Cargando…

Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease

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 chara...

Descripción completa

Detalles Bibliográficos
Autores principales: Nwankwo, Lisa, Gilmartin, Desmond, Matharu, Sheila, Nuh, Ali, Donovan, Jackie, Armstrong-James, Darius, Shah, Anand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029347/
https://www.ncbi.nlm.nih.gov/pubmed/35448593
http://dx.doi.org/10.3390/jof8040362
_version_ 1784691855350300672
author Nwankwo, Lisa
Gilmartin, Desmond
Matharu, Sheila
Nuh, Ali
Donovan, Jackie
Armstrong-James, Darius
Shah, Anand
author_facet Nwankwo, Lisa
Gilmartin, Desmond
Matharu, Sheila
Nuh, Ali
Donovan, Jackie
Armstrong-James, Darius
Shah, Anand
author_sort Nwankwo, Lisa
collection PubMed
description 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 (r(pb) = 0.31; p = 0.021) and male sex (φ(c) = 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.
format Online
Article
Text
id pubmed-9029347
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90293472022-04-23 Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease Nwankwo, Lisa Gilmartin, Desmond Matharu, Sheila Nuh, Ali Donovan, Jackie Armstrong-James, Darius Shah, Anand J Fungi (Basel) Article 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 (r(pb) = 0.31; p = 0.021) and male sex (φ(c) = 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. MDPI 2022-03-31 /pmc/articles/PMC9029347/ /pubmed/35448593 http://dx.doi.org/10.3390/jof8040362 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nwankwo, Lisa
Gilmartin, Desmond
Matharu, Sheila
Nuh, Ali
Donovan, Jackie
Armstrong-James, Darius
Shah, Anand
Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease
title Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease
title_full Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease
title_fullStr Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease
title_full_unstemmed Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease
title_short Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease
title_sort experience of isavuconazole as a salvage therapy in chronic pulmonary fungal disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029347/
https://www.ncbi.nlm.nih.gov/pubmed/35448593
http://dx.doi.org/10.3390/jof8040362
work_keys_str_mv AT nwankwolisa experienceofisavuconazoleasasalvagetherapyinchronicpulmonaryfungaldisease
AT gilmartindesmond experienceofisavuconazoleasasalvagetherapyinchronicpulmonaryfungaldisease
AT matharusheila experienceofisavuconazoleasasalvagetherapyinchronicpulmonaryfungaldisease
AT nuhali experienceofisavuconazoleasasalvagetherapyinchronicpulmonaryfungaldisease
AT donovanjackie experienceofisavuconazoleasasalvagetherapyinchronicpulmonaryfungaldisease
AT armstrongjamesdarius experienceofisavuconazoleasasalvagetherapyinchronicpulmonaryfungaldisease
AT shahanand experienceofisavuconazoleasasalvagetherapyinchronicpulmonaryfungaldisease