Jiang Zhiwen, Song Cong, Li Bingkun, Li Xiuying, Yu Xiaoshu, Zhou Siru, Li Tiantian, Huang Qihua, Mo Nanfang, He Xiaojuan, Pang Qian, Yao Zhijian, Zhou Changjing, Cao Cunwei
Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
Guangxi Key Laboratory of Mycosis Prevention and Treatment, Nanning, 530021, China.
Mycopathologia. 2025 Feb 5;190(1):24. doi: 10.1007/s11046-024-00915-5.
Voriconazole (VRC) has been used as an alternative treatment for talaromycosis. However, there are few studies reporting the VRC plasma concentration in patients with talaromycosis. The purpose of this study was to analyze the correlations between VRC initial steady-state trough concentration and clinical outcomes.
We prospectively enrolled patients who were diagnosed with talaromycosis and received VRC as initial antifungal treatment regime. Medical information, VRC initial steady-state trough concentration, clinical outcomes and adverse events (AEs) were recorded for analysis.
This study included 69 patients with talaromycosis receiving VRC treatment, including 38 HIV-positive patients and 31 HIV-negative patients. The average age of the HIV-positive patients was 42 years, and that of the HIV-negative patients was 51 years. After 12 weeks of antifungal treatment, 55 patients achieved clinical remission, 3 patients were transferred to amphotericin B treatment because of persistent clinical symptoms, and 5 patients died, 2 patients discontinued VRC treatment due to AEs. Follow up to 6 months, a total of 14 AEs were observed in 12 patients, and 3 patients discontinued VRC treatment due to AEs. The average VRC initial steady-state trough concentration was 5.26 mg/L, with a range of 0.23-16.95 mg/L, indicating high variability. No correlation was found between the VRC initial steady-state trough concentration and treatment failure (P = 0.079). A significant correlation between AEs and the VRC initial steady-state trough concentration was found (P = 0.048). The VRC initial steady-state trough concentration threshold for AEs was 5.88 mg/L according to the ROC curve analysis. In addition, there was a significant correlation between mortality and the APACHE II score (P = 0.029). The risk of death significantly increased when the APACHE II score was > 10.
Voriconazole is an effective antifungal drug for talaromycosis in patients with APACHE II scores < 10. VRC steady-state trough concentration may not be significantly correlated with poor prognosis. A high VRC trough concentration was significantly correlated with AEs, and it may promote the management of AEs.
伏立康唑（VRC）已被用作治疗足分支霉病的替代疗法。然而，鲜有研究报道足分支霉病患者的伏立康唑血药浓度。本研究旨在分析伏立康唑初始稳态谷浓度与临床结局之间的相关性。
我们前瞻性纳入了被诊断为足分支霉病并接受伏立康唑作为初始抗真菌治疗方案的患者。记录患者的医疗信息、伏立康唑初始稳态谷浓度、临床结局和不良事件（AE）以进行分析。
本研究纳入了69例接受伏立康唑治疗的足分支霉病患者，其中38例为HIV阳性患者，31例为HIV阴性患者。HIV阳性患者的平均年龄为42岁，HIV阴性患者的平均年龄为51岁。抗真菌治疗12周后，55例患者实现临床缓解，3例患者因临床症状持续而改用两性霉素B治疗，5例患者死亡，2例患者因不良事件停用伏立康唑治疗。随访至6个月，12例患者共出现14次不良事件，3例患者因不良事件停用伏立康唑治疗。伏立康唑初始稳态谷浓度平均为5.26mg/L，范围为0.23 - 16.95mg/L，表明变异性较高。未发现伏立康唑初始稳态谷浓度与治疗失败之间存在相关性（P = 0.079）。发现不良事件与伏立康唑初始稳态谷浓度之间存在显著相关性（P = 0.048）。根据ROC曲线分析，不良事件的伏立康唑初始稳态谷浓度阈值为5.88mg/L。此外，死亡率与急性生理与慢性健康状况评分系统II（APACHE II）评分之间存在显著相关性（P = 0.029）。当APACHE II评分>10分时，死亡风险显著增加。
伏立康唑是治疗APACHE II评分<10分的足分支霉病患者的有效抗真菌药物。伏立康唑稳态谷浓度可能与预后不良无显著相关性。伏立康唑谷浓度较高与不良事件显著相关，这可能有助于不良事件的管理。
