| 摘要: |
| ［摘要］ 目的 探究人类免疫缺陷病毒（HIV）阴性者马尔尼菲篮状菌（Tm）感染的临床特征、菌株亲缘聚类关系及9种抗真菌药物对Tm体外酵母相的最低抑菌浓度（MIC）。方法 分析2020年1月至2025年5月广西壮族自治区人民医院收治的32例HIV阴性的Tm感染患者的临床资料，应用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）鉴定菌株及聚类分析，用微量肉汤稀释法检测MIC。结果 标本来源以血液（50.00%）和气管吸取物（15.63%）为主。患者中位年龄59岁，基础疾病以糖尿病（28.13%）和慢性乙型肝炎（21.88%）为主；主要表现为发热（71.88%）和呼吸系统症状（68.75%）。外周血白细胞计数中位值为18.2×109/L，C反应蛋白（CRP）中位值为154.3 mg/L，真菌（1，3）-β-D-葡聚糖试验阳性率为81.25%。抗干扰素-γ自身抗体检测阳性率为25.00%。MALDI-TOF MS鉴定Tm平均得分为（2.07±0.09）分，与形态学鉴定结果总符合率达100.00%，聚类分属两大簇。药敏试验结果显示，伏立康唑、艾沙康唑、伊曲康唑、泊沙康唑、5-氟胞嘧啶、两性霉素B、氟康唑、卡泊芬净、米卡芬净的抑制90%微生物生长所需的MIC（MIC90）依次为≤0.015、≤0.015、0.12、0.12、0.25、1.00、4.00、4.00、≥8.00 μg/mL。结论 HIV阴性的Tm感染多见于中老年免疫抑制人群，临床表现缺乏特异性。炎症标志物联合真菌葡聚糖检测利于早期诊断，应加强Tm感染患者自身免疫抗体筛查。MALDI-TOF MS可快速鉴定Tm并进行聚类分析。两性霉素B、伊曲康唑和伏立康唑可作为经验性治疗首选药物。 |
| 关键词: 人类免疫缺陷病毒阴性 马尔尼菲篮状菌 临床特征 基质辅助激光解吸电离飞行时间质谱 聚类分析 最低抑菌浓度 |
| DOI：10.3969/j.issn.1674-3806.2025.07.06 |
| 分类号:R 519 |
| 基金项目: |
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| A study on the clinical characteristics, strain clustering analysis and in vitro drug sensitivity of Talaromyces marneffei infection in HIV-negative patients |
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LIANG Liang1, JIANG Jie1, DUAN Wenlong2, CHEN Xingchun1
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1.Department of Laboratory Medicine, the People′s Hospital of Guangxi Zhuang Autonomous Region(Guangxi Academy of Medical Sciences), Nanning 530021, China; 2.Department of Emergency, the People′s Hospital of Guangxi Zhuang Autonomous Region(Guangxi Academy of Medical Sciences), Nanning 530021, China
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| Abstract: |
| ［Abstract］ Objective To explore the clinical characteristics, strain phylogenetic clustering relationships, and the minimum inhibitory concentration(MIC) of 9 antifungal drugs against the yeast phase of Talaromyces marneffei(Tm) in vitro in HIV-negative patients with Tm infection. Methods The clinical data of 32 HIV-negative patients with Tm infection who were admitted to the People′s Hospital of Guangxi Zhuang Autonomous Region between January 2020 and May 2025 were analyzed. Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS) was used for strain identification and clustering analysis. The broth microdilution method was employed to detect the MIC. Results The sources of the specimens were mainly blood(50.00%) and tracheal aspirates(15.63%). The median age of the patients was 59 years old. The underlying diseases were mainly diabetes(28.13%) and chronic hepatitis B(21.88%), and the patients′ main manifestations were fever(71.88%) and respiratory symptoms(68.75%). The median value of white blood cell count in the peripheral blood of the patients was 18.2×109/L, and the median value of C-reactive protein(CRP) was 154.3 mg/L. The positive rate of fungal beta-1, 3-glucan test was 81.25%. The positive rate of anti-interferon-γ autoantibody detection was 25.00%. The average scores for identifying Tm by using MALDI-TOF MS were (2.07±0.09)points, and the total consistency rate between the results of identifying Tm by using MALDI-TOF MS and the results of identifying Tm by using morphology reached 100.00%. The clustering analysis showed that the strains belonged to two major clusters. The results of the drug sensitivity test showed that the minimum inhibitory concentration required to inhibit the growth of 90% of organisms(MIC90) values of voriconazole, isavuconazole, itraconazole, posaconazole, 5-flucytosine, amphotericin B, fluconazole, caspofungin and micafungin were ≤0.015, ≤0.015, 0.12, 0.12, 0.25, 1.00, 4.00, 4.00 and ≥8.00 μg/mL, respectively. Conclusion HIV-negative patients with Tm infection are more common in middle-aged and elderly immunosuppressed populations, and their clinical manifestations lack specificity. The combined detection of inflammatory markers and fungal beta-1, 3-glucan is conducive to early diagnosis. Screening for autoimmune antibodies in Tm infection patients should be strengthened. MALDI-TOF MS can be used for rapidly identifying Tm and clustering analysis. Amphotericin B, itraconazole and voriconazole can be used as the first choice of drugs for empirical treatment. |
| Key words: Human immunodeficiency virus(HIV) negative Talaromyces marneffei(Tm) Clinical characteristics Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS) Clustering analysis Minimum inhibitory concentration(MIC) |
