新生儿败血症病原学特征及革兰阴性菌感染影响因素分析——基于5年临床分析

doi:10.12372/jcp.2024.23e0661

Abstract

Abstract:

Objective To investigate the distribution and drug resistance of bacteria in neonatal sepsis and to identify the influence factor for gram-negative (G^-) bacterial infection. Methods The clinical data of patients diagnosed with neonatal sepsis admitted from January 1, 2018 to December 31, 2022 were collected, and the characteristics and drug resistance of major pathogenic bacteria were analyzed. Based on the pathogenic bacteria's gram staining results, all patients were categorized into groups of gram-positive (G⁺) and G^- bacteria. The influencing factors for G^- bacterial infection were analyzed by binary logistic regression, and the value of each factor was evaluated according to the area under the receiver operating characteristic curve (AUC). Results A total of 208 strains of pathogenic bacteria were detected in 201 neonatal sepsis patients, of which 126 (60.6%) were G⁺ bacteria and 82 (39.4%) were G^- bacteria. Coagulase negative staphylococci (CoNS) was the most common G⁺ bacteria with high resistance to penicillin, erythromycin and oxacillin. Klebsiella pneumoniae was the most common G^- bacteria with high resistance to penicillins and cephalosporins. Comparing the proportion of pathogenic bacteria in different years, it was found that the proportion of G^- bacteria showed an increasing trend in the past five years. According to the results of pathogen gram staining, 201 patients were divided into G⁺ bacteria group (n=119) and G^- bacteria group (n=82). Univariate analysis and binary logistic regression analysis showed that hospital-acquired infection, white blood cell count (WBC) < 5×10⁹/L, C-reactive protein (CRP) and procalcitonin (PCT) were the influential factors in differentiating G^- bacterial infection (P<0.05). The AUC of the combination of the above influencing factors for identifying G^- bacterial infection was 0.888 (95%CI: 0.840~0.936, P<0.01). Conclusions CoNS and Klebsiella pneumoniae were the main pathogens of neonatal sepsis. The proportion of G- bacterial infection showed an increasing trend from 2018 to 2022. Hospital-acquired infection, WBC<5×10⁹/L and higher CRP and PCT levels were risk factors for G^- bacterial infection. The combination of hospital-acquired infection, WBC<5×10⁹/L, CRP and PCT had high predictive value for G^- bacterial infection.

Key words: antimicrobial resistance, gram-negative bacteria, risk factor, neonatal sepsis

BIAN Zhaonan, ZHA Xinyi, ZHANG Xi, CHEN Xuting, CHEN Yanru, XU Min, ZHANG Yonghong, QIAN Jihong. Pathogenic characteristics of neonatal sepsis and influence factors of gram-negative bacterial infection: based on a 5-year retrospective clinical study[J].Journal of Clinical Pediatrics, 2024, 42(3): 204-210.

Figures/Tables 6

项目	革兰阳性菌(n=119)	革兰阴性菌(n=82)	统计量	P
性别（男）[n(%)]	78（65.5）	51（62.2）	χ²=0.24	0.655
日龄[M(P₂₅~P₇₅)]/d	15（7~22）	13（8~20）	Z=0.01	0.994
早产儿[n(%)]	29（24.4）	45（54.9）	χ²=19.43	<0.01
剖宫产[n(%)]	64（53.8）	45（54.9）	χ²=0.02	0.887
出生体重[M(P₂₅~P₇₅)]/g	3 200（2 650~3 625）	2 655（1 480~3 160）	Z=5.13	<0.01
羊水污染[n(%)]	17（14.3）	5（6.1）	χ²=3.34	0.106
胎膜早破[n(%)]	10（8.4）	17（20.7）	χ²=6.35	0.019
产前激素使用[n(%)]	6（5.0）	22（26.8）	χ²=19.22	<0.01
院内感染[n(%)]	15（12.6）	47（57.3）	χ²=45.50	<0.01
N%(x±s)/%	51.1±18.9	59.2±21.2	t=2.82	<0.01
WBC[M(P₂₅~P₇₅)]/×10⁹·L^-1	10.52（8.48~14.48）	12.17（6.74~16.54）	Z=0.05	0.961
WBC<5×10⁹·L^-1[n(%)]	9（7.6）	15（18.3）	χ²=5.32	0.027
CRP[M(P₂₅~P₇₅)]/mg·L^-1	8（8~19）	52（22~86）	Z=8.16	<0.01
PCT[M(P₂₅~P₇₅)]/ng·mL^-1	0.25（0.12~1.71）	10.83（1.88~44.48）	Z=8.17	<0.01
血小板计数[M(P₂₅~P₇₅)]/×10⁹·L^-1	310（216~392）	176（98~300）	Z=4.88	<0.01
发热[n(%)]	70（58.8）	47（57.3）	χ²=0.05	0.885
皮肤黄染[n(%)]	60（50.4）	39（47.6）	χ²=0.16	0.774
水肿[n(%)]	2（1.7）	10（12.2）	χ²=7.78	<0.01
嗜睡[n(%)]	9（7.6）	3（3.7）	χ²=0.72	0.398
腹胀[n(%)]	12（10.1）	29（35.4）	χ²=19.11	<0.01
吃奶差[n(%)]	13（10.9）	4（4.9）	χ²=2.29	0.196
精神差、反应低下[n(%)]	11（9.2）	15（18.3）	χ²=3.53	0.086
呕吐[n(%)]	13（10.9）	5（6.1）	χ²=1.39	0.317
皮肤表现¹⁾[n(%)]	22（18.5）	18（22.0）	χ²=0.37	0.592
青紫[n(%)]	7（5.9）	6（7.3）	χ²=0.17	0.773
脐部异常[n(%)]	13（10.9）	2（2.4）	χ²=5.06	0.028
呼吸道、消化道出血[n(%)]	2（1.7）	8（9.8）	χ²=5.10	0.024
四肢冷、低体温[n(%)]	8（6.7）	12（14.6）	χ²=3.39	0.066
呼吸暂停、呼吸困难[n(%)]	6（5.0）	13（15.9）	χ²=6.63	0.010
心动过速[n(%)]	3（2.5）	8（9.8）	χ²=3.61	0.057

References 28

[1]	中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会. 新生儿败血症诊断及治疗专家共识(2019年版)[J]. 中华儿科杂志, 2019, 57(4): 252-257.
[2]	Egbe FN, Cowden C, Mwananyanda L, et al. Etiology of bacterial sepsis and isolate resistance patterns in hospitalized neonates in Zambia[J]. Pediatr Infect Dis J, 2023, 10.1097/INF.0000000000004008.
[3]	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.
[4]	Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, et al. The global burden of paediatric and neonatal sepsis: a systematic review[J]. Lancet Respir Med, 2018, 6(3): 223-230. doi: 10.1016/S2213-2600(18)30063-8 pmid: 29508706
[5]	Zhang J, Chen L, Yang Y, et al. Clinical and laboratory findings to differentiate late-onset sepsis caused by Gram-negative vs Gram-positive bacteria among perterm neonates: A retrospective cohort study[J]. Int Immunopharmacol, 2023, 116: 109769. doi: 10.1016/j.intimp.2023.109769
[6]	Wu IH, Tsai MH, Lai MY, et al. Incidence, clinical features, and implications on outcomes of neonatal late-onset sepsis with concurrent infectious focus[J]. BMC Infect Dis, 2017, 17(1): 465. doi: 10.1186/s12879-017-2574-7 pmid: 28673280
[7]	张良娟, 施姣, 杨军兰, 等. 新生儿重症监护室晚发型败血症病原菌变迁及耐药性分析[J]. 临床儿科杂志, 2022, 40(8): 602-607.
[8]	俞元强, 董青艺, 胡劲涛, 等. 新生儿败血症病原菌及耐药性10年回顾性分析[J]. 中国当代儿科杂志, 2022, 24(10): 1111-1116.
[9]	昌兰, 吴银弟, 李朝友. 228例新生儿败血症的病原体分布耐药性及临床特点[J]. 中国妇幼保健, 2022, 37(23): 4401-4405.
[10]	徐俊芳, 平莉莉, 翟淑芬. 不同新生儿败血症病原菌、耐药性及影响因素研究[J]. 中国妇幼健康研究, 2022, 33(8): 6-11.
[11]	陈云波, 嵇金如, 刘志盈, 等. 全国血流感染细菌耐药监测(BRICS)2021年度报告[J]. 中华临床感染病杂志, 2023, 16(1): 33-47.
[12]	宋岐峰, 李国福, 臧彬. 重症监护病房病原菌分布及耐药性趋势分析[J]. 中国中西医结合急救杂志, 2022, 29(1): 17-21.
[13]	Liu J, Fang Z, Yu Y, et al. Pathogens distribution and antimicrobial resistance in bloodstream infections in twenty-five neonatal intensive care units in China, 2017-2019 [J]. Antimicrob Resist Infect Control, 2021, 10(1): 121. doi: 10.1186/s13756-021-00989-6
[14]	Giannoni E, Agyeman PKA, Stocker M, et al. Neonatal sepsis of early onset, and hospital-acquired and community-acquired late onset: a prospective population-based cohort study[J]. J Pediatr, 2018, 201: 106-114. doi: 10.1016/j.jpeds.2018.05.048
[15]	Jean-Baptiste N, Benjamin DK, Cohen-Wolkowiez M, et al. Coagulase-negative staphylococcal infections in the neonatal intensive care unit[J]. Infect Control Hosp Epidemiol, 2011, 32(7): 679-686. doi: 10.1086/660361
[16]	Von Dolinger De Brito D, De Almeida Silva H, Jose Oliveira E, et al. Effect of neonatal intensive care unit environment on the incidence of hospital-acquired infection in neonates[J]. J Hosp Infect, 2007, 65(4): 314-318. pmid: 17350722
[17]	Osei Sekyere J, Reta MA, Bernard Fourie P. Risk factors for, and molecular epidemiology and clinical outcomes of, carbapenem- and polymyxin-resistant Gram-negative bacterial infections in pregnant women, infants, and toddlers: a systematic review and meta-analyses[J]. Ann N Y Acad Sci, 2021, 1502(1): 54-71. doi: 10.1111/nyas.v1502.1
[18]	杨新梅. 新生儿病房内医院感染的现状与危险因素[J]. 国际护理学杂志, 2023, 42(2): 235-238.
[19]	Gao H, Evans TW, Finney SJ. Bench-to-bedside review: sepsis, severe sepsis and septic shock - does the nature of the infecting organism matter?[J]. Crit Care, 2008, 12(3): 213.
[20]	Feezor RJ, Oberholzer C, Baker HV, et al. Molecular characterization of the acute inflammatory response to infections with gram-negative versus gram-positive bacteria[J]. Infect Immun, 2003, 71(10): 5803-5813. doi: 10.1128/IAI.71.10.5803-5813.2003 pmid: 14500502
[21]	Abe R, Oda S, Sadahiro T, et al. Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia[J]. Crit Care, 2010, 14(2): R27. doi: 10.1186/cc8898
[22]	Wang B, Wang QM, Li DX. An Analysis of Predictive Factors for Severe Neonatal Infection and the Construction of a Prediction Model[J]. Infect Drug Resist, 2023, 16: 3561-3574. doi: 10.2147/IDR.S408126 pmid: 37305733
[23]	Guo J, Luo Y, Wu Y, et al. Clinical characteristic and pathogen spectrum of neonatal sepsis in Guangzhou city from June 2011 to June 2017[J]. Med Sci Monit, 2019, 25: 2296-2304. doi: 10.12659/MSM.912375
[24]	RESCH B, B R, N H. Comparison between pathogen associated laboratory and clinical parameters in early-onset sepsis of the newborn[J]. Open Microbiol J, 2016, 10: 133-139. doi: 10.2174/1874285801610010133 pmid: 27478518
[25]	Liu HH, Zhang MW, Guo JB, et al. Procalcitonin and C-reactive protein in early diagnosis of sepsis caused by either Gram-negative or Gram-positive bacteria[J]. Ir J Med Sci, 2017, 186(1): 207-212. doi: 10.1007/s11845-016-1457-z
[26]	Brodská H, Malíčková K, Adámková V, et al. Significantly higher procalcitonin levels could differentiate Gram-negative sepsis from Gram-positive and fungal sepsis[J]. Clin Exp Med, 2013, 13(3): 165-170. doi: 10.1007/s10238-012-0191-8 pmid: 22644264
[27]	王丽伟, 刘丽红, 李达. 降钙素原对儿童不同类型病原菌血流感染的诊断价值[J]. 临床血液学杂志, 2019, 32(6): 423-425.
[28]	For The Medusa Study Group, Thomas-Rüddel DO, Poidinger B, et al. Influence of pathogen and focus of infection on procalcitonin values in sepsis patients with bacteremia or candidemia[J]. Crit Care, 2018, 22(1): 128. doi: 10.1186/s13054-018-2050-9

病原菌	例数	构成比/%
革兰阳性菌	126	60.6
凝固酶阴性葡萄球菌	73	35.1
表皮葡萄球菌	52	25.0
人型葡萄球菌	11	5.3
溶血葡萄球菌	5	2.4
头状葡萄球菌	3	1.4
华纳葡萄球菌	1	0.5
沃氏葡萄球菌	1	0.5
粪肠球菌	13	6.3
屎肠球菌	12	5.8
金黄色葡萄球菌	12	5.8
无乳链球菌	10	4.8
李斯特菌	3	1.4
血链球菌	1	0.5
副血链球菌	1	0.5
弯曲芽孢杆菌	1	0.5
革兰阴性菌	82	39.4
肺炎克雷伯菌	44	21.2
大肠埃希菌	24	11.5
阴沟肠杆菌	4	1.9
产气克雷伯菌	3	1.4
鲍曼不动杆菌	2	1.0
产气肠杆菌	2	1.0
拜尔利氏不动杆菌	1	0.5
粘质沙雷菌	1	0.5
铜绿假单胞菌	1	0.5
合计	208	100

因素	β	SE	Wald χ²值	P	OR（95% CI）
院内感染	1.949	0.423	21.24	<0.001	7.019（3.065~16.076）
WBC<5×10⁹·L^-1	1.286	0.575	5.01	0.025	3.618（1.173~11.159）
CRP	0.032	0.007	19.77	<0.001	1.032（1.018~1.047）
PCT	0.033	0.014	5.74	0.017	1.034（1.006~1.062）
常量	-1.028	0.341	9.10	0.003	0.358

Pathogenic characteristics of neonatal sepsis and influence factors of gram-negative bacterial infection: based on a 5-year retrospective clinical study

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