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.
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
01 03 2023
01 03 2023
Historique:
pubmed:
12
11
2022
medline:
25
2
2023
entrez:
11
11
2022
Statut:
ppublish
Résumé
Isavuconazole has theoretical advantages over other mold-active triazoles for the treatment of invasive aspergillosis and mucormycosis after solid organ transplantation (SOT). The available clinical experience, nevertheless, is scarce. We performed a retrospective study including all adult SOT recipients with proven or probable invasive mold disease (IMD) that received isavuconazole for ≥24 h as first-line or salvage therapy at 10 Spanish centers between September 2017 and November 2021. The primary efficacy outcome was clinical response (complete or partial resolution of attributable symptoms and findings) by weeks 6 and 12. Safety outcomes included the rates of treatment-emergent adverse events and premature isavuconazole discontinuation. We included 81 SOT recipients that received isavuconazole for a median of 58.0 days because of invasive aspergillosis (n = 71) or mucormycosis (n = 10). Isavuconazole was used as first-line (72.8%) or salvage therapy due because of previous treatment-emergent toxicity (11.1%) or refractory IMD (7.4%). Combination therapy was common (37.0%), mainly with an echinocandin or liposomal amphotericin B. Clinical response by weeks 6 and 12 was achieved in 53.1% and 54.3% of patients, respectively, and was more likely when isavuconazole was administered as first-line single-agent therapy. At least 1 treatment-emergent adverse event occurred in 17.3% of patients, and 6.2% required premature discontinuation. Daily tacrolimus dose was reduced in two-thirds of patients by a median of 50.0%, although tacrolimus levels remained stable throughout the first month of therapy. Isavuconazole is a safe therapeutic option for IMD in SOT recipients, with efficacy comparable to other patient groups.
Sections du résumé
BACKGROUND
Isavuconazole has theoretical advantages over other mold-active triazoles for the treatment of invasive aspergillosis and mucormycosis after solid organ transplantation (SOT). The available clinical experience, nevertheless, is scarce.
METHODS
We performed a retrospective study including all adult SOT recipients with proven or probable invasive mold disease (IMD) that received isavuconazole for ≥24 h as first-line or salvage therapy at 10 Spanish centers between September 2017 and November 2021. The primary efficacy outcome was clinical response (complete or partial resolution of attributable symptoms and findings) by weeks 6 and 12. Safety outcomes included the rates of treatment-emergent adverse events and premature isavuconazole discontinuation.
RESULTS
We included 81 SOT recipients that received isavuconazole for a median of 58.0 days because of invasive aspergillosis (n = 71) or mucormycosis (n = 10). Isavuconazole was used as first-line (72.8%) or salvage therapy due because of previous treatment-emergent toxicity (11.1%) or refractory IMD (7.4%). Combination therapy was common (37.0%), mainly with an echinocandin or liposomal amphotericin B. Clinical response by weeks 6 and 12 was achieved in 53.1% and 54.3% of patients, respectively, and was more likely when isavuconazole was administered as first-line single-agent therapy. At least 1 treatment-emergent adverse event occurred in 17.3% of patients, and 6.2% required premature discontinuation. Daily tacrolimus dose was reduced in two-thirds of patients by a median of 50.0%, although tacrolimus levels remained stable throughout the first month of therapy.
CONCLUSIONS
Isavuconazole is a safe therapeutic option for IMD in SOT recipients, with efficacy comparable to other patient groups.
Identifiants
pubmed: 36367924
doi: 10.1097/TP.0000000000004312
pii: 00007890-202303000-00032
doi:
Substances chimiques
isavuconazole
60UTO373KE
Antifungal Agents
0
Tacrolimus
WM0HAQ4WNM
Triazoles
0
Nitriles
0
Types de publication
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
762-773Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
Gavaldà J, Meije Y, Fortún J, et al.; ESCMID Study Group for Infections in Compromised Hosts. Invasive fungal infections in solid organ transplant recipients. Clin Microbiol Infect. 2014;20(Suppl 7):27–48.
Pappas PG, Alexander BD, Andes DR, et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis. 2010;50:1101–1111.
Gioia F, Filigheddu E, Corbella L, et al. Invasive aspergillosis in solid organ transplantation: diagnostic challenges and differences in outcome in a Spanish national cohort (Diaspersot study). Mycoses. 2021;64:1334–1345.
López-Medrano F, Fernández-Ruiz M, Silva JT, et al.; Spanish Network for Research in Infectious Diseases (REIPI), the Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC), the Study Group for Infections in Compromised Hosts (ESGICH) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and the Swiss Transplant Cohort Study (STCS). Clinical presentation and determinants of mortality of invasive pulmonary aspergillosis in kidney transplant recipients: a multinational cohort study. Am J Transplant. 2016;16:3220–3234.
Husain S, Camargo JF. Invasive aspergillosis in solid-organ transplant recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of practice. Clin Transplant. 2019;33:e13544.
Gavalda J, Len O, San Juan R, et al.; RESITRA (Spanish Network for Research on Infection in Transplantation). Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study. Clin Infect Dis. 2005;41:52–59.
Barchiesi F, Mazzocato S, Mazzanti S, et al. Invasive aspergillosis in liver transplant recipients: epidemiology, clinical characteristics, treatment, and outcomes in 116 cases. Liver Transpl. 2015;21:204–212.
Herbrecht R, Denning DW, Patterson TF, et al.; Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–415.
Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24(Suppl 1):e1–e38.
Garcia-Vidal C, Alastruey-Izquierdo A, Aguilar-Guisado M, et al. Executive summary of clinical practice guideline for the management of invasive diseases caused by Aspergillus : 2018 update by the GEMICOMED-SEIMC/REIPI. Enferm Infecc Microbiol Clin (Engl Ed). 2019;37:535–541.
Patterson TF, Thompson GR III, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63:e1–e60.
Li X, Yu C, Wang T, et al. Effect of cytochrome P450 2C19 polymorphisms on the clinical outcomes of voriconazole: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2016;72:1185–1193.
Wang T, Zhu H, Sun J, et al. Efficacy and safety of voriconazole and CYP2C19 polymorphism for optimised dosage regimens in patients with invasive fungal infections. Int J Antimicrob Agents. 2014;44:436–442.
Johnson HJ, Han K, Capitano B, et al. Voriconazole pharmacokinetics in liver transplant recipients. Antimicrob Agents Chemother. 2010;54:852–859.
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. Transpl Infect Dis. 2017;19. doi: 10.1111/tid.12751.
doi: 10.1111/tid.12751
Turner RB, Martello JL, Malhotra A. Worsening renal function in patients with baseline renal impairment treated with intravenous voriconazole: a systematic review. Int J Antimicrob Agents. 2015;46:362–366.
Hamandi B, Fegbeutel C, Silveira FP, et al. Voriconazole and squamous cell carcinoma after lung transplantation: a multicenter study. Am J Transplant. 2018;18:113–124.
Elmore S, Wisse A, Chapin RW, et al. Voriconazole-associated periostitis presenting as hypertrophic osteoarthropathy following lung transplantation report of two cases and review of the literature. Semin Arthritis Rheum. 2019;49:319–323.
Petraitis V, Petraitiene R, Moradi PW, et al. Pharmacokinetics and concentration-dependent efficacy of isavuconazole for treatment of experimental invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2016;60:2718–2726.
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. Antimicrob Agents Chemother. 2017;61:e01292–e01217.
Ordaya EE, Alangaden GJ. Real-life use of isavuconazole in patients intolerant to other azoles. Clin Infect Dis. 2016;63:1529–1530.
Dalla Gasperina D, Lombardi D, Rovelli C, et al. Successful treatment with isavuconazole of subcutaneous phaeohyphomycosis in a kidney transplant recipient. Transpl Infect Dis. 2019;21:e13197.
Rivosecchi RM, Clancy CJ, Shields RK, et al. Effects of isavuconazole on the plasma concentrations of tacrolimus among solid-organ transplant patients. Antimicrob Agents Chemother. 2017;61:e00970–e00917.
Wu X, Venkataramanan R, Rivosecchi RM, et al. Population pharmacokinetics of intravenous isavuconazole in solid-organ transplant recipients. Antimicrob Agents Chemother. 2020;64:e01728–e01719.
Monforte A, Los-Arcos I, Martín-Gómez MT, et al. Safety and effectiveness of isavuconazole treatment for fungal infections in solid organ transplant recipients (ISASOT Study). Microbiol Spectr. 2022;10:e0178421.
Aguado JM, Herrero JA, Gavaldá J, et al. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA. Transplantation. 1997;63:1278–1286.
López-Medrano F, Silva JT, Fernández-Ruiz M, et al.; Spanish Network for Research in Infectious Diseases (REIPI), the Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC), the Study Group for Infections in Compromised Hosts (ESGICH) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and the Swiss Transplant Cohort Study (STCS). Risk factors associated with early invasive pulmonary aspergillosis in kidney transplant recipients: results from a multinational matched case-control study. Am J Transplant. 2016;16:2148–2157.
Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2020;71:1367–1376.
Koehler P, Bassetti M, Chakrabarti A, et al.; European Confederation of Medical Mycology; International Society for Human Animal Mycology; Asia Fungal Working Group; INFOCUS LATAM/ISHAM Working Group; ISHAM Pan Africa Mycology Working Group; European Society for Clinical Microbiology; Infectious Diseases Fungal Infection Study Group; ESCMID Study Group for Infections in Critically Ill Patients; Interregional Association of Clinical Microbiology and Antimicrobial Chemotherapy; Medical Mycology Society of Nigeria; Medical Mycology Society of China Medicine Education Association; Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology; Association of Medical Microbiology; Infectious Disease Canada. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. 2021;21:e149–e162.
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. Lancet. 2016;387:760–769.
Cornely OA, Hoenigl M, Lass-Flörl C, et al.; Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM). Defining breakthrough invasive fungal infection-Position paper of the Mycoses Study Group Education and Research Consortium and the European Confederation of Medical Mycology. Mycoses. 2019;62:716–729.
Marty FM, Ostrosky-Zeichner L, Cornely OA, et al.; VITAL and FungiScope Mucormycosis Investigators. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16:828–837.
Neofytos D, Chatzis O, Nasioudis D, et al.; Swiss Transplant Cohort Study. Epidemiology, risk factors and outcomes of invasive aspergillosis in solid organ transplant recipients in the Swiss Transplant Cohort Study. Transpl Infect Dis. 2018;20:e12898.
Dagher H, Hachem R, Chaftari AM, 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 Fungi (Basel). 2022;8:74.
Buil JB, Brüggemann RJM, Bedin Denardi L, et al. In vitro interaction of isavuconazole and anidulafungin against azole-susceptible and azole-resistant Aspergillus fumigatus isolates. J Antimicrob Chemother. 2020;75:2582–2586.
Gebremariam T, Gu Y, Singh S, et al. Combination treatment of liposomal amphotericin B and isavuconazole is synergistic in treating experimental mucormycosis. J Antimicrob Chemother. 2021;76:2636–2639.
Odysseos G, Mayr U, Bozsaki G, et al. Isavuconazole and liposomal Amphotericin B as successful combination therapy of refractory invasive candidiasis in a liver transplant recipient: a case report and literature review. Mycopathologia. 2022;187:113–120.
Kronig I, Masouridi-Levrat S, Chalandon Y, et al. Clinical considerations of isavuconazole administration in high-risk hematological patients: a single-center 5-year experience. Mycopathologia. 2021;186:775–788.
Thompson GR III, Garcia-Diaz J, Miceli MH, et al. Systemic antifungal therapy with isavuconazonium sulfate or other agents in adults with invasive mucormycosis or invasive aspergillosis (non-fumigatus): a multicentre, non-interventional registry study. Mycoses. 2022;65:186–198.
DiPippo AJ, Kontoyiannis DP. Lack of toxicity with long-term isavuconazole use in patients with hematologic malignancy. Clin Infect Dis. 2019;69:1624–1627.
Townsend R, Dietz A, Hale C, et al. Pharmacokinetic evaluation of CYP3A4-mediated drug-drug interactions of isavuconazole with rifampin, ketoconazole, midazolam, and ethinyl estradiol/norethindrone in healthy adults. Clin Pharmacol Drug Dev. 2017;6:44–53.
Wu X, Clancy CJ, Rivosecchi RM, et al. Pharmacokinetics of intravenous isavuconazole in solid-organ transplant recipients. Antimicrob Agents Chemother. 2018;62:e01643–e01618.