重症百日咳合并肺孢子菌肺炎患儿5例临床分析

doi:10.12372/jcp.2025.24e0226

摘要/Abstract

摘要：

目的提高对重症百日咳合并肺孢子菌肺炎(PCP)的认识，以期早期诊断，改善预后。方法回顾性分析2020年1月1日至2023年12月31日确诊的重症百日咳合并PCP患儿的临床资料及诊治经过。结果共纳入5例患儿，男1例、女4例，中位年龄3.0(2.5~10.0)个月，住院时间17.0(7.5~23.5)天，其中死亡3例。5例患儿均有呼吸暂停与低氧血症，3例合并急性呼吸窘迫综合征(ARDS)，3例同时合并肺动脉高压及百日咳脑病，5例白细胞计数(WBC)峰值中位数43.8(25.2~87.8)×10⁹/L，治疗后降至8.5(5.0~36.5)×10⁹/L，乳酸脱氢酶（LDH）中位数942.0(466.5~1 837.0)U/L，明显高于正常。5例患儿在确诊PCP前均给予阿奇霉素治疗，确诊PCP后均加用复方磺胺甲噁唑联合棘白菌素类药物，2例存活者于5日内给药。结论 PCP可发生在无免疫缺陷的重症百日咳患儿中，且重症百日咳合并PCP时死亡风险高，在儿童重症百日咳常规治疗效果不佳时，需警惕合并耶氏肺孢子菌( PJ )感染的可能，早期联合应用复方磺胺甲噁唑与棘白菌素类药物，有望改善预后。

关键词: 重症百日咳, 肺孢子菌肺炎, 耶氏肺孢子菌, 儿童

Abstract:

Objective To raise the awareness of Pneumocystis jirovecii pneumonia (PCP) in children complicated with severe pertussis, and to enable early diagnosis for improved prognosis. Methods The clinical data of children diagnosed with severe pertussis complicated by PCP from January 1, 2020 to December 31, 2023 were retrospectively analyzed. Results Five cases were enrolled, with one male and four females. The median age was 3.0(2.5-10.0) months, and the median hospital stay was 17.0(7.5-23.5) days, with three deaths recorded. All cases experienced apnea and hypoxemia, with 3 cases presented acute respiratory distress syndrome (ARDS), and 3 cases developed pulmonary hypertension and pertussis encephalopathy. The peak of leucocyte count were 43.8(25.2-87.8)×10⁹/L, which decreased to a post-treatment median of 8.5(5.0-36.5)×10⁹/L, and the median LDH was 942.0(466.5-1837.0) U/L. All 5 cases were treated with azithromycin before diagnosis of PCP, and co-trimoxazole combined with echinocandin were administered additionally for PCP, while 2 survivors were treated within 5 days. Conclusion PCP can occur in severe pertussis children without immunodeficiency, and there is a high risk of death when severe pertussis is complicated by PCP. When the routine treatment for severe pertussis in children has poor efficacy, it is necessary to be alert for Pneumocystis jirovecii infection. Early combined use of co-trimoxazole with echinocandin may improve prognosis.

Key words: severe pertussis, Pneumocystis jirovecii pneumonia, Pneumocystis jirovecii, child

郭芳, 康磊, 武晓圆, 贾艳红, 邸亚楠, 贾莉, 徐梅先. 重症百日咳合并肺孢子菌肺炎患儿5例临床分析[J]. 临床儿科杂志, 2025, 43(2): 99-104.

GUO Fang, KANG Lei, WU Xiaoyuan, JIA Yanhong, DI Yanan, JIA Li, XU Meixian. Analysis of children with severe pertussis complicated with Pneumocystis jirovecii pneumonia[J]. Journal of Clinical Pediatrics, 2025, 43(2): 99-104.

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参考文献 23

[1]	Lamrani Hanchi A, Guennouni M, Rachidi M, et al. Epidemiology of respiratory pathogens in children with severe acute respiratory infection and impact of the multiplex PCR film array respiratory panel: a 2-year study[J]. Int J Microbiol, 2021:2276261.
[2]	Yeung KHT, Duclos, P Nelson EAS, et al. An update of the global burden of pertussis in children younger than 5 years: a modelling study[J]. Lancet Infect Dis, 2017, 17(9): 974-980. doi: S1473-3099(17)30390-0 pmid: 28623146
[3]	张光莉, 田小银, 谷瑞雪, 等. 重庆地区重症百日咳患儿临床特点分析[J]. 临床儿科杂志, 2020, 38(2): 134-139.
	Zhang GL, Tian XY, Gu RX, et al. Analysis of clinical characteristics of children with severe pertussis in Chongqing[J]. Linchuang Erke Zazhi, 2020, 38(2): 134-139.
[4]	Kanj A, Samhouri B, Abdallah N, et al. Host factors and outcomes in hospitalizations for Pneumocystis jirovecii pneumonia in the United States[J]. Mayo Clin Proc, 2021, 96(2): 400-407.
[5]	杨颖, 高薇, 叶金艳, 等. 婴儿百日咳混合感染的病例对照研究[J]. 中华实用儿科临床杂志, 2022, 37(24): 1888-1894.
	Yang Y, Gao W, Ye JY, et al. A case-control study on mixed infection in infants with pertussis[J]. Zhonghua Shiyong Erke Linchuang Zazhi, 2022, 37(24): 1888-1894.
[6]	姚开虎, 李丽君. 重症百日咳的诊断及其死亡风险因素研究进展[J]. 中华实用儿科临床杂志, 2019, 34(22): 1681-1685.
	Yao KH, Li LJ. Advances in the diagnosis of severe pertussis and in the research of mortality risk factors from pertussis[J]. Zhonghua Shiyong Erke Linchuang Zazhi, 2019, 34(22): 1681-1685.
[7]	Donnelly JP, Chen SC, Kauffman CA, et al. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium[J]. Clin Infect Dis, 2020, 71(6): 1367-1376. doi: 10.1093/cid/ciz1008 pmid: 31802125
[8]	中华预防医学会, 中华预防医学会疫苗与免疫分会. 中国百日咳行动计划专家共识[J]. 中华实用儿科临床杂志, 2021, 36(11): 801-810.
	Chinese Preventive Medicine Association, Vaccine and Immunization Branch of the Chinese Preventive Medicine Association. Expert consensus on the China Pertussis Initiative[J]. Zhonghua Shiyong Erke Linchuang Zazhi, 2021, 36(11): 801-810.
[9]	Liu C, Yang L, Cheng YW, et al. Risk factors associated with death in infants<120 days old with severe pertussis: a case-control study[J]. BMC Infect Dis, 2020, 20(1): 852.
[10]	Azar MM, Slotkin R, Abi-Raad R, et al. Gomori methenamine silver stain on bronchoalveolar lavage fluid is poorly sensitive for diagnosis of Pneumocystis jirovecii pneumonia in HIV-negative immunocompromised patients and may lead to missed or delayed diagnoses[J]. Arch Pathol Lab Med, 2020. doi: 10.5858/arpa.2019-0394-OA.
[11]	Liu Y, Wang XN, Xu J, et al. Diagnostic value of metagenomic next-generation sequencing of lower respiratory tract specimen for the diagnosis of suspected Pneumocystis jirovecii pneumonia[J]. Ann Med, 2023, 55(1): 2232358.
[12]	Huang LP, Xu SY, Huang ZM, et al. Risk factors associated with Pneumocystis jirovecii pneumonia in non-HIV immunocompromised patients and co-pathogens analysis by metagenomic next-generation sequencing[J]. BMC Pulm Med, 2023, 23(1): 72.
[13]	Jiang J, Bai L, Yang W, et al. Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia in non-HIV-Infected patients: a retrospective study[J]. Infect Dis Ther, 2021, 10(3): 1733-1745. doi: 10.1007/s40121-021-00482-y pmid: 34244957
[14]	Belcher T, Dubois V, Rivera-Millot A, et al. Pathogenicity and virulence of Bordetella pertussis and its adaptation to its strictly human host[J]. Virulence, 2021, 12(1): 2608-2632. doi: 10.1080/21505594.2021.1980987 pmid: 34590541
[15]	Asai N, Motojima S, Ohkuni Y, et al. Pathophysiological mechanism of non-HIV Pneumocystis jirovecii pneumonia[J]. Respir Investig, 2022, 60(4): 522-530.
[16]	Mohamed YF, Manivannan K, Fernandez RC. Bordetella pertussis[J]. Trends Microbiol, 2023, 31(11):1192-1193. doi: 10.1016/j.tim.2023.03.012 pmid: 37024321
[17]	Zhang YQ, Ran ZH, Tian MM, et al. Commensal microbes affect host humoral immunity to Bordetella pertussis infection[J]. Infect Immun, 2019, 87(10): e00421-19.
[18]	吴小英, 甘川. 婴幼儿重症百日咳死亡相关因素分析[J]. 临床儿科杂志, 2020, 38(6): 432-437.
	Wu XY, Gan C. Analysis of risk factors of death in severe pertussis in infant[J]. Linchuang Erke Zazhi, 2020, 38(6): 432-437.
[19]	Wang CY, Zhang HM, Zhang YL, et al. Analysis of clinical characteristics of severe pertussis in infants and children: a retrospective study[J]. BMC Pediatr, 2021, 21: 65. doi: 10.1186/s12887-021-02507-4 pmid: 33546645
[20]	Charpentier E, Ménard S, Marques C, et al. Immune response in Pneumocystis infections according to the host immune system status[J]. J Fungi (Basel), 2021, 7(8): 625.
[21]	Cornelis R, Shulman Z. Bystander activation of tissue-resident memory CD4 T cells: Getting by with a little help from unfamiliar T-cell friends[J]. Eur J Immunol, 2023, 53(5): e2350413.
[22]	代艳, 李新叶, 唐慧荷, 等. 非HIV感染的免疫低下者肺孢子菌肺炎防治进展[J]. 中国临床新医学, 2021, 14(2): 134-138.
	Dai Y, Li XY, Tang HH, et al. Progress of the prevention and treatment of Pneumocystis pneumonia in non-HIV infected immunocompro-mised patients[J]. Zhongguo Linchuang Xinyixue, 2021, 14(2): 134-138.
[23]	Lu XX, Zhang JH, Ma WT, et al. Pneumocystis jirovecii pneumonia diagnosis via metagenomic next-generation sequencing[J]. Front Med (Lausanne), 2022, 9: 812005.

患儿	性别	年龄 /月	确诊 PCP 天数/d	白细胞计数 /×10⁹·L^－1	治疗后白细胞计数 /×10⁹·L^－1	复方磺胺甲噁唑		棘白菌素类		转归
患儿	性别	年龄 /月	确诊 PCP 天数/d	白细胞计数 /×10⁹·L^－1	治疗后白细胞计数 /×10⁹·L^－1	入住PICU 第n天开始	疗程/d	入住PICU 第n天开始	具体用药情况	转归
例1	女	3	8	97.3	44.3	8	4	8	卡泊芬净70 mg·m^－2·d^－1×1 d；50 mg·m^－2·d^－1×6 d	死亡
例2	女	3	3	41.2	4.0	3	23	3	卡泊芬净70 mg·m^－2·d^－1× 1d；50 mg·m^－2·d^－1×11 d	治愈
例3	女	2	7	78.3	28.6	7	11	11	米卡芬净10 mg·m^－2·d^－1×7d	死亡
例4	男	16	4	43.8	8.5	4	16	4	卡泊芬净70 mg·m^－2·d^－1×1 d；50 mg·m^－2·d^－1×14 d	治愈
例5	女	3	4	9.1	6.0	4	1	4	卡泊芬净70 mg·m^－2·d^－1×1 d；50 mg·m^－2·d^－1×1 d	死亡