A study on the clinical characteristics,strain clustering analysis and in vitro drug sensitivity of Talaromyces marneffei infection in HIV-negative patients

LIANG Liang; JIANG Jie; DUAN Wenlong; CHEN Xingchun

doi:10.3969/j.issn.1674-3806.2025.07.06

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.