6(suppl_1): S3-S11. PMID: 28927200. PMCID: PMC5907880. DOI: 10.1093/jpids/pix046.
19 Sahbudak Bal Z, Yilmaz Karapinar D, Karadas N, et al. Proven and probable invasive fungal infections in children with acute lymphoblastic leukaemia: results from an university hospital, 2005-2013[J]. Mycoses, 2015, 58(4): 225-232. PMID: 25728069. DOI: 10.1111/myc.12303.
20 中华医学会儿科学分会, 中华儿科杂志编辑委员会. 儿童侵袭性肺部真菌感染临床实践专家共识（2022版）[J]. 中华儿科杂志, 2022, 60(4): 274-282. PMID: 35385930. DOI: 10.3760/cma.j.cn112140-20220210-00112.
21 Lass-Fl?rl C, Kanj SS, Govender NP, et al. Invasive candidiasis[J]. Nat Rev Dis Primers, 2024, 10(1): 20. PMID: 38514673. DOI: 10.1038/s41572-024-00503-3.
22 Meng Y, Kang M, Li D, et al. Performance of a new Candida anti-mannan IgM and IgG assays in the diagnosis of candidemia[J]. Rev Inst Med Trop Sao Paulo, 2020, 62: e25. PMID: 32428065. PMCID: PMC7232961. DOI: 10.1590/S1678-9946202062025.
23 Zhang X, Zhang L, Li Y, et al. Clinical performance of metagenomic next-generation sequencing for diagnosis of invasive fungal disease after hematopoietic cell transplant[J]. Front Cell Infect Microbiol, 2024, 14: 1210857. PMID: 38590441. PMCID: PMC11000502. DOI: 10.3389/fcimb.2024.1210857.
24 Barakzai MD, Bozic D, Gupta S, et al. Fever at time of leukemia diagnosis in children: predictor of bloodstream infection or catheter removal?[J]. J Vasc Interv Radiol, 2024, 35(5): 751-758. PMID: 38342222. DOI: 10.1016/j.jvir.2024.02.003.
25 Chen CY, Huang SY, Tsay W, et al. Clinical characteristics of candidaemia in adults with haematological malignancy, and antimicrobial susceptibilities of the isolates at a medical centre in Taiwan, 2001-2010[J]. Int J Antimicrob Agents, 2012, 40(6): 533-538. PMID: 23006521. DOI: 10.1016/j.ijantimicag.2012.07.022.
26 Xiao M, Chen SC, Kong F, et al. Distribution and antifungal susceptibility of Candida species causing candidemia in China: an update from the CHIF-NET study[J]. J Infect Dis, 2020, 221(Suppl 2): S139-S147. PMID: 32176789. DOI: 10.1093/infdis/jiz573.
27 Khamrai A, Paul S, Rudramurthy SM, et al. Carbon substrates promotes stress resistance and drug tolerance in clinical isolates of Candida tropicalis[J]. Arch Microbiol, 2024, 206(6): 270. PMID: 38767668. DOI: 10.1007/s00203-024-04000-9.
28 Pristov KE, Ghannoum MA. Resistance of Candida to azoles and echinocandins worldwide[J]. Clin Microbiol Infect, 2019, 25(7): 792-798. PMID: 30965100. DOI: 10.1016/j.cmi.2019.03.028.
29 Wang Y, Fan X, Wang H, et al. Continual decline in azole susceptibility rates in Candida tropicalis over a 9-year period in China[J]. Front Microbiol, 2021, 12: 702839. PMID: 34305872. PMCID: PMC8299486. DOI: 10.3389/fmicb.2021.702839.
30 Lima R, Ribeiro FC, Colombo AL, et al. The emerging threat antifungal-resistant Candida tropicalis in humans, animals, and environment[J]. Front Fungal Biol, 2022, 3: 957021. PMID: 37746212. PMCID: PMC10512401. DOI: 10.3389/ffunb.2022.957021.
31 Cornely FB, Cornely OA, Salmanton-García J, et al. Attributable mortality of candidemia after introduction of echinocandins[J]. Mycoses, 2020, 63(12): 1373-1381. PMID: 32885534. DOI: 10.1111/myc.13177.
32 Mazi PB, Olsen MA, Stwalley D, et al. Attributable mortality of Candida bloodstream infections in the modern era: a propensity score analysis[J]. Clin Infect Dis, 2022, 75(6): 1031-1036. PMID: 34989802. PMCID: PMC10233239. DOI: 10.1093/cid/ciac004.