Nwankwo Lisa, Gilmartin Desmond, Matharu Sheila, Nuh Ali, Donovan Jackie, Armstrong-James Darius, Shah Anand
Pharmacy Department, Royal Brompton Hospital, Guy's and St. Thomas' NHS Foundation Trust, London SW3 6NP, UK.
Clinical Informatics, Royal Brompton and Harefield Hospital Foundation NHS Trust, Fulham, London SW3 6HP, UK.
J Fungi (Basel). 2022 Mar 31;8(4):362. doi: 10.3390/jof8040362.
Background: Instances of resistant fungal infection are rising in pulmonary disease, with limited therapeutic options. Therapeutic drug monitoring of azole antifungals has been necessary to ensure safety and efficacy but is considered unnecessary for the newest triazole isavuconazole. Aims: To characterise the prevalence of isavuconazole resistance and use in a tertiary respiratory centre. Methods: A retrospective observational analysis (2016−2021) of adult respiratory patients analysing fungal culture, therapeutic drug monitoring, and outcome post-isavuconazole therapy. Results: During the study period, isavuconazole susceptibility testing was performed on 26 Aspergillus spp. isolates. A total of 80.8% of A. fumigatus isolates had isavuconazole (MIC > 1 mg/L, and 73.0% > 2 mg/L) with a good correlation to voriconazole MIC (r = 0.7, p = 0.0002). A total of 54 patients underwent isavuconazole therapy during the study period (median duration 234 days (IQR: 24−499)). A total of 67% of patients tolerated isavuconazole, despite prior azole toxicity in 61.8%, with increased age (rpb = 0.31; p = 0.021) and male sex (φc = 0.30; p = 0.027) being associated with toxicity. A total of 132 isavuconazole levels were performed with 94.8% > 1 mg/L and 72% > 2 mg/L. Dose change from manufacturer’s recommendation was, however, required in 9.3% to achieve a concentration of >2 mg/L. Conclusion: We describe the use of isavuconazole as a salvage therapy in a chronic pulmonary fungal disease setting with a high prevalence of azole resistance. Therapeutic concentrations at standard dosing were high; however, results reinforce antifungal stewardship for optimization.
肺部疾病中耐药真菌感染的病例正在增加，治疗选择有限。对唑类抗真菌药物进行治疗药物监测对于确保安全性和有效性是必要的，但对于最新的三唑类药物艾沙康唑则认为没有必要。目的：描述艾沙康唑耐药的患病率及其在三级呼吸中心的使用情况。方法：对成年呼吸患者进行回顾性观察分析（2016 - 2021年），分析真菌培养、治疗药物监测以及艾沙康唑治疗后的结果。结果：在研究期间，对26株曲霉属分离株进行了艾沙康唑药敏试验。共有80.8%的烟曲霉分离株对艾沙康唑耐药（最低抑菌浓度>1mg/L，73.0%>2mg/L），与伏立康唑最低抑菌浓度具有良好的相关性（r = 0.7，p = 0.0002）。在研究期间，共有54例患者接受了艾沙康唑治疗（中位疗程234天（四分位间距：24 - 499天））。尽管61.8%的患者先前有唑类药物毒性，但共有67%的患者耐受艾沙康唑，年龄增加（rpb = 0.31；p = 0.021）和男性（φc = 0.30；p = 0.027）与毒性相关。共进行了132次艾沙康唑血药浓度检测，94.8%>1mg/L，72%>2mg/L。然而，为达到>2mg/L的浓度，9.3%的患者需要改变制造商推荐的剂量。结论：我们描述了在唑类耐药率高的慢性肺部真菌病环境中使用艾沙康唑作为挽救治疗的情况。标准剂量下的治疗浓度较高；然而，结果加强了对抗真菌药物管理以进行优化的必要性。
