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

Teresa Peláez-García de la Rasilla,

Álvaro Mato-López,

Clara E. Pablos-Puertas

et al.

Journal of Fungi, Journal Year: 2023, Volume and Issue: 9(8), P. 805 - 805

Published: July 30, 2023

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

Language: Английский

Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease DOI
Martin Hoenigl, Amir Arastehfar, Maiken Cavling Arendrup

et al.

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(2)

Published: April 11, 2024

SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, their utility efficacy in antifungal treatment limited one or more of innate acquired resistance some fungi, poor penetration into "sequestered" sites, agent-specific side effect which require frequent patient reassessment monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, fungicidal mechanism(s) urgently needed. Here, we provide comprehensive review agents, both improved known mechanisms actions new currently clinical development for treating invasive yeast, mold (filamentous fungi),

Language: Английский

Citations

40
Drug tolerance and persistence in bacteria, fungi and cancer cells: Role of non-genetic heterogeneity DOI Creative Commons
Imane El Meouche, Paras Jain, Mohit Kumar Jolly

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 49, P. 102069 - 102069

Published: Aug. 8, 2024

Language: Английский

Citations

7
In Vitro Susceptibility Tests in the Context of Antifungal Resistance: Beyond Minimum Inhibitory Concentration in Candida spp. DOI Creative Commons
Iacopo Franconi, Antonella Lupetti

Journal of Fungi, Journal Year: 2023, Volume and Issue: 9(12), P. 1188 - 1188

Published: Dec. 12, 2023

Antimicrobial resistance is a matter of rising concern, especially in fungal diseases. Multiple reports all over the world are highlighting worrisome increase azole- and echinocandin-resistance among pathogens, Candida species, as reported recently published pathogens priority list made by WHO. Despite continuous efforts advances infection control, development new antifungal molecules, research on molecular mechanisms scientific community, trends invasive diseases associated rise, hindering therapeutic options clinical cures. In this context, vitro susceptibility testing aimed at evaluating minimum inhibitory concentrations, still milestone management However, such not only type microbiologist’s disposal. There other adjunctive tests fungicidal activity molecules also exploring tolerance to antifungals. This plethora left behind performed for purposes, but their role context with might add resourceful information patients. The aim review was therefore revise explore that could be potentially implemented current practice resistant difficult-to-treat cases.

Language: Английский

Citations

10
Toward the consensus of definitions for the phenomena of antifungal tolerance and persistence in filamentous fungi DOI Creative Commons
Jorge Amich, Michael Bromley, Gustavo H. Goldman

et al.

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

ABSTRACT Antifungal drug tolerance and persistence are being increasingly recognized in fungal pathogens. Accordingly, more research is carried out to characterize understand these phenomena. However, the terminology methodology employed community lack consensus, particularly for filamentous fungi, as they present further complexities when compared single-celled microorganisms. Hence, with aim ensure consistency literature, this Perspective article, we propose tailored definitions fungi suggest methods detect investigate phenomena laboratory.

Language: Английский

Citations

0
Aspergillus fumigatus mitogenomes and their influence on azole-resistant and -susceptible populations DOI Creative Commons
Endrews Delbaje, Laís Pontes, Johanna Rhodes

et al.

npj Antimicrobials and Resistance, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 27, 2025

Abstract The role of the fungal mitochondria goes far beyond energy metabolism. genomes 318 Aspergillus fumigatus clinical and environmental isolates from different geographic origins were analyzed aiming to study mitochondrial sequences populations sensitive resistant azoles. Our results show that A. mitogenomic are very conserved only variation in small intergenic regions one intronic sequence cox 3 gene. Furthermore, a genome-wide association analysis accessory genes revealed potential mitochondria-based genotypes may interact synergistically with ergosterol biosynthesis pathway confer phenotype. This includes mutation AMID-like oxidoreductase ( aifA , AFUA_3G01290) absence carrier protein pet8 AFUA_8G01400). Deletion these did not change azole-susceptibility but increased azole-persistence, suggesting could be involved azole-persistence. work opens new hypotheses for involvement azole-resistance.

Language: Английский

Citations

0
Rapid Therapeutic Drug Monitoring of Voriconazole Based on High-Performance Liquid Chromatography: A Single-Center Pilot Study in Outpatients DOI Creative Commons
Satoru Morikawa, Y Yagi,

Moemi Okazaki

et al.

Antibiotics, Journal Year: 2025, Volume and Issue: 14(5), P. 474 - 474

Published: May 8, 2025

Background/Objectives: Voriconazole (VRCZ) use requires accurate monitoring to avoid suboptimal drug levels and adverse effects. In addition, the appearance of resistant fungal strains is a problem that needs attention. Blood concentration measurement technique choice; however, it slow, limiting its clinical application. This study aimed evaluate utility rapid therapeutic (TDM) for VRCZ using high-performance liquid chromatography with ultraviolet detection (HPLC-UV) compared conventional outsourced chromatography–tandem mass spectrometry (LC-MS/MS) testing in outpatient care. Methods: blood concentrations were measured HPLC-UV LC-MS/MS. Reporting times, accuracy, outcomes assessed outpatients receiving treatment. Safety was monitored renal, hepatic, visual toxicities. Results: significantly reduced reporting times (0.433 h vs. 74.3 h, p < 0.001), Deming’s regression analyses showed strong correlation LC-MS/MS results (Pearson’s r = 0.988). Bland–Altman analysis an average difference 0.025 μg/mL between Prospective three revealed no events, enabling safe effective dosing. Conclusions: Rapid TDM cost-effective feasible approach care, improving patient safety. Further studies cross-facility collaboration are needed expand

Language: Английский

Citations

0
Adaptation Under Pressure: Resistance and Stress Response Interplay in Clinical Aspergillus fumigatus Isolates DOI Creative Commons

Ivana Segéňová,

Ján Víglaš,

Tomáš Pagáč

et al.

Journal of Fungi, Journal Year: 2025, Volume and Issue: 11(6), P. 428 - 428

Published: June 2, 2025

Understanding the interplay between antifungal resistance, stress adaptation, and virulence in Aspergillus fumigatus is critical for more effective treatment outcomes. In this study, we investigate six clinical isolates of A. from hospitals Czech Republic, focusing on their resistance profiles, responses, survival mechanisms under pressure. Notably, have shown that azole-susceptible strains were able to form persister cells supra-MIC concentrations, highlighting an emerging non-genetic mechanism. Stress response profiling demonstrated differential susceptibility agents targeting signal transduction pathways, as principal component analysis proved even azole-resistant might rely these pathways. Combinatorial with posaconazole dithiothreitol enhanced efficacy regardless strains. Fitness assays revealed azole imposed a competitive disadvantage azole-free conditions. vivo assessment Galleria mellonella larvae strain-specific pathogenicity did not directly correlate resistance. Together, our findings illustrate multifactorial nature fungal emphasize tolerance, persistence significantly affect outcomes, absence classical mechanisms. Targeting pathways emerges promising strategy enhance existing manage fumigatus.

Language: Английский

Citations

0
Treatment alternatives for multidrug-resistant fungal pathogens DOI
Kevin Roe

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(6), P. 103596 - 103596

Published: April 20, 2023

Language: Английский

Citations

4
First Report of Azole-Resistant Aspergillus fumigatus with TR46/Y121F/T289A Mutations in Kuwait and an Update on Their Occurrence in the Middle East DOI Creative Commons
Mohammad Asadzadeh, Khaled Alobaid, Suhail Ahmad

et al.

Journal of Fungi, Journal Year: 2023, Volume and Issue: 9(8), P. 784 - 784

Published: July 25, 2023

Pulmonary aspergillosis is a common fungal infection with several clinical manifestations including invasive, allergic and chronic chest diseases. Invasive pulmonary (IPA) leading cause of death in immunocompromised patients, particularly those receiving chemotherapy among bone marrow transplant recipients. Aspergillus fumigatus the most prevalent causative agent voriconazole first-line therapy for IPA. In this study, we report first isolation voriconazole-resistant A. carrying TR46/Y121F/T289A mutations from an pregnant lady Kuwait. The patient was successfully treated probable respiratory caspofungin voriconazole. literature review PubMed has identified itraconazole-resistant environmental isolates TR34/L98H cyp51A Middle Eastern countries However, have not been reported previously any country region while only Iran. source CYP51A mutant our remained unknown. Surveillance azole resistance warranted

Language: Английский

Citations

2
Reversing olorofim activity reveals multifactorial drug tolerance inAspergillus fumigatus DOI Creative Commons
Clara Valero,

M. Annunciata McManus,

Ashva Ram Anna Durai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 21, 2023

Withdrawal Statement The authors have withdrawn their manuscript owing to finding new evidence contradictory the results and conclusions presented in this work. Therefore, do not wish work be cited as reference for project. If you any questions, please contact corresponding author.

Language: Английский

Citations

1