Consensus recommendations for the clinical application of isavuconazole(2023)
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摘要: 随着免疫抑制患者数量的增加，侵袭性霉菌感染的发病率也呈上升趋势，且患者常伴随高死亡率和临床预后不佳。艾沙康唑是权威指南推荐治疗侵袭性曲霉病和侵袭性毛霉病的一线药物，并兼顾较好的耐受性，同时具有线性药代动力学特性和与免疫抑制剂更小的药物相互作用，为长期接受免疫抑制剂治疗的患者提供了较稳定的药物浓度。Ⅲ期临床试验和病例对照研究分别证实艾沙康唑具有与伏立康唑治疗侵袭性曲霉病及两性霉素B治疗侵袭性毛霉病相似的临床疗效，并具有较好的安全性。临床研究同时也证实其在侵袭性真菌病高危人群的预防和侵袭性念珠菌病的序贯治疗中具有潜在的应用价值。本共识综合已发表的临床研究和药代动力学/药效学数据，对该药物在临床应用中的15个常见问题给予建议。Abstract: With a growing population of immunocompromised hosts, incidence of invasive mold infection is increasing, leading to a high mortality and poor clinical outcomes. Isavuconazole is the first-line drug recommended for the treatment of invasive aspergillosis(IA) and invasive mucormycosis(IM), along with its linear pharmacokinetic properties and less drug interaction with immunosuppressive agents, providing a more stable drug concentration for patients receiving long-term immunosuppressants. A phase Ⅲ trial and a case-control study demonstrated that isavuconazole showed similar clinical efficacy to voriconazole(IA treatment) and amphotericin B(IM treatment), respectively. Clinical studies have also confirmed its potential value in invasive fungal disease prophylactic treatment and oral sequential therapy of invasive candidiasis. This consensus synthesizes published clinical studies and pharmacokinetic/pharmacodynamic data to give recommendations for 15 common questions of the drug in clinical practice.
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表 2 P450 3A4代谢通路免疫抑制药物与三唑类药物联合应用对AUC的影响
三唑类治疗药物联合应用下AUC改变 VOR POS ISA 环孢素 AUC 0-τ 2倍↑# AUC 0-τ < 2倍↑# AUC 0-∞ < 2倍↑* 他克莫司 AUC 0-τ 3倍↑* AUC 0-τ 4-5倍↑* AUC 0-∞ 2倍↑* 西罗莫司 AUC 11倍↑* AUC 9倍↑* AUC 0-∞ 2倍↑* #联合应用下免疫抑制剂AUC升高≥3倍；*联合应用下免疫抑制剂AUC升高≤2倍。 
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[1] Li Z, Li Y, Chen Y, et al. Trends of pulmonary fungal infections from 2013 to 2019: an AI-based real-world observational study in Guangzhou, China[J]. Emerg Microbes Infect, 2021, 10(1): 450-460. doi: 10.1080/22221751.2021.1894902
[2] Seagle EE, Williams SL, Chiller TM. Recent Trends in the Epidemiology of Fungal Infections[J]. Infect Dis Clin N Am, 2021, 35(2): 237-260. doi: 10.1016/j.idc.2021.03.001
[3] Bitar D, Lortholary O, Le Strat Y, et al. Population-based analysis of invasive fungal infections, France, 2001-2010[J]. Emerg Infect Dis, 2014, 20(7): 1149-1155. doi: 10.3201/eid2007.131869
[4] Firacative C. Invasive fungal disease in humans: are we aware of the real impact?[J]. Mem Inst Oswaldo Cruz, 2020, 115: e200430. doi: 10.1590/0074-02760200430
[5] Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium[J]. Lancet Infect Dis, 2019, 19(12): e405-e421. doi: 10.1016/S1473-3099(19)30312-3
[6] Ananda-Rajah MR, Kontoyiannis D. Isavuconazole: a new extended spectrum triazole for invasive mold diseases[J]. Future Microbiol, 2015, 10(5): 693-708. doi: 10.2217/fmb.15.34
[7] Ellsworth M, Ostrosky-Zeichner L. Isavuconazole: Mechanism of Action, Clinical Efficacy, and Resistance[J]. J Fungi(Basel), 2020, 6(4): 324.
[8] 2022年01月05日药品批准证明文件待领取信息发布[EB/OL].
https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20220105143701157.html .[9] 范洪伟, 译. 桑福德指南抗微生物治疗指南[M]. 50版. 北京: 中国协和医科大学出版社, 2021: 86-86.
[10] Andes D, Kovanda L, Desai A, et al. Isavuconazole Concentration in Real-World Practice: Consistency with Results from Clinical Trials[J]. Antimicrob Agents Chemother, 2018, 62(7): e00585-18.
[11] Kovanda LL, Desai AV, Lu Q, et al. Isavuconazole population pharmacokinetic analysis using nonparametric estimation in patients with invasive fungal disease(results from the VITAL study)[J]. Antimicrob Agents Chemother, 2016, 60(8): 4568-4576. doi: 10.1128/AAC.00514-16
[12] Cojutti PG, Carnelutti A, Lazzarotto D, et al. Population Pharmacokinetics and Pharmacodynamic Target Attainment of Isavuconazole against Aspergillus fumigatus and Aspergillus flavus in Adult Patients with Invasive Fungal Diseases: Should Therapeutic Drug Monitoring for Isavuconazole Be Considered as Mandatory as for the Other Mold-Active Azoles?[J]. Pharmaceutics, 2021, 13(12): 2099. doi: 10.3390/pharmaceutics13122099
[13] Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients[J]. Haematologica, 2017, 102(3): 433-444. doi: 10.3324/haematol.2016.152900
[14] Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline[J]. Clin Microbiol Infect, 2018, 24 Suppl 1: e1-e38.
[15] Lewis RE. Managing drug interactions in the patient with aspergillosis[J]. Med Mycol, 2006, 44(Supplement_1): S349-S356.
[16] Groll AH, Townsend R, Desai A, et al. Drug-drug interactions between triazole antifungal agents used to treat invasive aspergillosis and immunosuppressants metabolized by cytochrome P450 3A4[J]. Transpl Infect Dis, 2017, 19(5). doi: 10.1111/tid.12751. Epub 2017 Sep 28.
[17] Fernández-Ruiz M, Bodro M, Gutiérrez Martín I, et al. Isavuconazole for the Treatment of Invasive Mold Disease in Solid Organ Transplant Recipients: A Multicenter Study on Efficacy and Safety in Real-life Clinical Practice[J]. Transplantation, 2023, 107(3): 762-773. doi: 10.1097/TP.0000000000004312
[18] EUCAST the Clinical Breakpoints, Version 10.0.2020[EB/OL]. Available online:
http://www.eucast.org (links updated Sept 2020).[19] Jing R, Morrissey I, Xiao M, et al. In vitro Activity of Isavuconazole and Comparators Against Clinical Isolates of Molds from a Multicenter Study in China[J]. Infect Drug Resist, 2022, 15: 2101-2113. doi: 10.2147/IDR.S360191
[20] Meis JF, Chowdhary A, Rhodes JL, et al. Clinical implications of globally emerging azole resistance in Aspergillus fumigatus[J]. Philos Trans R Soc Lond B Biol Sci, 2016, 371(1709): 20150460. doi: 10.1098/rstb.2015.0460
[21] Maertens JA, Raad Ⅱ, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi(SECURE): a phase 3, randomised-controlled, non-inferiority trial[J]. Lancet, 2016, 387(10020): 760-769. doi: 10.1016/S0140-6736(15)01159-9
[22] Zhang T, Shen Y, Feng S. Clinical research advances of isavuconazole in the treatment of invasive fungal diseases[J]. Front Cell Infect Microbiol, 2022, 12: 1049959. doi: 10.3389/fcimb.2022.1049959
[23] Dagher H, Hachem R, Chaftari A, et al. Real-World Use of Isavuconazole as Primary Therapy for Invasive Fungal Infections in High-Risk Patients with Hematologic Malignancy or Stem Cell Transplant[J]. J Fungi(Basel), 2022, 8(1): 74.
[24] Hassouna H, Athans V, Brizendine KD. Real-world use-Isavuconazole at a large academic medical center[J]. Mycoses, 2019, 62(6): 534-541. doi: 10.1111/myc.12910
[25] Cornely OA, Maertens J, Bresnik M, et al. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing(AmBiLoad trial)[J]. Clin Infect Dis, 2007, 44(10): 1289-1297. doi: 10.1086/514341
[26] Marty FM, Cornely OA, Mullane KM, et al. Isavuconazole for treatment of invasive fungal diseases caused by more than one fungal species[J]. Mycoses, 2018, 61(7): 485-497. doi: 10.1111/myc.12777
[27] Gebremariam T, Gu Y, Singh S, et al. Combination treatment of liposomal amphotericin B and isavuconazole is synergistic in treating experimental mucormycosis[J]. J Antimicrob Chemother, 2021, 76(10): 2636-2639. doi: 10.1093/jac/dkab233
[28] Marcos-Zambrano LJ, Gómez A, Sánchez-Carrillo C, et al. Isavuconazole is highly active in vitro against Candida species isolates but shows trailing effect[J]. Clin Microbiol Infect, 2020, 26(11): 1589-1592. doi: 10.1016/j.cmi.2020.07.023
[29] Kullberg BJ, Viscoli C, Pappas PG, et al. Isavuconazole versus caspofungin in the treatment of candidemia and other invasive candida infections: The active trial[J]. Clin Infect Dis, 2019, 68(12): 1981-1989. doi: 10.1093/cid/ciy827
[30] Caballero U, Kim S, Eraso E, et al. In Vitro Synergistic Interactions of Isavuconazole and Echinocandins against Candida auris[J]. Antibiotics(Basel), 2021, 10(4): 355.
[31] Bayona J, Palop N, García C, et al. Characteristics and Management of Candidaemia Episodes in an Established Candida auris Outbreak[J]. Antibiotics, 2020, 9: 558. doi: 10.3390/antibiotics9090558
[32] Thompson GR 3rd, Wiederhold NP. Isavuconazole: a comprehensive review of spectrum of activity of a new triazole[J]. Mycopathologia, 2010, 170(5): 291-313. doi: 10.1007/s11046-010-9324-3
[33] Nett JE, Andes DR. Antifungal Agents: Spectrum of Activity, Pharmacology, and Clinical Indications[J]. Infect Dis Clin North Am, 2016, 30(1): 51-83. doi: 10.1016/j.idc.2015.10.012
[34] Cornely OA, Mullane KM, Ostrosky-Zeichner L, et al. Isavuconazole for treatment of rare invasive fungal diseases[J]. Mycoses, 2018, 61(8): 518-533. doi: 10.1111/myc.12778
[35] Castro-Lainez MT, Sierra-Hoffman M, LLompart-Zeno J, et al. Talaromyces marneffei infection in a non-HIV non-endemic population[J]. IDCases, 2018, 12: 21-24. doi: 10.1016/j.idcr.2018.02.013
[36] Hoenigl M, Salmanton-García J, Walsh TJ, et al. Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology[J]. Lancet Infect Dis, 2021, 21(8): e246-e257. doi: 10.1016/S1473-3099(20)30784-2
[37] Schmitt-Hoffmann AH, Kato K, Townsend R, et al. Tissue distribution and elimination of isavuconazole following single and repeat oral-dose administration of isavuconazonium sulfate to rats[J]. Antimicrob Agents Chemother, 2017, 61(12): e01292-17.
[38] Lamoth F, Mercier T, André P, et al. Isavuconazole brain penetration in cerebral aspergillosis[J]. J Antimicrob Chemother, 2019, 74(6): 1751-1753. doi: 10.1093/jac/dkz050
[39] Dadwal SS, Hohl T, Fisher C, et al. American Society of Transplantation and Cellular Therapy Series, 2: Management and Prevention of Aspergillosis in Hematopoietic Cell Transplantation Recipients[J]. Transplant Cell Ther, 2021, 27(3): 201-211. doi: 10.1016/j.jtct.2020.10.003
[40] Stern A, Su Y, Lee YJ, et al. A single-center, open-label trial of isavuconazole prophylaxis against invasive fungal infection in patients undergoing allogeneic hematopoietic cell transplantation[J]. Biol Blood Marrow Transplant, 2020, 26(6): 1195-1202. doi: 10.1016/j.bbmt.2020.02.009
[41] Vu CA, Rana MM, Jacobs SE, et al. Isavuconazole for the prophylaxis and treatment of invasive fungal disease: A single-center experience[J]. Transpl Infect Dis, 2021, 23(2): e13469.
[42] Bowen CD, Tallman GB, Hakki M, et al. Isavuconazole to prevent invasive fungal infection in immunocompromised adults: Initial experience at an academic medical centre[J]. Mycoses, 2019, 62(8): 665-672. doi: 10.1111/myc.12924
[43] Bogler Y, Stern A, Su Y, et al. Efficacy and safety of isavuconazole compared with voriconazole as primary antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients[J]. Med Mycol, 2021, 59(10): 970-979. doi: 10.1093/mmy/myab025
[44] Fontana L, Perlin DS, Zhao Y, et al. Isavuconazole prophylaxis in patients with hematologic malignancies and hematopoietic cell transplant recipients[J]. Clin Infect Dis, 2020, 70(5): 723-730. doi: 10.1093/cid/ciz282
[45] Bose P, McCue D, Wurster S, et al. Isavuconazole as Primary Antifungal Prophylaxis in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome: An Open-label, Prospective, Phase 2 Study[J]. Clin Infect Dis, 2021, 72(10): 1755-1763. doi: 10.1093/cid/ciaa358
[46] Feys S, Almyroudi MP, Braspenning R, et al. A Visual and Comprehensive Review on COVID-19-Associated Pulmonary Aspergillosis(CAPA)[J]. J Fungi(Basel), 2021, 7(12): 1067.
[47] Desai A, Schmitt-Hoffmann AH, Mujais S, et al. Population Pharmacokinetics of Isavuconazole in Subjects with Mild or Moderate Hepatic Impairment[J]. Antimicrob Agents Chemother, 2016, 60(5): 3025-3031. doi: 10.1128/AAC.02942-15
[48] Huang H, Xie H, Chaphekar N, et al. A physiologically based pharmacokinetic analysis to predict the pharmacokinetics of intravenous isavuconazole in patients with or without hepatic impairment[J]. Antimicrob Agents Chemother, 2021, 65(5): e02032-20.
[49] Zhou ZX, Yin XD, Zhang Y, et al. Antifungal Drugs and Drug-Induced Liver Injury: A Real-World Study Leveraging the FDA Adverse Event Reporting System Database[J]. Front Pharmacol, 2022, 13: 891336. doi: 10.3389/fphar.2022.891336
[50] DiPippo AJ, Rausch CR, Kontoyiannis DP. Tolerability of isavuconazole after posaconazole toxicity in leukaemia patients[J]. Mycoses, 2019, 62(1): 81-86. doi: 10.1111/myc.12851
[51] Biagi M, Butler D, Tan X, et al. Pharmacokinetics and Dialytic Clearance of Isavuconazole During In Vitro and In Vivo Continuous Renal Replacement Therapy[J]. Antimicrob Agents Chemother, 2019, 63(12): e01085-19.
[52] Zurl C, Waller M, Schwameis F, et al. Isavuconazole Treatment in a Mixed Patient Cohort with Invasive Fungal Infections: Outcome, Tolerability and Clinical Implications of Isavuconazole Plasma Concentrations[J]. J Fungi(Basel), 2020, 6(2): 90.
[53] Mullane KM, Aoun M, Franks B, et al. Safety and outcomes in Aspergillus patients with renal vs. non-renal impairment treated with isavuconazole: Experience from the SECURE(randomised)and the VITAL trials[J]. ECCMID, 2015, EV0932.
[54] A Study to Evaluate Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis(IA)or Invasive Mucormycosis(IM)in Pediatric Participants[EB/OL].
https://clinicaltrials.gov/ct2/show/NCT03816176?term=isavuconazole+pediatric&phase=0123&draw=2&rank=2 access at Mar. 25th2023.[55] Shi M, Chen L, Yang Y, et al. Analysis of clinical features and outcomes of 161 patients with severe and critical COVID-19: A multicenter descriptive study[J]. J Clin Lab Anal, 2020, 34(9): e23415.
[56] Ohshimo S, Liu K, Ogura T, et al. Trends in survival during the pandemic in patients with critical COVID-19 receiving mechanical ventilation with or without ECMO: analysis of the Japanese national registry data[J]. Crit Care, 2022, 26(1): 354. doi: 10.1186/s13054-022-04187-7
[57] Koehler P, Bassetti M, Chakrabarti A, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance[J]. Lancet Infect Dis, 2021, 21(6): e149-e162. doi: 10.1016/S1473-3099(20)30847-1
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