Table_1_Nocardia Infection in Nephrotic Syndrome Patients: Three Case Studies and A Systematic Literature Review.docx

ObjectiveThe multicenter literature review and case studies of 3 patients were undertaken to provide an updated understanding of nocardiosis, an opportunistic bacterial infection affecting immunosuppressed nephrotic syndrome (NS) patients receiving long-term glucocorticoid and immunosuppressant treatment. The results provided clinical and microbiological data to assist physicians in managing nocardiosis patients.
MethodsThree cases between 2017 and 2018 from a single center were reported. Additionally, a systematic review of multicenter cases described in the NCBI PubMed, Web of Science, and Embase in English between January 1, 2001 and May 10, 2021 was conducted.
ResultsThis study described three cases of Nocardia infection in NS patients. The systematic literature review identified 24 cases with sufficient individual patient data. A total of 27 cases extracted from the literature review showed that most patients were > 50 years of age and 70.4% were male. Furthermore, the glucocorticoid or corticosteroid mean dose was 30.9 ± 13.7 mg per day. The average time between hormone therapy and Nocardia infection was 8.5 ± 9.7 months. Pulmonary (85.2%) and skin (44.4%) infections were the most common manifestations in NS patients, with disseminated infections in 77.8% of patients. Nodule/masses and consolidations were the major radiological manifestations. Most patients showed elevated inflammatory biomarkers levels, including white blood cell counts, neutrophils percentage, and C-reactive protein. Twenty-five patients received trimethoprim-sulfamethoxazole monotherapy (18.5%) or trimethoprim-sulfamethoxazole-based multidrug therapy (74.1%), and the remaining two patients (7.4%) received biapenem monotherapy. All patients, except the two who were lost to follow-up, survived without relapse after antibiotic therapy.
ConclusionsNephrotic syndrome patients are at high risk of Nocardia infection even if receiving low-dose glucocorticoid during the maintenance therapy. The most common manifestations of nocardiosis in NS patients include abnormal lungs revealing nodules and consolidations, skin and subcutaneous abscesses. The NS patients have a high rate of disseminated and cutaneous infections but a low mortality rate. Accurate and prompt microbiological diagnosis is critical for early treatment, besides the combination of appropriate antibiotic therapy and surgical drainage when needed for an improved prognosis.

【研究目的】本研究通过多中心文献回顾与3例患者的病例分析，旨在更新对诺卡菌病（nocardiosis）的认知——该病为一种机会性细菌感染，好发于接受长期糖皮质激素与免疫抑制剂治疗的免疫抑制型肾病综合征（NS）患者。本研究所得临床与微生物学数据，可为临床医师管理诺卡菌病患者提供参考。

【研究方法】本研究报道了单中心2017年至2018年间收治的3例病例。此外，我们系统检索了2001年1月1日至2021年5月10日期间发表于NCBI PubMed、Web of Science及Embase数据库的英文文献，对其中报道的多中心病例进行了汇总分析。

【研究结果】本研究报道了3例NS患者的诺卡菌（Nocardia）感染病例。通过系统文献回顾，共纳入24例具备完整患者个体数据的病例。综上，本次汇总的27例病例显示，多数患者年龄超过50岁，其中70.4%为男性。患者每日糖皮质激素（或皮质类固醇）平均给药剂量为30.9±13.7mg，从激素治疗至确诊诺卡菌感染的平均间隔时间为8.5±9.7个月。NS患者最常见的感染部位为肺部（85.2%）与皮肤（44.4%），77.8%的患者存在播散性感染。影像学主要表现为结节/肿块与肺实变。多数患者的炎症生物标志物水平升高，包括白细胞计数、中性粒细胞百分比及C反应蛋白（C-reactive protein）。25例患者接受了甲氧苄啶-磺胺甲噁唑（trimethoprim-sulfamethoxazole）单药治疗（18.5%）或以其为基础的联合药物治疗（74.1%），剩余2例（7.4%）接受了比阿培南（biapenem）单药治疗。除2例失访患者外，其余患者均在接受抗生素治疗后痊愈，未出现复发。

【研究结论】肾病综合征患者即便在维持治疗阶段接受低剂量糖皮质激素，仍存在较高的诺卡菌感染风险。NS患者的诺卡菌病最常见临床表现为肺部结节与实变、皮肤及皮下脓肿。该类患者播散性感染与皮肤感染的发生率较高，但总体病死率较低。及时准确的微生物学诊断是早期治疗的关键，此外，联合使用合适的抗生素治疗，并在必要时辅以外科引流，可改善患者预后。