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采用下一代测序技术诊断的小儿败血性休克合并 B 群链球菌脑膜炎病例:两例报告。

Pediatric sepsis cases diagnosed with group B streptococcal meningitis using next-generation sequencing: a report of two cases.

机构信息

Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.

Department of Human Genetics and Molecular Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

出版信息

BMC Infect Dis. 2021 Jun 5;21(1):531. doi: 10.1186/s12879-021-06231-3.

Abstract

BACKGROUND

Group B Streptococcus (GBS) is an important cause of invasive infection in neonates and infants. Cerebrospinal fluid (CSF) findings and culture may not show evidence of infection early in GBS meningitis. Next-generation sequencing (NGS) has the potential to detect microbial genetic material in patients with infectious diseases. We report two cases of infantile sepsis of GBS meningitis with negative results for CSF culture tests, but positive results for NGS analysis.

CASE PRESENTATION

Patient 1 was a 22-day-old male infant diagnosed with sepsis and meningitis. His CSF findings showed pleocytosis, decreased glucose, and increased protein levels. However, CSF and blood culture results at admission were negative. He received a total of 3 weeks of treatment with ampicillin and cefotaxime, and showed clinical improvement. GBS was detected through NGS analysis of CSF collected at admission. Patient 2 was a 51-day-old male infant with sepsis. CSF findings on admission were normal, and blood and CSF cultures were also negative. Intravenous ampicillin and cefotaxime treatment were initiated. Treatment was de-escalated to ampicillin alone because Enterococcus faecalis was cultured from urine. He was discharged after a total of 1 week of antibiotic treatment. Six days after discharge, he was re-hospitalized for sepsis. Blood and CSF cultures were negative, and E. faecalis was again cultured from urine. He received a total of 3 weeks of ampicillin treatment for enterococcal-induced nephritis and did not relapse thereafter. NGS pathogen searches were retrospectively performed on both blood and CSF collected at the first and second admission. GBS was detected in the CSF collected at the first admission, but no significant pathogen was detected in the other samples. Inadequate treatment for GBS meningitis at the first admission may have caused the recurrence of the disease.

CONCLUSION

Infantile sepsis may present bacterial meningitis that is not diagnosed by either culture testing or CSF findings. NGS analysis for CSF may be useful for confirming the diagnosis of bacterial meningitis.

摘要

背景

B 群链球菌(GBS)是导致新生儿和婴儿侵袭性感染的重要原因。在 GBS 脑膜炎早期,脑脊液(CSF)检查和培养可能无法显示感染证据。下一代测序(NGS)有可能检测出传染病患者的微生物遗传物质。我们报告了两例婴儿 GBS 脑膜炎败血症,CSF 培养检测结果为阴性,但 NGS 分析结果为阳性。

病例介绍

患者 1 为 22 天男性婴儿,诊断为败血症和脑膜炎。他的 CSF 检查显示白细胞增多、葡萄糖减少和蛋白质水平升高。然而,入院时 CSF 和血培养结果均为阴性。他接受了总共 3 周的氨苄西林和头孢噻肟治疗,临床症状改善。通过入院时采集的 CSF 进行 NGS 分析检测到 GBS。患者 2 为 51 天男性婴儿,患有败血症。入院时 CSF 检查正常,血和 CSF 培养均为阴性。开始静脉注射氨苄西林和头孢噻肟治疗。由于尿液中培养出粪肠球菌,治疗降级为仅使用氨苄西林。他总共接受了 1 周的抗生素治疗后出院。出院后 6 天,他因败血症再次住院。血和 CSF 培养均为阴性,尿液中再次培养出粪肠球菌。他总共接受了 3 周的氨苄西林治疗肠球菌性肾炎,此后未再复发。对首次和第二次入院时采集的血液和 CSF 进行了 NGS 病原体搜索。在第一次入院时采集的 CSF 中检测到 GBS,但其他样本中未检测到明显病原体。第一次入院时对 GBS 脑膜炎的治疗不充分可能导致疾病复发。

结论

婴儿败血症可能表现为细菌脑膜炎,通过培养检测或 CSF 检查均无法诊断。CSF 的 NGS 分析可能有助于确认细菌性脑膜炎的诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10cf/8180162/e225e604f9c0/12879_2021_6231_Fig1_HTML.jpg

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