Use of triazoles for the treatment of invasive aspergillosis: A three‐year cohort analysis

Cheng, Matthew P.; Orejas, J.; Arbona‐Haddad, Esther; Bold, Tyler D.; Solomon, Isaac H.; Chen, Kaiwen; Pandit, Alisha; Kusztos, Amanda E.; Cummins, Kaelyn C.; Liakos, Alexis; Marty, Francisco M.; Koo, Sophia; Hammond, Sarah P.

doi:10.1111/myc.13013

Cited by 11 publications

(11 citation statements)

References 27 publications

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“…Furthermore, due to its spectrum of activity against many non‐ Aspergillus moulds, isavuconazole is an attractive option in the setting of severe and prolonged immunosuppression where coinfection by more than one fungus may be of concern 179 . However, while real‐world data support the safety and tolerability profile of isavuconazole in haematological patients for the treatment of IFD, 180 reports of IFD breakthrough and failure are increasing in the setting of prophylaxis and treatment 181–184 …”

Section: Question 9: What Recommendations Should Guide the First‐line Antifungal Treatment Of Ia In Haematology/oncology Patients?mentioning

confidence: 99%

“…179 However, while real-world data support the safety and tolerability profile of isavuconazole in haematological patients for the treatment of IFD, 180 reports of IFD breakthrough and failure are increasing in the setting of prophylaxis and treatment. [181][182][183][184] While both posaconazole oral suspension and delayedrelease tablets have demonstrated efficacy for prophylaxis of IA in haematology patients, and posaconazole is licensed for salvage treatment of invasive mould disease, there are limited published data to support its first-line use to treat IA. [185][186][187] However, a recently published multicentre, randomised controlled trial of posaconazole compared with voriconazole for first-line therapy of IA demonstrated non-inferiority of posaconazole to voriconazole for the outcomes of mortality and global clinical response, with improved tolerance to posaconazole compared to voriconazole.…”

Section: Azole-resistant a Fumigatus In Australiamentioning

confidence: 99%

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Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021

Douglas

Smibert

Bajel

et al. 2021

Internal Medicine Journal

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Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID‐19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological‐based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non‐culture methods employing fungal biomarkers in pre‐emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first‐line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological‐based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations.

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Section: Question 9: What Recommendations Should Guide the First‐line Antifungal Treatment Of Ia In Haematology/oncology Patients?mentioning

confidence: 99%

Section: Azole-resistant a Fumigatus In Australiamentioning

confidence: 99%

Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021

Douglas

Smibert

Bajel

et al. 2021

Internal Medicine Journal

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“…145 High procalcitonin levels are associated with a risk of supratherapeutic levels after the loading dose, 342 and serum albumin levels affect VRZ levels. 110,171 Despite its efficacy, 343 frequent safety issues have been reported for VRZ. Cases reports and studies suggest that high levels are associated with toxicity.…”

Section: Vrz Trendsmentioning

confidence: 99%

“…Despite its efficacy, 343 frequent safety issues have been reported for VRZ. Cases reports and studies suggest that high levels are associated with toxicity.…”

Section: Tdm For Af Drugsmentioning

confidence: 99%

Antifungal Drugs TDM: Trends and Update

Kably

Launay

Derobertmasure

et al. 2022

Therapeutic Drug Monitoring

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The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. Methods:We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-druginteraction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.Results: More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.Conclusions: TDM seems to be crucial for curative and/or longterm maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

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“…Twenty-seven consecutive adult patients had clinical sequencing in an evaluation of myeloid malignancy and were diagnosed with proven or probable IA from March 2015 through December 2017 (Figure 1A). 13…”

Section: Ia Cohortmentioning

confidence: 99%

Somatic GATA2 mutations define a subgroup of myeloid malignancy patients at high risk for invasive fungal disease

et al. 2020

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Invasive fungal disease (IFD) can be a severe treatment complication in patients with myeloid malignancies, but current risk models do not incorporate disease-specific factors, such as somatic gene mutations. Germline GATA2 deficiency is associated with a susceptibility to IFD. To determine whether myeloid gene mutations were associated with IFD risk, we identified 2 complementary cohorts of patients with myeloid malignancy, based on (1) the diagnosis of invasive aspergillosis (IA), or (2) the presence of GATA2 mutations identified during standard clinical sequencing. We found somatic GATA2 mutations in 5 of 27 consecutive patients who had myeloid malignancy and developed IA. Among 51 consecutive patients with GATA2 mutations identified in the evaluation of myeloid malignancy, we found that IFD was diagnosed and treated in 21 (41%), all of whom had received chemotherapy or had undergone an allogeneic stem cell transplant. Pulmonary infections and disseminated candidiasis were most common. The 90-day mortality was 52% among patients with IFD. Our results indicate that patients with somatic GATA2 mutations are a vulnerable subgroup of patients with myeloid malignancy who have high risk for treatment-associated IFD and suggest that a focused approach to antifungal prophylaxis be considered.

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Use of triazoles for the treatment of invasive aspergillosis: A three‐year cohort analysis

Abstract: Summary In a 3‐year cohort study of adult patients with proven or probable IA, fewer patients initially treated with isavuconazole experienced adverse events compared with voriconazole, but more patients required a change in therapy due to lack of clinical efficacy.

Cited by 11 publications

References 27 publications

Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021

Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021

Antifungal Drugs TDM: Trends and Update

Somatic GATA2 mutations define a subgroup of myeloid malignancy patients at high risk for invasive fungal disease

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