Utility of triazole antifungal therapeutic drug monitoring: Insights from the Society of Infectious Diseases Pharmacists

McCreary, Erin K; Davis, Matthew; Narayanan, Navaneeth; Andes, David R.; Cattaneo, Dario; Christian, Robbie; Lewis, Russell E.; Watt, Kevin M.; Wiederhold, Nathan P.; Johnson, Melissa D.

doi:10.1002/phar.2850

Cited by 26 publications

(8 citation statements)

References 44 publications

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“…Portugal is still very much behind concerning TDM, with only a few institutions with the capacity to conduct such analyses. This process holds significant importance as it provides insight into appropriate drug dosages and potential adverse effects, enabling treatment optimizations [ 56 ]. Besides flucytosine, only the prescription of certain triazoles is monitored in these institutions.…”

Section: Discussionmentioning

confidence: 99%

Multicentric Study on the Clinical Mycology Capacity and Access to Antifungal Treatment in Portugal

Fernandes,

Sabino,

Cunha

et al. 2024

Mycopathologia

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The success of the clinical management of invasive fungal diseases (IFD) is highly dependent on suitable tools for timely and accurate diagnosis for effective treatment. An in-depth analysis of the ability of European institutions to promptly and accurately diagnose IFD was previously conducted to identify limitations and aspects to improve. Here, we evaluated and discussed the specific case of Portugal, for which, to our knowledge, there are no reports describing the national mycological diagnostic capacity and access to antifungal treatment. Data from 16 Portuguese medical institutions were collected via an online electronic case report form covering different parameters, including institution profile, self-perceived IFD incidence, target patients, diagnostic methods and reagents, and available antifungals. The majority of participating institutions (69%) reported a low-very low incidence of IFD, with Candida spp. indicated as the most relevant fungal pathogen, followed by Aspergillus spp. and Cryptococcus spp. All institutions had access to culture and microscopy, whereas 94 and 88% were able to run antigen-detection assays and molecular tests, respectively. All of the institutions capable of providing antifungal therapy declared to have access to at least one antifungal. However, echinocandins were only available at 85% of the sites. Therapeutic drug monitoring (TDM) was reported to remain a very restricted practice in Portugal, being available in 19% of the institutions, with the TDM of itraconazole and posaconazole performed in only 6% of them. Importantly, several of these resources are outsourced to external entities. Except for TDM, Portugal appears to be well-prepared concerning the overall capacity to diagnose and treat IFD. Future efforts should focus on promoting the widespread availability of TDM and improved access to multiple classes of antifungals, to further improve patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Multicentric Study on the Clinical Mycology Capacity and Access to Antifungal Treatment in Portugal

Fernandes,

Sabino,

Cunha

et al. 2024

Mycopathologia

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“…Voriconazole has been shown to have a low barrier for resistance, while posaconazole remained active in strains with fluconazole resistance [99]. Furthermore, voriconazole has been associated with increased mortality in the first 42 days when compared to itraconazole [100]. Isavuconazole also displayed a higher barrier to resistance and may be effective as step-down oral therapy for histoplasmosis [101].…”

Section: Managementmentioning

confidence: 99%

“…Conversely, the oral solution is better absorbed on an empty stomach and is not affected by acid-suppressive therapies. Given the variable pharmacokinetic, therapeutic drug monitoring is recommended in all patients [100]. The metabolism of itraconazole produces an extensive number of metabolites; of those, hydroxyitraconazole has been found to have antifungal activity which is comparable to the parent drug [99].…”

Section: Managementmentioning

confidence: 99%

“…The therapeutic target level of itraconazole/hydroxyitraconazole for the treatment of histoplasmosis is unknown, and the current recommendations of maintaining levels of at least 1.0 mcg/mL are derived from extrapolation of other fungal infections [100][101][102]. In patients with oropharyngeal candidiasis, itraconazole serum concentrations <1.0 mcg/mL were associated with treatment failures [103].…”

Section: Managementmentioning

confidence: 99%

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Histoplasmosis in Solid Organ Transplantation

Barros,

Wheat

2024

JoF

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Histoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. It has a broad global distribution with shifting epidemiology during recent decades. While in immunocompetent individuals infection is usually self-resolving, solid organ transplant recipients are at increased risk of symptomatic disease with dissemination to extrapulmonary tissue. Diagnosis of histoplasmosis relies on direct observation of the pathogen (histopathology, cytopathology, and culture) or detection of antigens, antibodies, or nucleic acids. All transplant recipients with histoplasmosis warrant therapy, though the agent of choice and duration of therapy depends on the severity of disease. In the present article, we describe the pathogenesis, epidemiology, clinical manifestations and management of histoplasmosis in solid organ transplant recipients.

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“…It is the sum of both plasma concentrations that amounts to the total bioactive drug, and It is this that should be used to determine appropriate dosing. 140 The field of TDM continues to evolve, and whilst obvious challenges remain, namely difficulties with timely access to assays, adherence to quality assurance processes and turnaround time of results, as well as access to appropriate dose adjustment software and expertise, it remains a crucial aspect in the management of these patients.…”

Section: Drugmentioning

confidence: 99%

Approach to diagnostic evaluation and prevention of invasive fungal disease in patients prior to allogeneic hematopoietic stem cell transplant

O'Keeffe,

Singh,

Slavin

2023

Transplant Infectious Dis

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In recent years, advancements in the treatment landscape for hematological malignancies, such as acute myeloid leukemia and acute lymphoblastic leukemia, have significantly improved disease prognosis and overall survival. However, the treatment landscape is changing and the emergence of targeted oral therapies and immune‐based treatments has brought forth new challenges in evaluating and preventing invasive fungal diseases (IFDs). IFD disproportionately affects immunocompromised hosts, particularly those undergoing therapy for acute leukemia and allogeneic hematopoietic stem cell transplant. This review aims to provide a comprehensive overview of the pretransplant workup, identification, and prevention of IFD in patients with hematological malignancy. The pretransplant period offers a critical window to assess each patient's risk factors and implement appropriate prophylactic measures. Risk assessment includes evaluation of disease, host, prior treatments, and environmental factors, allowing a dynamic evaluation that considers disease progression and treatment course. Diagnostic screening, involving various biomarkers and radiological modalities, plays a crucial role in early detection of IFD. Antifungal prophylaxis choice is based on available evidence as well as individual risk assessment, potential for drug–drug interactions, toxicity, and patient adherence. Therapeutic drug monitoring ensures effective antifungal stewardship and optimal treatment. Patient education and counselling are vital in minimizing environmental exposures to fungal pathogens and promoting medication adherence. A well‐structured and individualized approach, encompassing risk assessment, prophylaxis, surveillance, and patient education, is essential for effectively preventing IFD in hematological malignancies, ultimately leading to improved patient outcomes and overall survival.

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Utility of triazole antifungal therapeutic drug monitoring: Insights from the Society of Infectious Diseases Pharmacists

Cited by 26 publications

References 44 publications

Multicentric Study on the Clinical Mycology Capacity and Access to Antifungal Treatment in Portugal

Multicentric Study on the Clinical Mycology Capacity and Access to Antifungal Treatment in Portugal

Histoplasmosis in Solid Organ Transplantation

Approach to diagnostic evaluation and prevention of invasive fungal disease in patients prior to allogeneic hematopoietic stem cell transplant

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