儿童急性白血病伴侵袭性肺部真菌感染的临床特点、真菌分布及影响因素分析

Clinical characteristics, fungal distribution and influencing factors of invasive pulmonary fungal infection in children with acute leukemia

摘要:

目的 分析儿童急性白血病伴侵袭性肺部真菌感染（IPFI）的临床特点、真菌分布及影响因素。方法 回顾性分析2018年1月—2022年12月安徽省儿童医院82例急性白血病患儿的临床资料，按照是否合并IPFI分为IPFI组（18例）和非IPFI组（64例）。比较两组患儿的一般临床资料；采用多因素一般Logistic回归模型分析儿童急性白血病伴IPFI的危险因素；分析IPFI组患儿的临床特征、真菌菌种分布。结果 18例IPFI患儿均有不同程度的发热，体温>38.5 ℃占比72.22%，咳嗽咳痰/白色黏痰占比83.33%；18例IPFI患儿中5例表现为结节实变影，7例表现为多发斑片状阴影，8例表现为散在斑片状阴影合并小结节，2例表现多发云雾状毛玻璃样高密度影、间质病变为主。16例获得真菌微生物学证据，血培养2例，肺泡灌洗液涂片1例，血或者肺泡灌洗液NGS检测13例，其中以毛霉菌（31.25%）、曲霉菌（25.00%）、近平滑假丝酵母菌（18.75%）为主；多因素一般Logistic回归分析结果显示，化疗方案含激素［O^R=2.152（95% CI：1.018，7.652）］、广谱抗生素使用时间≥7 d ［O^R=3.218（95% CI：1.091，9.492）］、中性粒细胞缺乏时间≥ 10 d ［O^R=3.818（95% CI：1.262，11.556）］、抗菌药物使用种类≥ 2种［O^R=5.810（95% CI：1.166，28.939）］均是儿童急性白血病伴IPFI的危险因素（P <0.05）。结论 儿童急性白血病伴IPFI发生率高，以假丝酵母菌为主，患儿常伴有发热、咳嗽咳痰等症状；化疗方案含激素、广谱抗生素使用时间≥ 7 d、中性粒细胞缺乏时间≥ 10 d、抗菌药物使用种类≥ 2种是儿童急性白血病伴IPFI的危险因素，临床应针对风险因素制订相应措施。

Abstract:

Objective To analyze the clinical features, fungal distribution, and influencing factors of invasive pulmonary fungal infections (IPFI) in children with acute leukemia.Methods A retrospective analysis of clinical data from 82 pediatric patients with acute leukemia treated at Anhui Children's Hospital between January 2018 and December 2022 was conducted. Patients were categorized into IPFI (18 cases) and non-IPFI (64 cases) groups based on the presence of IPFI. General clinical data of both groups were compared. Multifactorial logistic regression analysis was used to identify risk factors for IPFI in children with acute leukemia. Clinical features and fungal species distribution in the IPFI group were also analyzed.Results All 18 patients with IPFI exhibited varying degrees of fever, with 72.22% having a temperature > 38.5 °C, and 83.33% had cough with sputum or white mucus. Radiological findings in the IPFI group included nodular consolidation in 5 cases, multiple patchy shadows in 7 cases, scattered patchy shadows combined with small nodules in 8 cases, and multiple ground-glass opacities in 2 cases, with predominant interstitial involvement. Sixteen patients provided mycological evidence, including 2 blood cultures, 1 bronchoalveolar lavage fluid smear, and 13 Next-Generation Sequencing (NGS) tests of blood or bronchoalveolar lavage fluid. Predominant fungi species included Aspergillus (31.25%), Candida (25.00%), and Pneumocystis jirovecii (18.75%). Multifactorial logistic regression analysis showed that chemotherapy regimens containing steroids [O^R = 2.152 (95% CI: 1.018, 7.652) ], broad-spectrum antibiotic use ≥ 7 days [O^R = 3.218 (95% CI: 1.091, 9.492) ], neutropenia duration ≥ 10 days [O^R = 3.818 (95% CI: 1.262, 11.556) ], and use of ≥ 2 types of antimicrobial drugs [O^R = 5.810 (95% CI: 1.166, 28.939) ] were all significant risk factors for IPFI in children with acute leukemia (P < 0.05).Conclusion IPFI has a high incidence in children with acute leukemia, with predominant fungal species being Aspergillus and Candida. Symptoms typically include fever, cough, and sputum production. Risk factors for IPFI in these children include chemotherapy regimens containing steroids, prolonged use of broad-spectrum antibiotics, prolonged neutropenia, and multiple types of antimicrobial drug use. Appropriate measures should be taken based on these risk factors in clinical management.