Department of Infectious Diseases, Leiden University Medical Center, 2333ZA Leiden, the Netherlands.
Department of Clinical Epidemiology, Leiden University Medical Center, 2333ZA Leiden, the Netherlands.
Med Mycol. 2021 Dec 8;60(1). doi: 10.1093/mmy/myab060.
World-wide, emerging triazole resistance increasingly complicates treatment of invasive aspergillosis (IA). In settings with substantial (>10%) prevalence of triazole resistance, empiric combination therapy with both a triazole and liposomal amphotericin B (LAmB) can be considered because of the low yields of susceptibility testing. To avoid toxicity while optimizing outcome, a strategy with monotherapy would be preferable. A newly designed treatment algorithm based on literature and expert consensus provided guidance for empiric monotherapy with either voriconazole or LAmB. Over a four and a half year period, all adult patients in our hospital treated for IA were included and patient data were collected. An independent committee reviewed the attributability of death to IA for each patient. Primary outcomes were 30- and 100-day crude mortality and attributable mortality. In total, 110 patients were treated according to the treatment algorithm. Fifty-six patients (51%) were initially treated with voriconazole and 54 patients (49%) with LAmB. Combined attributable and contributable mortality was 13% within 30 days and 20% within 100 days. Treatment switch to LAmB was made in 24/56 (43%) of patients who were initially treated with voriconazole. Combined contributable and attributable 100-day mortality in this subgroup was 21% and was not increased when compared with patients initially treated with LAmB (P = 0.38). By applying a comprehensive clinical decision algorithm, an antifungal-sparing regime was successfully introduced. Further research is warranted to explore antifungal treatment strategies that account for triazole-resistance.
Due to resistance of Aspergillus against triazoles, combination therapy with liposomal amphotericin B (LAmB) is applied more often as primary therapy against invasive aspergillosis. This study presents the results of a decision tool which differentiated between triazole or LAmB monotherapy.
在全球范围内，不断出现的三唑类耐药性使侵袭性曲霉病（IA）的治疗变得越来越复杂。在耐药率较高（>10%）的地区，由于药敏试验的结果不可靠，经验性联合治疗方案，即三唑类药物联合两性霉素 B 脂质体（LAmB）可以被考虑。为了避免毒性，同时优化治疗结果，采用单药治疗的策略会更好。根据文献和专家共识设计的新治疗方案为伏立康唑或 LAmB 的经验性单药治疗提供了指导。在四年半的时间里，我院所有接受 IA 治疗的成年患者都被纳入并收集了患者数据。一个独立的委员会审查了每位患者的死亡归因于 IA 的情况。主要结局为 30 天和 100 天的粗死亡率和归因死亡率。根据治疗方案，共治疗了 110 例患者。56 例（51%）患者最初接受伏立康唑治疗，54 例（49%）患者接受 LAmB 治疗。30 天内的联合归因和贡献死亡率为 13%，100 天内的联合归因和贡献死亡率为 20%。在最初接受伏立康唑治疗的 56 例患者中，有 24 例（43%）患者转为 LAmB 治疗。该亚组的 100 天联合归因和贡献死亡率为 21%，与最初接受 LAmB 治疗的患者相比并未增加（P=0.38）。通过应用全面的临床决策算法，成功引入了抗真菌药物节约方案。进一步的研究是必要的，以探索考虑三唑类耐药性的抗真菌治疗策略。
由于曲霉菌对三唑类药物的耐药性，侵袭性曲霉病的一线治疗更多地采用两性霉素 B 脂质体（LAmB）联合治疗。本研究介绍了一种决策工具的结果，该工具区分了三唑类或 LAmB 单药治疗。
