Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
Clin Infect Dis. 2021 Dec 6;73(11):e3727-e3732. doi: 10.1093/cid/ciaa1555.
Itraconazole is the preferred azole for histoplasmosis in the current Infectious Diseases Society of America guidelines. Voriconazole is increasingly used as treatment for histoplasmosis; it has in vitro activity against Histoplasma capsulatum and has shown success in case reports and small case series, but may have a lower barrier to resistance. No comparative studies have been published.
We constructed a single-center, retrospective cohort of adult patients diagnosed with histoplasmosis from 2002 to 2017. Individual charts were reviewed to gather clinical information, including demographics, clinical features, immune status, treatments, and mortality. Patients were categorized based on the choice of azole and use as an initial treatment or as a step-down therapy from amphotericin B. Initial therapies with other azoles were excluded. Mortality was compared using a multivariable Cox proportional hazards with Heaviside function at 42 days.
We identified 261 cases of histoplasmosis from 2002 to 2017. After excluding patients not treated with itraconazole or voriconazole, 194 patients remained. Of these, 175 (90%) patients received itraconazole and 19 (10%) received voriconazole. There were no significant demographic differences between patient populations receiving either azole as their initial azole treatment. Death at 180 days occurred in 41 patients (23.4%) in the itraconazole group and 6 patients (31.6%) in the voriconazole group. Patients on voriconazole had a statistically significant increase in mortality during the first 42 days after initiation of treatment when compared to patients receiving itraconazole (hazard ratio, 4.30; 95% confidence interval, 1.3-13.9; P = .015), when controlled for other risk factors.
Voriconazole in histoplasmosis was associated with increased mortality in the first 42 days when compared to itraconazole.
依曲康唑是当前美国传染病学会指南中治疗组织胞浆菌病的首选唑类药物。伏立康唑越来越多地被用于治疗组织胞浆菌病；它对荚膜组织胞浆菌具有体外活性，并在病例报告和小病例系列中取得了成功，但可能具有更低的耐药性障碍。目前尚未发表比较研究。
我们构建了一个 2002 年至 2017 年期间在单一中心确诊为组织胞浆菌病的成年患者的回顾性队列。查阅个人图表以收集临床信息，包括人口统计学、临床特征、免疫状态、治疗方法和死亡率。根据唑类药物的选择以及作为初始治疗或两性霉素 B 降阶梯治疗对患者进行分类。排除初始使用其他唑类药物的患者。使用 42 天的 Heaviside 函数的多变量 Cox 比例风险进行死亡率比较。
我们从 2002 年至 2017 年期间确定了 261 例组织胞浆菌病病例。排除未接受伊曲康唑或伏立康唑治疗的患者后，剩余 194 例。其中，175 例（90%）患者接受伊曲康唑治疗，19 例（10%）患者接受伏立康唑治疗。接受伊曲康唑或伏立康唑作为初始唑类药物治疗的患者人群之间没有明显的人口统计学差异。伊曲康唑组 180 天死亡 41 例（23.4%），伏立康唑组 6 例（31.6%）。与接受伊曲康唑治疗的患者相比，在开始治疗后的前 42 天，接受伏立康唑治疗的患者死亡率显著增加（风险比，4.30；95%置信区间，1.3-13.9；P =.015），当控制其他危险因素时。
与伊曲康唑相比，伏立康唑在组织胞浆菌病中的应用与前 42 天的死亡率增加相关。
