Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease

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

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What are the 100 most cited fungal genera?

Studies in Mycology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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Antifungal Resistance and the Role of New Therapeutic Agents

Current Infectious Disease Reports, Journal Year: 2022, Volume and Issue: 24(9), P. 105 - 116

Published: July 5, 2022

Language: Английский

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Pharmacodynamics, Mechanisms of Action and Resistance, and Spectrum of Activity of New Antifungal Agents

Journal of Fungi, Journal Year: 2022, Volume and Issue: 8(8), P. 857 - 857

Published: Aug. 16, 2022

Several new antifungals are currently in late-stage development, including those with novel pharmacodynamics/mechanisms of action that represent antifungal classes (manogepix, olorofim, ATI-2307, GR-2397). Others include agents within established or mechanisms similar to clinically available (ibrexafungerp, rezafungin, oteseconazole, opelconazole, MAT2203) have been modified order improve certain characteristics, enhanced pharmacokinetics and greater specificity for fungal targets. Many the under development also activity against Candida Aspergillus strains reduced susceptibility acquired resistance azoles echinocandins, whereas others demonstrate species intrinsically resistant most antifungals. The tolerability drug-drug interaction profiles these appear be promising, although number human subjects exposed many remains relatively small. Overall, potential expanding our armamentarium improving clinical outcomes patients invasive mycoses.

Language: Английский

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Update on therapeutic approaches for invasive fungal infections in adults

Therapeutic Advances in Infectious Disease, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 1, 2024

Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell transplant recipients but also patients malignancies or autoimmune diseases receiving immunomodulatory therapies, such as Bruton Tyrosine Kinase (BTK) inhibitor. Their attributable mortality remains elevated, part which is a contribution from globally emerging resistance in both molds yeasts. Because antifungal susceptibility test results often unavailable delayed, empiric tailored approaches choice agent(s) use combination therapy heterogeneous based on clinician experience knowledge host’s net state prior exposure, side effects interaction profile, clinical severity disease site(s) infection local data. In this review, we aim to summarize previous recommendations most recent literature treatment invasive mold yeast adults guide optimal evidence-based therapeutic approaches. We review data that support available agents, different triazoles have now been studied comparison previously preferred agents. discuss management complex specific fungi Scedosporium spp., Fusarium Trichosporon asahii, Candida auris. briefly explore newer agents formulations being investigated overcome pitfalls, limited olorofim, rezafungin, fosmanogepix, encochleated Amphotericin B. role surgical resection debridement, duration treatment, follow-up modalities, need for secondary prophylaxis, all remain challenging, especially chronically immunocompromised awaiting more immunosuppressive therapies.

Language: Английский

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Scedosporiosis and lomentosporiosis: modern perspectives on these difficult-to-treat rare mold infections

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

Published: March 29, 2024

SUMMARYAlthough

Language: Английский

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The antifungal pipeline for invasive fungal diseases: what does the future hold?

Expert Review of Anti-infective Therapy, Journal Year: 2023, Volume and Issue: 21(6), P. 577 - 594

Published: April 14, 2023

Over the last two decades, we have experienced pressing needs for new additions to antifungal armamentarium given emergence of resistant fungi, growth at-risk patient populations invasive fungal diseases (IFD), high morbidity and mortality associated with IFD.The current review will discuss five promising agents IFD (i.e. fosmanogepix, ibrexafungerp, olorofim, rezafungin, opelconazole), now in late-phase clinical studies, likely be available use near future. For each agent, describe its mechanism action, pharmacokinetic pharmacodynamic properties, spectrum activity as well safety efficacy data, including findings from ongoing trials. The potential roles these novel antifungals practice key considerations also discussed.There are unmet that should addressed future studies. These include defining their indications benefits, how best target them appropriately, surveillance stewardship use.

Language: Английский

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InvasiveScedosporiumandLomentospora prolificansInfections in Australia: A Multicenter Retrospective Cohort Study

Open Forum Infectious Diseases, Journal Year: 2023, Volume and Issue: 10(2)

Published: Feb. 1, 2023

Management of Scedosporium/Lomentospora prolificans infections remains challenging. We described predisposing factors, clinical manifestations, and outcomes these rare mold infections, including predictors early (1-month) late (18-month) all-cause mortality treatment failure.We conducted a retrospective Australian-based observational study proven/probable Scedosporium/L from 2005 to 2021. Data on patient comorbidities, treatment, up 18 months were collected. Treatment responses death causality adjudicated. Subgroup analyses, multivariable Cox regression, logistic regression performed.Of 61 infection episodes, 37 (60.7%) attributable L prolificans. Forty-five (73.8%) proven invasive fungal diseases (IFDs), 29 (47.5%) disseminated. Prolonged neutropenia receipt immunosuppressant agents documented in 27 (44.3%) 49 (80.3%) respectively. Voriconazole/terbinafine was administered 30 31 (96.8%) voriconazole alone prescribed for 15 24 (62.5%) Scedosporium spp infections. Adjunctive surgery performed episodes. Median time post-IFD diagnosis 9.0 days, only 22 (36.1%) attained success at months. Those who survived beyond 28 days antifungal therapy less immunosuppressed with fewer disseminated (both P < .001). Disseminated hematopoietic stem cell transplant associated increased rates. lower rates by 84.0% 72.0%, respectively, decreased odds 1-month failure 87.0%.Outcomes is poor, particularly or the highly population.

Language: Английский

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The Role of Olorofim in the Treatment of Filamentous Fungal Infections: A Review of In Vitro and In Vivo Studies

Journal of Fungi, Journal Year: 2024, Volume and Issue: 10(5), P. 345 - 345

Published: May 10, 2024

Invasive fungal infections have recently been recognized by the WHO as a major health, epidemiological, and economic issue. Their high mortality rates emergence of drug resistance driven development new molecules, including olorofim, an antifungal belonging to family compounds, orotomides. A review was conducted on PubMed database ClinicalTrials.gov website summarize microbiological profile olorofim its role in treatment filamentous infections. Twenty-four articles were included from search divided into two groups: “in vitro” group focusing minimum inhibitory concentration (MIC) results for various fungi vivo” evaluating pharmacokinetics (PK), pharmacodynamics (PD), efficacy, tolerability animal models infection humans. Olorofim demonstrated vitro vivo activity against numerous fungi, azole-resistant Aspergillus fumigatus, dermatophytes, endemic dimorphic fungi. showed higher MICs certain Fusarium species dematiaceous Alternaria alternata Exophiala dermatitidis; further studies are needed. Published PK-PD data humans limited. The ongoing phase III clinical trial eagerly awaited evaluate olorofim’s impact.

Language: Английский

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The epigenetic regulator Set9 harmonizes fungal development, secondary metabolism, and colonization capacity of Aspergillus flavus

International Journal of Food Microbiology, Journal Year: 2023, Volume and Issue: 403, P. 110298 - 110298

Published: June 22, 2023

Language: Английский

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