The delayed clearance of Talaromyces marneffei in blood culture may be associated with higher MIC of voriconazole after antifungal therapy among AIDS patients with talaromycosis

PLOS NEGLECTED TROPICAL DISEASES(2023)

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摘要
ObjectivesThis study aimed to investigate the influencing factors of delayed clearance of Talaromyces marneffei (T. marneffei) in blood culture of patients with acquired immune deficiency syndrome (AIDS) complicated with talaromycosis after antifungal therapy. MethodsThe patients with AIDS complicated with talaromycosis were retrospectively enrolled, and divided into two groups according to the blood T. marneffei culture results in two weeks after antifungal therapy. The baseline clinical data were collected and the antifungal susceptibility of T. marneffei was tested. ResultsA total of 190 patients with AIDS and talaromycosis were enrolled, of whom 101 cases remained positive for T. marneffei (Pos-group) while the other 89 cases were negative in blood culture (Neg-group) after two weeks' antifungal treatment. The Pos-group had a higher baseline Aspartate aminotransferase (AST, 78.5 vs. 105 U/L; P = 0.073) and lower CD4+ T cells level (11 vs. 7 cells/mu l; P = 0.061). The percentage of isolates with higher MICs of voriconazole (VOR) and fluconazole (FLU) in the Pos-group were significantly higher than those in the Neg-group (chi(2) = 12.623, P < 0.001 and chi(2) = 9.356, P = 0.002, respectively). By multivariate logistic regression, the MIC value for VOR was identified as the prognostic variable that may influence the clearance of T. marneffei in blood culture after antifungal therapy among AIDS patients with talaromycosis. ConclusionsThe delayed negative conversion of blood T. marneffei-culture may be associated with some factors especially higher MIC of VOR, indicatingthe possibility of drug resistance of T. marneffei. Author summarySlow fungal clearance after antifungal therapy was observed in a few talaromycosis Marneffei (TSM) patients, leading to a significant prolongation of hospital day and increasing adverse drug reaction. The reasons of delayed clearance of Talaromyces Marneffei(T. marneffei) is still unclear. Although no standard cutoff value about minimum inhibitory concentration (MIC), the drug sensitivity results are still used to guide the clinical practice. Several studies had reported the MIC value of T. marneffei isolates against echinocandin, amphotericin B, and azoles in vitro in the past decade. Patients who infected with azole-resistant strains had a higher mortality risk than those infected with susceptible strains. To response to this phenomenon, the authors hypothesized that the susceptibility of T. marneffei strains to antifungal agents could affect its clearance in blood, and verifications were performed in the study.
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关键词
antifungal therapy,talaromyces marneffei,voriconazole,aids patients
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