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使用严格标准合理运用微生物学检测诊断中枢神经系统感染:一项回顾性研究

Rational Use of Microbiological Tests in the Diagnosis of Central Nervous System Infections Using Restrictive Criteria: a Retrospective Study.

作者信息

Ngo Nsoga M T, Pérez-Rodriguez F J, Mamin A, L'Huillier A G, Cherkaoui A, Kaiser L, Schibler M

机构信息

Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.

Faculty of Medicine, University of Geneva, Geneva, Switzerland.

出版信息

Microbiol Spectr. 2023 Mar 27;11(2):e0317922. doi: 10.1128/spectrum.03179-22.

Abstract

Central nervous infections, mostly represented by meningitis and encephalitis, remain a diagnostic challenge despite substantial advances in microbiological tools in recent years. Meanwhile, extensive microbiological workups, which often prove to be irrelevant retrospectively, continue to be processed on a large scale, therefore leading to unnecessary costs. The main goal of this study was to evaluate a systematic approach enabling more rational use of microbiological tools in the setting of community-acquired central nervous system infection diagnosis. In this single-center descriptive study, the modified Reller criteria were retrospectively extended to all neuropathogens tested in cerebrospinal fluid (CSF) samples with the FilmArray meningitis/encephalitis panel (BioFire Diagnostics, LLC) and bacterial culture. The inclusion period was 30 months. In total, 1,714 fluid (CSF) samples analyzed from 1,665 patients over 2 and a half years were reported. According to the retrospective application of the modified Reller criteria, microbiological testing was considered unnecessary in 544 CSF samples. Fifteen positive microbiological results were found among these samples, interpreted either as inherited chromosomally integrated human herpesvirus 6 (HHV-6), a false-positive result, or a true microbial detection without clinical relevance. No CNS infection case would have been missed if these analyses were not carried out, while about one-third of all meningitis/encephalitis multiplex PCR panels would have been saved. Our retrospective analysis suggests that the modified Reller criteria could be safely applied to all microbiological tests performed in CSF, thereby saving substantial costs. Microbiological testing in general and in the setting of central nervous system (CNS) infection in particular are often excessive, leading to superfluous laboratory work and costs. In this regard, restrictive criteria, named Reller criteria, have been developed to reduce unnecessary CSF herpes simplex virus 1 (HSV-1) PCR testing when suspecting encephalitis. These criteria were then adapted for increased safety to become the modified Reller criteria. This retrospective study aims at evaluating the safety of these criteria when applied to CSF microbiological testing in general, including multiplex PCR, direct examination, and bacterial culture. The postulate was that a CNS infection can be excluded if none of these criteria is present. According to our data set, no CNS infection would have been missed if the modified Reller criteria would have been applied to save microbiological tests. This study therefore proposes a simple way to reduce unnecessary microbiological testing in the context of CNS infection suspicion.

摘要

尽管近年来微生物检测手段取得了显著进展,但以脑膜炎和脑炎为主要表现的中枢神经系统感染仍是一个诊断难题。与此同时,大量微生物检查在回顾时往往被证明是无关紧要的,但仍在大规模进行,从而导致不必要的费用。本研究的主要目的是评估一种系统方法,以便在社区获得性中枢神经系统感染诊断中更合理地使用微生物检测手段。在这项单中心描述性研究中,将改良的雷勒标准回顾性地扩展应用于所有通过FilmArray脑膜炎/脑炎检测板(BioFire诊断公司)和细菌培养对脑脊液(CSF)样本中检测的神经病原体。纳入期为30个月。在两年半的时间里,共报告了对1665例患者分析的1714份脑脊液样本。根据改良雷勒标准的回顾性应用,544份脑脊液样本被认为无需进行微生物检测。在这些样本中发现了15个阳性微生物检测结果,这些结果要么被解释为遗传性染色体整合的人类疱疹病毒6型(HHV-6),属于假阳性结果,要么是无临床相关性的真正微生物检测。如果不进行这些分析,不会漏诊任何中枢神经系统感染病例,同时大约三分之一的脑膜炎/脑炎多重PCR检测板可以节省下来。我们的回顾性分析表明,改良的雷勒标准可以安全地应用于所有脑脊液微生物检测,从而节省大量费用。一般的微生物检测,特别是中枢神经系统(CNS)感染情况下的检测,往往过度,导致多余的实验室工作和费用。在这方面,已制定了名为雷勒标准的限制性标准,以减少在怀疑脑炎时不必要的脑脊液单纯疱疹病毒1型(HSV-1)PCR检测。这些标准随后为提高安全性而进行了调整,成为改良的雷勒标准。这项回顾性研究旨在评估这些标准在一般脑脊液微生物检测(包括多重PCR、直接检查和细菌培养)中的安全性。假设是如果不存在这些标准中的任何一条,就可以排除中枢神经系统感染。根据我们的数据集,如果应用改良的雷勒标准来节省微生物检测,不会漏诊任何中枢神经系统感染病例。因此,本研究提出了一种在怀疑中枢神经系统感染时减少不必要微生物检测的简单方法。

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