Supplementary Material for: Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases

Background: The clinical spectrum of systemic nocardiosis encompasses pulmonary and disseminated disease. Central nervous system (CNS) involvement is an important feature of disseminated disease with significant mortality and high relapse rate, especially in those with suppressed cell-mediated immunity. This systematic review aimed to evaluate the epidemiology, clinical features, diagnosis, therapeutic interventions, and outcome in patients with CNS nocardiosis. Methods: A literature search was performed in major databases (PubMed, Google Scholar, and Scopus) by using distinct keywords: “CNS disease,” “Nocardia,” “meningitis,” “brain abscess,” “disseminated disease,” and “Cotrimoxazole.” We included all patients ≥18 years with CNS nocardiosis reported between January 2000 and December 2020. Results: A total of 129 papers were included in the final analysis. The mean age of patients was 55 ± 16 years, and the majority were male (70.8%). Nocardia farcinica was the commonest species (39.6%), followed by Nocardia nova (5.9%). Thirty-four percent of the patients were found to be immunocompetent. Corticosteroid use was the most common predisposing factor (55.8%). Among neuroimaging findings, brain abscess was most common (86.9%), followed by leptomeningeal enhancement (12.1%). The overall case-fatality rate in CNS disease was 22.8%. On multivariate analysis, patients who underwent surgery (OR 2.4, 95% CI 0.99–4.11, p value 0.046) had better survival than those treated with antimicrobial therapy alone. Immunodeficient state (OR 0.32, 95% CI 0.15–0.90, p value 0.019) was independently associated with poor outcome. Conclusion: CNS nocardiosis carries significant mortality, especially in immunodeficient patients. We advocate the use of surgery combined with antimicrobials to improve clinical outcome.

背景：系统性诺卡菌病的临床谱涵盖肺部感染与播散性感染。中枢神经系统（CNS）受累是播散性诺卡菌病的重要特征，可导致显著病死率与高复发率，尤以细胞免疫功能受抑人群为甚。本系统综述旨在评估中枢神经系统诺卡菌病患者的流行病学特征、临床表现、诊断方案、治疗干预手段及预后。

研究方法：于PubMed、Google Scholar及Scopus等主流数据库中开展文献检索，检索关键词包括：“中枢神经系统疾病”“诺卡菌属”“脑膜炎”“脑脓肿”“播散性疾病”及“复方新诺明（Cotrimoxazole）”。纳入2000年1月至2020年12月期间报道的所有年龄≥18岁的中枢神经系统诺卡菌病患者。

研究结果：最终共纳入129篇文献进行分析。患者平均年龄为55±16岁，多数为男性（70.8%）。最常见的致病菌为星形诺卡菌（Nocardia farcinica，39.6%），其次为新星诺卡菌（Nocardia nova，5.9%）。34%的患者免疫功能正常。应用糖皮质激素为最常见的易感危险因素（55.8%）。神经影像学表现中，脑脓肿最为多见（86.9%），其次为软脑膜强化（12.1%）。中枢神经系统诺卡菌病的总体病死率为22.8%。多因素分析显示，接受手术治疗的患者（优势比[OR] 2.4，95%置信区间[CI] 0.99~4.11，P=0.046）较仅接受抗菌药物治疗的患者生存率更佳。免疫缺陷状态（优势比[OR] 0.32，95%置信区间[CI] 0.15~0.90，P=0.019）与不良预后独立相关。

结论：中枢神经系统诺卡菌病病死率较高，尤其在免疫缺陷患者中更为显著。本研究建议采用手术联合抗菌药物的治疗方案以改善临床预后。