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[中国南方部分地区新生儿细菌性脑膜炎的多中心流行病学研究]

[A multicenter epidemiological study of neonatal bacterial meningitis in parts of South China].

出版信息

Zhonghua Er Ke Za Zhi. 2018 Jun 2;56(6):421-428. doi: 10.3760/cma.j.issn.0578-1310.2018.06.004.

DOI:10.3760/cma.j.issn.0578-1310.2018.06.004
PMID:29886604
Abstract

To analyze the epidemiological characteristics (pathogenic bacteria distribution, clinical menifestations and outcomes) of neonatal bacterial meningitis in parts of Guangdong Province and Guangxi Zhuang Autonomous Region. A retrospective epidemiological study was carried out in the infants with bacterial meningitis admitted to 12 hospitals in Guangdong Province and Guangxi Zhuang Autonomous Region from January 2011 to December 2016. The distribution of pathogenic bacteria and epidemiological characteristics were analyzed during different periods (2011-2012, 2013-2014, 2015-2016), between early-onset and late-onset cases, preterm infants and term infants. Numeric variables between groups were compared with Student's test. Non-numeric variables were analyzed with χ(2) test. A total of 838 cases which met the criteria of neonatal bacterial meningitis were admitted during the study period, within which males were 545 and females were 293, with an average onset age of 8 (2, 16) days and diagnosed at the age of 14 (8, 20) days. Blood or CSF cultures were positive in 249 infants (29.7%), with (GBS), (), (CoNS) as the most common bacteria. The culture positive rate were 29.6% (47/159), 33.6% (85/253) and 27.5% (117/426) respectively in the periods of 2011-2012, 2013-2014, and 2015-2016, without significant differences among groups (χ(2)=2.860, 0.239). In the culture positive cases, there were no significant differences between the Gram-negative bacilli and Gram-positive cocci proportion in the three different periods (χ(2)=2.081, 0.353). The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 33.0% (64/194) and 28.7% (185/644) in early-onset and late-onset bacterium meningitis infants (χ(2)=1.297, =0.255). The differences of Gram-negative bacilli and Gram-positive cocci proportion in the two groups were statistically significant (15/49 83/103, χ(2)=8.967, 0.003), while the most common bacteria was GBS in both groups. The positive rates of CSF culture and blood culture were 26.9% (57/212) and 30.7% (192/626) in preterm infants and term infants, without significant difference between the two groups (χ(2)=0.830, 0.362). While the differences of Gram-negative bacilli and Gram-positive cocci proportion in the two groups were significant (40/18 58/134, χ(2)=28.074, 0.000), with E. coli in preterm infants while GBS in term infants. There were 45 cases (5.4%) of which cerebrospinal fluid (CSF) WBC counts were less than 20×10(6)/L when bacterial meningitis was diagnosed, among them 5 cases had positive CSF culture; there were 728 cases (90.9%, 728/801) of CSF WBC≤20×10(6)/L at discharge. The positive rate of blood culture and CSF culture were both Lower in cases treated with antibiotics > 24 hours and≤24 hours before diagnosis, with significant difference (χ(2)=19.668, 0.000). Fever was the most common clinical manifestation (633 cases, 75.5%), and hydrocephalus was the most common complication (167 cases, 19.9%), which was seen more commonly in Gram-negative bacillus cases(χ(2)=4.190, =0.041). There were 801 infants (95.6%) who were cured or improved at discharge but 13 deaths (1.6%). The median course of antibiotic before and after diagnosis were 3 days and 20 days, respectively. Single antibiotics was used in 255 (30.4%), mainly meropenem (146 cases, 57.3%) or third generation cephalosporin (67 cases, 26.3%), while combination treatment was used in 583 cases(69.6%), mainly meropenem and third generation cephalosporin (302 cases, 51.8%), or Penicillin (or vancomycin) and third generation cephalosporin (115 cases, 19.7%). There was no significant difference in efficacy between single and combined antibiotics treatment groups ( all>0.05). The most common bacteria of neonatal bacterial meningitis were GBS, and CoNS in parts of South China. GBS was the most common pathogen in both early-onset and late-onset bacterial meningitis, also most common in term infants. While the most common bacteria in preterm infants was Fever was the most common clinical manifestation and hydrocephalus was the main complication. Neonatal bacterial meningitis should not be excluded if the CSF WBC is within normal range. The positive rate of CSF or blood culture decreased significantly if antibiotic is used more than 24 hours before diagnosis. Single antibiotics for sensitive bacteria is as effective as combined antibiotics treatment.

摘要

分析广东省部分地区及广西壮族自治区新生儿细菌性脑膜炎的流行病学特征(病原菌分布、临床表现及转归)。对2011年1月至2016年12月在广东省和广西壮族自治区12家医院收治的细菌性脑膜炎患儿进行回顾性流行病学研究。分析不同时期(2011 - 2012年、2013 - 2014年、2015 - 2016年)、早发型与晚发型病例、早产儿与足月儿之间病原菌的分布及流行病学特征。组间数值变量采用Student检验进行比较。非数值变量采用χ²检验进行分析。研究期间共收治符合新生儿细菌性脑膜炎诊断标准的患儿838例,其中男545例,女293例,平均发病年龄8(2,16)天,确诊年龄14(8,20)天。249例(29.7%)患儿血培养或脑脊液培养阳性,其中以B组链球菌(GBS)、大肠埃希菌(E.coli)、凝固酶阴性葡萄球菌(CoNS)最为常见。2011 - 2012年、2013 - 2014年、2015 - 2016年各时间段培养阳性率分别为29.6%(47/159)、33.6%(85/253)和27.5%(117/426),组间差异无统计学意义(χ² = 2.860,P = 0.239)。培养阳性病例中,三个不同时期革兰阴性杆菌与革兰阳性球菌比例差异无统计学意义(χ² = 2.081,P = 0.353)。早发型和晚发型细菌性脑膜炎患儿脑脊液培养阳性率分别为33.0%(64/194)和28.7%(185/644),血培养阳性率分别为33.0%(64/194)和28.7%(185/644)(χ² = 1.297,P = 0.255)。两组革兰阴性杆菌与革兰阳性球菌比例差异有统计学意义(15/49 vs 83/103,χ² = 8.967,P = 0.003),两组最常见病原菌均为GBS。早产儿脑脊液培养阳性率为26.9%(57/212),血培养阳性率为30.7%(192/626);足月儿脑脊液培养阳性率为26.9%(57/212),血培养阳性率为30.7%(192/626),两组差异无统计学意义(χ² = 0.830,P = 0.362)。两组革兰阴性杆菌与革兰阳性球菌比例差异有统计学意义(40/18 vs 58/134,χ² = 28.074,P = 0.000),早产儿以大肠埃希菌为主,足月儿以GBS为主。确诊细菌性脑膜炎时脑脊液白细胞计数<20×10⁶/L的患儿有45例(5.4%),其中5例脑脊液培养阳性;出院时脑脊液白细胞≤20×10⁶/L的患儿有728例(90.9%,728/801)。诊断前使用抗生素>24小时及≤24小时的患儿血培养和脑脊液培养阳性率均较低,差异有统计学意义(χ² = 19.668,P = 0.000)。发热是最常见的临床表现(633例,75.5%),脑积水是最常见的并发症(167例,19.9%),革兰阴性杆菌感染病例中脑积水更为常见(χ² = 4.190,P = 0.041)。801例(95.6%)患儿出院时治愈或好转,13例死亡(1.6%)。诊断前后抗生素使用的中位疗程分别为3天和20天。255例(30.4%)患儿使用单一抗生素,主要为美罗培南(146例,57.3%)或第三代头孢菌素(67例,26.3%);583例(69.6%)患儿采用联合治疗,主要为美罗培南与第三代头孢菌素联合(302例,51.8%),或青霉素(或万古霉素)与第三代头孢菌素联合(115例,19.7%)。单一抗生素治疗组与联合抗生素治疗组疗效差异无统计学意义(P均>0.05)。华南部分地区新生儿细菌性脑膜炎最常见的病原菌为GBS、大肠埃希菌和CoNS。GBS是早发型和晚发型细菌性脑膜炎最常见的病原菌,也是足月儿最常见的病原菌。而早产儿最常见的病原菌为大肠埃希菌。发热是最常见的临床表现,脑积水是主要并发症。脑脊液白细胞在正常范围时不能排除新生儿细菌性脑膜炎。诊断前使用抗生素超过24小时脑脊液或血培养阳性率显著降低。针对敏感菌的单一抗生素治疗与联合抗生素治疗效果相当。

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