Invasive Aspergillosis and the Impact of Azole-resistance

Bosetti, Davide; Neofytos, Dionysios

doi:10.1007/s12281-023-00459-z

Cited by 12 publications

(14 citation statements)

References 141 publications

(205 reference statements)

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“…Undoubtedly, one major factor that has accounted for treatment failure in these cases is the severe immunosuppressed status of the patients. Invasive aspergillosis after allogeneic transplantation of hematopoietic progenitors, further complicated by GVHD, has associated mortality rates of around 50–100% [ 15 , 41 ]. Remarkably, when the infection is caused by resistant isolates, the mortality noticeably increases [ 41 ], demonstrating that an efficient antifungal treatment is still valuable and can provide a measurable benefit in these patient groups.…”

Section: Discussionmentioning

confidence: 99%

Potential Implication of Azole Persistence in the Treatment Failure of Two Haematological Patients Infected with Aspergillus fumigatus

Peláez-García de la Rasilla,

Mato-López,

Pablos-Puertas

et al. 2023

JoF

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Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients receiving allogeneic haematopoieticcell transplantation. The deep immunosuppression and a variety of potential additional complications developed in these patients result in IA reaching mortality rates of around 50–60%. This mortality is even higher when the patients are infected with azole-resistant isolates, demonstrating that, despite the complexity of management, adequate azole treatment can have a beneficial effect. It is therefore paramount to understand the reasons why antifungal treatment of IA infections caused by azole-susceptible isolates is often unsuccessful. In this respect, there are already various factors known to be important for treatment efficacy, for instance the drug concentrations achieved in the blood, which are thus often monitored. We hypothesize that antifungal persistence may be another important factor to consider. In this study we present two case reports of haematological patients who developed proven IA and suffered treatment failure, despite having been infected with susceptible isolates, receiving correct antifungal treatment and reaching therapeutic levels of the azole. Microbiological analysis of the recovered infective isolates showed that the patients were infected with multiple strains, several of which were persisters to voriconazole and/or isavuconazole. Therefore, we propose that azole persistence may have contributed to therapeutic failure in these patients and that this phenomenon should be considered in future studies.

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Section: Discussionmentioning

confidence: 99%

Potential Implication of Azole Persistence in the Treatment Failure of Two Haematological Patients Infected with Aspergillus fumigatus

Peláez-García de la Rasilla,

Mato-López,

Pablos-Puertas

et al. 2023

JoF

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“…The extensive and prolonged use of broad-spectrum azoles has significantly contributed to the widespread emergence of azole-resistant Aspergillus spp. These resistant strains have been linked to therapeutic failure and high mortality rates [ 62 , 63 ]. A single-center study reported that the prevalence of azole-resistant A. fumigatus among lung transplant patients was 17% [ 61 ].…”

Section: Culture Independent Diagnostic Assays For Invasive Aspergill...mentioning

confidence: 99%

Culture-independent diagnostic approaches for invasive aspergillosis in solid organ transplant recipients

Yoo,

Park

2023

Korean J Transplant

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Prompt and accurate diagnosis of invasive aspergillosis (IA) is crucial for immunocompromised patients, including those who have received a solid organ transplant (SOT). Despite their low sensitivity, microscopic detection and conventional culture are considered the 'gold standard' methods. In conjunction with conventional culture, culture-independent assays such as serum galactomannan testing and Aspergillus polymerase chain reaction (PCR) have been incorporated into the diagnostic process for IA. The recently revised consensus definitions from the European Organization for Research and Treatment of Cancer and the Mycosis Study Group have adjusted the threshold for positive galactomannan testing based on the sample type, and have excluded 1,3-β-D-glucan testing as a mycological criterion. Following extensive standardization efforts, positive Aspergillus PCR tests using serum, plasma, or bronchoalveolar lavage fluid have been added. However, there are limited studies evaluating the clinical utility of these culture-independent assays for the early diagnosis of IA in SOT recipients. Therefore, further research is required to determine whether these assays could aid in the early diagnosis of IA in SOT recipients, particularly in relation to the organ transplanted. In this review, we examine the culture-independent diagnostic methods for IA in SOT recipients, as well as the clinical utility of these assays.

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“…diverse challenges it poses in contemporary management. Of particular concern is the emergence of azole-resistant Aspergillus fumigatus strains [1]. Several countries, especially the Netherlands and Denmark, have reported increasing rates of Aspergillus fumigatus strains.…”

Section: Introductionmentioning

confidence: 99%

Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona, Spain

Monzo-Gallo,

Alastruey-Izquierdo,

Chumbita

et al. 2024

Infection

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Objectives We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months. Methods Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. Results Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. Conclusion We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.

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Invasive Aspergillosis and the Impact of Azole-resistance

Cited by 12 publications

References 141 publications

Potential Implication of Azole Persistence in the Treatment Failure of Two Haematological Patients Infected with Aspergillus fumigatus

Potential Implication of Azole Persistence in the Treatment Failure of Two Haematological Patients Infected with Aspergillus fumigatus

Culture-independent diagnostic approaches for invasive aspergillosis in solid organ transplant recipients

Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona, Spain

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