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

摘要/Abstract

摘要：

目的了解新生儿败血症病原菌分布及耐药情况，筛选用于鉴别革兰阴性菌感染的影响因素。方法收集2018年1月1日至2022年12月31日收治的确诊新生儿败血症患儿的临床资料，分析病原菌特征和主要病原菌耐药情况，根据病原菌革兰染色结果分为革兰阴性菌(G^-菌)组和革兰阳性菌(G⁺菌)组，通过二分类logistic回归分析G^-菌感染的影响因素，并根据受试者工作特征曲线下面积（AUC）进行鉴别价值的评价。结果 201例新生儿确诊败血症患儿共检出208株病原菌，其中G⁺菌126株（60.6%），G^-菌82株（39.4%）。G⁺菌主要为凝固酶阴性葡萄球菌(CoNS)，对青霉素、红霉素和苯唑西林耐药程度较高。G^-菌主要为肺炎克雷伯菌，对青霉素类和头孢菌素类耐药程度较高。对比不同年度病原菌占比情况发现G^-菌在过去5年占比呈现上升趋势。201例患儿按照病原菌革兰染色结果分为G⁺菌组（n=119）和G^-菌组（n=82），单因素分析和二分类logistic回归分析结果显示院内感染，白细胞计数(WBC)<5×10⁹/L，C-反应蛋白（CRP）和降钙素原（PCT）是鉴别G^-菌感染的影响因素（P<0.05）。联合上述影响因素鉴别G^-菌感染的曲线下面积（AUC）=0.888 (95%CI：0.840~0.936，P<0.01）。结论新生儿败血症患儿的病原菌主要以CoNS和肺炎克雷伯菌为主，G^-菌感染在2018—2022年间的占比呈上升趋势。院内感染、WBC<5×10⁹/L和更高的CRP、PCT水平是G^-菌感染的影响因素。联合院内感染、WBC<5×10⁹/L、CRP和PCT对G^-菌感染具有较高的鉴别价值。

关键词: 抗生素耐药, 革兰阴性菌, 危险因素, 新生儿败血症

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

卞赵男, 查新祎, 张熙, 陈旭婷, 陈彦如, 许敏, 张永红, 钱继红. 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[J]. 临床儿科杂志, 2024, 42(3): 204-210.

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.

图/表 6

表1

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图2

表2

G-菌和G+菌感染患儿临床资料分析"

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

表2

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参考文献 28

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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