Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease
<b>Background:</b> 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 isavuconaz...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Journal of Fungi |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2309-608X/8/4/362 |
| _version_ | 1797410569910747136 |
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| author | Lisa Nwankwo Desmond Gilmartin Sheila Matharu Ali Nuh Jackie Donovan Darius Armstrong-James Anand Shah |
| author_facet | Lisa Nwankwo Desmond Gilmartin Sheila Matharu Ali Nuh Jackie Donovan Darius Armstrong-James Anand Shah |
| author_sort | Lisa Nwankwo |
| collection | DOAJ |
| description | <b>Background:</b> 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. <b>Aims:</b> To characterise the prevalence of isavuconazole resistance and use in a tertiary respiratory centre. <b>Methods:</b> A retrospective observational analysis (2016–2021) of adult respiratory patients analysing fungal culture, therapeutic drug monitoring, and outcome post-isavuconazole therapy. <b>Results</b>: During the study period, isavuconazole susceptibility testing was performed on 26 <i>Aspergillus</i> spp. isolates. A total of 80.8% of <i>A. fumigatus</i> isolates had isavuconazole (MIC > 1 mg/L, and 73.0% > 2 mg/L) with a good correlation to voriconazole MIC (r = 0.7, <i>p</i> = 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 <i>(r<sub>pb</sub></i> = 0.31; <i>p</i> = 0.021) and male sex (φ<sub>c</sub> = 0.30; <i>p</i> = 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. <b>Conclusion</b>: 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. |
| first_indexed | 2024-03-09T04:32:06Z |
| format | Article |
| id | doaj.art-8f06d75b87e3464d81ed7ca59bc46581 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T04:32:06Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-8f06d75b87e3464d81ed7ca59bc465812023-12-03T13:34:35ZengMDPI AGJournal of Fungi2309-608X2022-03-018436210.3390/jof8040362Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal DiseaseLisa Nwankwo0Desmond Gilmartin1Sheila Matharu2Ali Nuh3Jackie Donovan4Darius Armstrong-James5Anand Shah6Pharmacy Department, Royal Brompton Hospital, Guy’s and St. Thomas’ NHS Foundation Trust, London SW3 6NP, UKClinical Informatics, Royal Brompton and Harefield Hospital Foundation NHS Trust, Fulham, London SW3 6HP, UKClinical Informatics, Royal Brompton and Harefield Hospital Foundation NHS Trust, Fulham, London SW3 6HP, UKMicrobiology Department, Royal Brompton Hospital, Guy’s and St. Thomas’ NHS Foundation Trust, London SW3 6NP, UKDepartment of Pathology, Royal Brompton and Harefield NHS Foundation Trust, London SW3 6NP, UKMicrobiology Department, Royal Brompton Hospital, Guy’s and St. Thomas’ NHS Foundation Trust, London SW3 6NP, UKDepartment of Respiratory Medicine, Royal Brompton Hospital, Guy’s and St. Thomas’ NHS Foundation Trust, London SW3 6NP, UK<b>Background:</b> 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. <b>Aims:</b> To characterise the prevalence of isavuconazole resistance and use in a tertiary respiratory centre. <b>Methods:</b> A retrospective observational analysis (2016–2021) of adult respiratory patients analysing fungal culture, therapeutic drug monitoring, and outcome post-isavuconazole therapy. <b>Results</b>: During the study period, isavuconazole susceptibility testing was performed on 26 <i>Aspergillus</i> spp. isolates. A total of 80.8% of <i>A. fumigatus</i> isolates had isavuconazole (MIC > 1 mg/L, and 73.0% > 2 mg/L) with a good correlation to voriconazole MIC (r = 0.7, <i>p</i> = 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 <i>(r<sub>pb</sub></i> = 0.31; <i>p</i> = 0.021) and male sex (φ<sub>c</sub> = 0.30; <i>p</i> = 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. <b>Conclusion</b>: 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.https://www.mdpi.com/2309-608X/8/4/362antifungal resistanceisavuconazolecystic fibrosispulmonary diseaseaspergillus fumigatuspulmonary aspergillosis |
| spellingShingle | Lisa Nwankwo Desmond Gilmartin Sheila Matharu Ali Nuh Jackie Donovan Darius Armstrong-James Anand Shah Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease Journal of Fungi antifungal resistance isavuconazole cystic fibrosis pulmonary disease aspergillus fumigatus pulmonary aspergillosis |
| 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 | antifungal resistance isavuconazole cystic fibrosis pulmonary disease aspergillus fumigatus pulmonary aspergillosis |
| url | https://www.mdpi.com/2309-608X/8/4/362 |
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