新生儿脲原体脑膜炎2例并文献复习

Neonatal ureaplasma meningitis:a report of 2 cases and literature review

目的探讨新生儿脲原体脑膜炎的临床特征和诊治方式。方法回顾性分析2021年湖南省儿童医院新生儿科收治的2例新生儿脲原体脑膜炎患儿临床资料,以“新生儿”、“早产儿”、“脲原体”、“解脲支原体”、“脑膜炎”、“颅内感染”、“中枢神经系统感染”、“脑炎”、“infant”、“neonate”、“newborn”、“ureaplasma”、“mycoplasma urealytium”、“meningitis”、“central nervous system infection”、“brain”为检索词,检索中国知网、万方数据库、中华医学期刊全文数据库、维普数据库、中国生物医学文献服务系统、PubMed、Embase和Web of Science自建库至2022年3月的相关文献,总结新生儿脲原体脑膜炎的临床特点、诊疗经过及预后。结果病例1,女,胎龄33+3周,生后第2天发现颅内出血及脑室扩张,脑脊液检测示脑膜炎、培养阴性,抗感染治疗无好转。生后30 d脑脊液宏基因组二代测序(metagenomic next-generation sequencing,mNGS)及23S rRNA检测提示解脲脲原体感染。多西环素治疗21 d,mNGS转阴但停多西环素23 d后脑脊液mNGS、解脲脲原体培养再次提示解脲脲原体感染,改多西环素和红霉素二联抗感染。随访至6月龄无神经系统发育迟滞。病例2,男,胎龄26周,生后第10天发现颅内出血及脑室扩张,脑脊液检测示脑膜炎、培养阴性,抗感染治疗无好转。生后28 d脑脊液mNGS及23S rRNA检测提示微小脲原体感染,红霉素治疗32 d。随访至5月龄无神经系统发育迟滞。共检索到27篇文献,41例新生儿脲原体脑膜炎患儿,结合本组2例共纳入43例。足月儿17例,早产儿26例。脑脊液白细胞、葡萄糖和蛋白水平中位数分别为566个/mm^(3)、0.2 mmol/L、2.2 g/L。27例应用脑脊液培养诊断,6例应用mNGS诊断,4例应用脑脊液培养和聚合酶链反应诊断,6例应用其他方式诊断。14例全程仅应用大环内酯类抗生素,8例大环内酯类与另一种抗生素联用,9例应用非大环内酯类抗生素,12例未予抗脲原体治疗。17例足月儿均存活,合并脑积水8例次。26例早产儿死亡8例,合并脑室周围-脑室内出血18例次,脑积水15例次。结论早产儿脲原体脑膜炎脑脊液葡萄糖水平明显降低,脑积水为常见并发症,病因不明且治疗无效的颅内感染可应用mNGS技术检测病原,单用或联合应用大环内酯类抗生素为主要治疗方式。

Objective To study the clinical features and treatment strategy of neonatal ureaplasma meningitis.Methods During 2021,the clinical data of 2 neonates with ureaplasma meningitis treated in Children's Hospital of Hunan Province were retrospectively analyzed.Literature on this subject were searched in the following databases:CNKI,Wanfang Database,Chinese Medical Journal Full-Text Database,CQVIP database,SinoMed,PubMed,Embase and Web of Science(up to March 2022).The key words included“infant”,“neonate”,“newborn”,“ureaplasma”,“mycoplasma urealytium”,“meningitis”,“central nervous system infection”,“brain”.The clinical data,treatment and prognosis of patients from the literature were summarized.Results Case 1,female,gestational age(GA)33+3 weeks,intracranial hemorrhage(ICH)and ventricular dilatation were found on 2 d after birth.The cerebrospinal fluid(CSF)routine and biochemistry tests indicated meningitis,but the CSF culture was negative.No improvement after antibiotic treatment.CSF metagenomic next-generation sequencing(mNGS)and 23S rRNA showed Ureaplasma urealyticum on 30 d after birth.The patient was treated with doxycycline(DOX)for 21 d until mNGS turned negative and DOX was discontinued.However,the disease recurred 23 d later and erythromycin was added with DOX as combined therapy.The patient was followed up until 6 months without neurodevelopmental disabilities.Case 2,male,GA 26 weeks,ICH and ventricular dilatation were found on 10 d after birth.The CSF routine and biochemistry tests indicated meningitis,but the CSF culture was negative.No improvement after antibiotic treatment.CSF mNGS and 23S rRNA showed Ureaplasma parvum.The patient received erythromycin therapy for 32 d and had normal neurodevelopment at 5 months.According to the literature,43 cases were reported including the 2 cases descirbed above,17 cases were full-term infants and 26 cases were preterm infants.The median CSF leukocytes,glucose and proteins were 566 cells/mm^(3),0.2 mmol/L and 2.2 g/L.27 cases were diagnosed based on CSF culture,6 cases using mNGS,4 cases with both CSF culture and PCR method and 6 cases with other methods.Macrolides alone were used in 14 cases,macrolides combined with another antibiotic were used in 8 cases,non-macrolide antibiotics were used in 9 cases and 12 cases didn't receive any anti-ureaplasma therapy.All 17 term infants survived,however,8 cases with hydrocephalus.Among the 26 preterm infants,8 patients died,18 patients had periventricular-intraventricular hemorrhage and 15 patients had hydrocephalus.Conclusions Neonatal ureaplasma meningitis has significantly lower CSF glucose level with hydrocephalus as the common complication.For intracranial infections of unknown etiology and no response to treatment,mNGS is helpful in determining the pathogen.Neonatal ureaplasma meningitis should be treated with macrolides alone or as add-on therapy.