新生儿念珠菌血症发生及预后不良的危险因素

doi:10.16150/j.1671-2870.2026.03.008

摘要/Abstract

摘要：

目的：分析新生儿念珠菌血症发生危险因素及预后不良危险因素，为临床诊治提供依据。方法：2017年1月至2024年12月，收集在上海市儿童医院新生儿病区通过血培养检出念珠菌确诊的感染时日龄≤28 d的57例新生儿念珠菌血症连续病例，分析患儿的临床特点、实验室检测和治疗情况。根据结局，将患儿分为死亡组（5例）和好转组（52例），分析新生儿念珠菌血症发生及预后不良危险因素。结果：57例新生儿念珠菌血症病例中，男性30例，女性27例，发生念珠菌血症时的中位日龄为14 d（四分位距10，20）。48例（84.21%）为早产儿（<37周），46例（80.7%）为低出生体重儿（<2 500 g），54例（94.7%）在发生念珠菌感染前有侵入性检查治疗操作史，55例（96.5%）在念珠菌感染前有抗菌药物使用史。病原学分析显示，患儿感染的念珠菌以近平滑念珠菌（46例，80.7%）为主，之后依次为白念珠菌（6例，10.53%）、光滑念珠菌（3例，5.26%）和季也蒙念珠菌（2例3.51%）。药敏检测结果显示无抗真菌药物耐药株。患儿从临床发生症状到确诊并进行抗真菌治疗的时长为（2.3±1.2） d，抗真菌治疗时长为29 d（四分位距23，37）。单因素分析显示，感染性休克、气管插管/机械通气、血小板计数（platelet，PLT）降低及降钙素原（procalcitonin，PCT）升高是新生儿念珠菌血症患儿死亡的危险因素（P<0.05）。结论：新生儿念珠菌血症发生的危险因素包括早产、低出生体重、有侵入性检查治疗操作史以及抗菌药物使用史，患儿感染的念珠菌以近平滑念珠菌为主。感染性休克、气管插管/机械通气是念珠菌血症新生儿死亡的危险因素，PLT和PCT可作为评估患儿预后的重要参考指标。

关键词: 新生儿, 念珠菌血症, 近平滑念珠菌, 预后危险因素

Abstract:

Objective This study aims to analyze the risk factors for the occurrence of neonatal candidemia and those associated with poor prognosis, thereby providing evidence for clinical diagnosis and treatment. Methods This retrospective study enrolled consecutive 57 cases of neonatal candidemia diagnosed by blood culture in the neonatal ward of Shanghai Children's Hospital between January 2017 and December 2024. All included neonates aged ≤28 days at the time of infection. The clinical features, laboratory findings, and treatment outcomes were analyzed. According to outcomes, the neonates were divided into death group (5 cases) and improved group (52 cases), and the risk factors for poor prognosis were analyzed. Results Among the 57 neonates with candidemia, 30 were male and 27 were female. The median postnatal age at the onset of candidemia was 14 days (interquartile range, 10, 20). Forty-eight cases (84.21%) were preterm infants (<37 weeks), 46 cases (80.7%) were low birth weight infants (<2 500 g), 54 cases (94.7%) had a history of invasive examination and treatment procedures before the onset of candidiasis, and 55 cases (96.5%) had a history of antimicrobial agent use prior to candidiasis. Etiological analysis showed that the predominant Candida species infecting the neonates was Candida parapsilosis (46 cases, 80.7%), follower by Candida albicans (6 cases, 10.53%), Candida glabrata (3 cases, 5.26%), and Candida guilliermondii (2 cases, 3.51%). Drug susceptibility test results indicated there was no antifungal drug-resistant strains. The time from the onset of clinical symptoms to confirmed diagnosis and initiation of antifungal therapy was (2.3±1.2) days, and the duration of antifungal treatment was 29 days (interquartile range, 23, 37). Univariate analysis showed that septic shock, tracheal intubation/mechanical ventilation, decreased platelet (PLT) count, and elevated procalcitonin (PCT) were risk factors for poor prognosis of neonatal candidemia (P<0.05). Conclusions The risk factors for neonatal candidemia include prematurity, low birth weight, a history of invasive examination and treatment procedures, and a history of antimicrobial drug use. The predominant pathogenic Candida species is Candida parapsilosis. Septic shock and endotracheal intubation/mechanical ventilation are risk factors for poor prognosis of neonatal candidemia. PLT and PCT can serve as important reference indicators for evaluating the prognosis of neonatal candidemia.

Key words: Neonate, Candidemia, Candida parapsilosis, Prognostic risk factors

中图分类号:

R446
R519.3

秦惠宏, 于方圆, 蒋婕, 张天栋, 潘芬. 新生儿念珠菌血症发生及预后不良的危险因素[J]. 诊断学理论与实践, 2026, 25(03): 321-326.

QIN Huihong, YU Fangyuan, JIANG Jie, ZHANG Tiandong, PAN Fen. Risk factors for occurrence and poor prognosis of neonatal candidemia[J]. Journal of Diagnostics Concepts & Practice, 2026, 25(03): 321-326.

图/表 2

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参考文献 27

[1]	BENEDICT K, ROY M, KABBANI S, et al. Neonatal and pediatric candidemia: Results from population-based active laboratory surveillance in four US locations, 2009-2015[J]. J Pediatr Infect Dis Soc, 2018, 7(3):e78-e85. doi: 10.1093/jpids/piy009 URL
[2]	HSU J F, LAI M Y, LEE C W, et al. Comparison of the incidence, clinical features and outcomes of invasive candidiasis in children and neonates[J]. BMC Infect Dis, 2018, 18(1):194. doi: 10.1186/s12879-018-3100-2
[3]	潘冰婷, 瞿跃, 朱敏丽, 等. 新生儿侵袭性真菌感染90例的临床分析[J]. 中华传染病杂志, 2020, 38(11):735-739.
	PAN B T, QU Y, ZHU M L, et al. Clinical analysis of 90 cases of neonatal invasive fungal infection[J]. Chin J Infect Dis, 2020, 38(11):735-739.
[4]	余时娟, 李禄全. 新生儿真菌性败血症23例临床分析[J]. 临床儿科杂志, 2014(9):816-820.
	YU S J, LI L Q. Clinical analysis for fungal septicemia in 23 neonates[J]. J Clin Pediatr, 2014(9):816-820.
[5]	WEIMER K E D, SMITH P B, PUIA-DUMITRESCU M, et al. Invasive fungal infections in neonates: A review[J]. Pediatr Res, 2022, 91(2):404-412. doi: 10.1038/s41390-021-01842-7
[6]	赖晓全, 于孟, 陈金敏. 新生儿真菌血症的调查与分析[J]. 医学与哲学, 2011, 32(24):40-41,50.
	LAI X Q, YU M, CHEN J M. Investigation and analysis on fungemia in neonates[J]. Med Philos, 2011, 32(24):40-41,50.
[7]	陈海花, 崔杰, 唐洪怡, 等. 新生儿重症监护病房患儿侵袭性真菌感染流行病学变迁[J]. 中华围产医学杂志, 2017, 20(8):577-582.
	CHEN H H, CUI J, TANG H Y, et al. Epidemiological changes in invasive fungal infection in a neonatal intensive care unit[J]. Chin J Perinat Med, 2017, 20(8):577-582.
[8]	李志玲, 徐峰, 杨传忠, 等. 极低出生体质量儿非白念珠菌血流感染病原菌及药敏特性[J]. 中国感染与化疗杂志, 2016, 16(5):551-556.
	LI Z L, XU F, YANG C Z, et al. Distribution and susceptibility of Candida species in non-albicans bloodstream infections in very low birth weight infants[J]. Chin J Infect Chemother, 2016, 16(5):551-556.
[9]	BENJAMIN D K JR, STOLL B J, GANTZ M G, et al. Neonatal candidiasis: Epidemiology, risk factors, and clinical judgment[J]. Pediatrics, 2010, 126(4):e865-e873. doi: 10.1542/peds.2009-3412 URL
[10]	中华医学会儿科学分会新生儿学组, 中华儿科杂志编辑委员会. 新生儿败血症诊断与治疗专家共识(2024)[J]. 中华儿科杂志, 2024, 62(10):931-940.
	The Subspecialty Group of Neonatology, the Society of Pediatrics, Chinese Medical Association; the Editorial Board, Chinese Journal of Pediatrics. Expert consensus on diagnosis and management of neonatal bacteria sepsis (2024)[J]. Chin J Pediatr, 2024, 62(10):931-940.
[11]	中国医师协会血液科医师分会, 中国侵袭性真菌感染工作组. 血液病/恶性肿瘤患者侵袭性真菌病的诊断标准与治疗原则(第七次修订版)[J]. 中华内科杂志, 2025, 64(12):1155-1168.
	Chinese Association Hematologists; Chinese Invasive Fungal Infection Working Group. The Chinese guidelines for the diagnosis and treatment of invasive fungal disease in patients with hematological disorders and cancers (the seventh revision)[J]. Chin J Intern Med, 2025, 64(12):1155-1168.
[12]	Clinical and Laboratory standards Institute.Perfbrmance standards for antifungal susceptibility testing of yeasts. 3rd ed. CLSI supplement M27M44S[S]. Wayne, PA:CLSI, 2022.
[13]	Clinical and Laboratory standards lnstitute.E pidemiological cut of R values for antifhngal susceptibity testing. 4th ed. CLSI supplement M57S[S]. Wayne, PA:CLSI, 2022.
[14]	STOLL B J, HANSEN N. Infections in VLBW infants: Studies from the NICHD neonatal research network[J]. Semin Perinatol, 2003, 27(4):293-301. doi: 10.1016/s0146-0005(03)00046-6 pmid: 14510320
[15]	KAUFMAN D. Strategies for prevention of neonatal invasive candidiasis[J]. Semin Perinatol, 2003, 27(5):414-424. pmid: 14626506
[16]	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.
	LI Y B, XU Y C, ZHANG L. Invasive fungal infections in children should not be underestimated[J]. Chin J Appl Clin Pediatr, 2024, 39(1):2-6.
[17]	YAMIN D H, HUSIN A, HARUN A. Risk factors of Candida parapsilosis catheter-related bloodstream infection[J]. Front Public Health, 2021,9:631865.
[18]	YU Y, YUAN T, ZHENG J, et al. Risk factors and clinical analysis for invasive fungal infection in neonatal intensive care unit patients[J]. Amer J Perinatol, 2013, 30(7):589-594. doi: 10.1055/s-00000009 URL
[19]	XIAO M, SUN ZY, KANG M, et al. Five-Year national surveillance of invasive Candidiasis: Species distribution and azole susceptibility from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study[J]. J Clin Microbiol, 2018; 56(7):e00577-18.
[20]	HOU S, WANG X, YU Y, et al. Invasive fungal infection is associated with antibiotic exposure in preterm infants: A multi-centre prospective case-control study[J]. J Hosp Infect, 2023,134:43-49.
[21]	DELFINO D, SCORDINO F, PERNICE I, et al. Potential association of specific Candida parapsilosis genotypes, bloodstream infections and colonization of health workers' hands[J]. Clin Microbiol Infect, 2014, 20(11):O946-O951.
[22]	WANG Y S, HSU J F, LEE W J, et al. Invasive Candida parapsilosis bloodstream infections in children: The antifungal susceptibility, clinical characteristics and impacts on outcomes[J]. Microorganisms, 2023, 11(5):1149. doi: 10.3390/microorganisms11051149 URL
[23]	DAVIS M R, NGUYEN M H, DONNELLEY M A, et al. Tolerability of long-term fluconazole therapy[J]. J Antimicrob Chemother, 2019, 74(3):768-771. doi: 10.1093/jac/dky501 pmid: 30535104
[24]	蒲东亚, 张玉林, 雷子辰, 等. 成人念珠菌血症的临床特点及死亡危险因素分析[J]. 中华检验医学杂志, 2026, 49(2):188-194.
	PU D Y, ZHANG Y L, LEI Z C, et al. Analysis of clinical characteristics and risk factors for mortality in adult candidemia[J]. Chin J Lab Med, 2026, 49(2):188-194.
[25]	俞娟芬, 张亚峰, 张建国, 等. 真菌血流感染病原学与临床特点及其预后危险因素[J]. 中华医院感染学杂志, 2022, 32(6):852-856.
	YU J F, ZHANG Y F, ZHANG J G, et al. Etiological and clinical characteristics of patients with fungal bloodstream infection and risk factors for prognosis[J]. Chin J Nosocomiol, 2022, 32(6):852-856.
[26]	田鹏鹏, 王娴默, 易华伟. 55例念珠菌血症的临床与实验室特点分析[J]. 中国真菌学杂志, 2024, 19(4):337-341.
	TIAN P P, WANG X M, YI H W. Analysis of clinical and laboratory characteristics of 55 cases of candidemia[J]. Chin J Mycol, 2024, 19(4):337-341.
[27]	HEGAZI M, ABDELKADER A, ZAKI M, et al. Characteristics and risk factors of candidemia in pediatric intensive care unit of a tertiary care children’s hospital in Egypt[J]. J Infect Dev Ctries, 2014, 8(5):624-634. doi: 10.3855/jidc.4186 URL

Candida species (n)	Fluconazole	Itraconazole	Voriconazole	Posaconazole	Anidulafungin	Caspofungin	Micafungin	Flucytosine	Amphotericin B
Candida parapsilosis (46)	100%	NA	100%	NA	100%	100%	100%	NA	NA
Candida albicans (6)	66.7%	NA	66.7%	NA	100%	100%	100%	NA	NA
Candida glabrata (3)	NA	NA	NA	NA	100%	100%	100%	NA	NA
Candida guilliermondii (2)	NA	NA	NA	NA	100%	100%	100%	NA	NA

Variables	Death (n=5)	Improvement (n=52)	Statistic	P value
Gestational age (weeks)	31.2 (29.2, 33.5)	32.0 (29.4, 34.4)	Z=-0.31	0.754
Birth weight (g)	1 600 (1 170, 1 715)	1 765 (1 373, 2 125)	Z=-1.81	0.071
Male sex [n (%)]	3 (60.0)	25 (48.1)	—	0.682
Respiratory diseases [n (%)]	5 (100.0)	41 (78.8)	—	0.264
Gastrointestinal diseases [n (%)]	3 (60.0)	17 (32.7)	—	0.170
Cardiac diseases [n (%)]	4 (80.0)	41 (78.8)	—	1.000
Central nervous system diseases [n (%)]	3 (60.0)	21 (40.4)	—	0.380
Septic shock [n (%)]	4 (80.0)	2 (3.8)	—	<0.001
Endotracheal intubation / mechanical ventilation [n (%)]	5 (100.0)	22 (42.3)	—	0.008
Surgery [n (%)]	1 (20.0)	5 (9.6)	—	0.554
Central venous catheter [n (%)]	2 (40.0)	7 (13.5)	—	0.082
White blood cell count (×10⁹/L)	6.20 (3.44, 10.12)	8.21 (5.35, 11.91)	Z=-1.16	0.248
Platelet count (×10⁹/L)	44(38， 86)	128(74, 193)	Z=-2.243	0.026
C-reactive protein (mg/L)	28 (20, 30)	7 (1, 23)	Z=-1.89	0.059
Procalcitonin (ng/mL)	1.45 (1.34, 1.8)	0.48(0.28, 0.82)	Z=2.003	0.047