In vitro activity of olorofim against Aspergillus fumigatus sensu lato clinical isolates: activity is retained against isolates showing resistance to azoles and/or amphotericin B

Escribano, Pilar; Gómez, Ana; Reigadas, Elena; Muñóz, Patricia; Guinea, Jesús; Sánchez-Yebra, Waldo; Lozano, Irene Iglesias; Marfil, Eduardo; Rosa, Montserrat Muñoz de la; García, Rocio Tejero; Cobo, Fernando; Castro, Carmen; López, Concepción; Rezusta, Antonio; Peláez, Teresa; Serra, Julia Lozano; Jiménez, Rosa María Rodríguez; Echeverría, Cristina Labayru; Pérez, Cristina Losa; Megías-Lobón, Gregoria; Lorenzo, Belén Huerta; Sánchez-Reus, Ferran; Ayats, Josefina; Martín, María Teresa; Vidal, Inmaculada; Sánchez-Hellín, Victoria; Ibáñez, Elisa; Valentín, Amparo; Pemán, J; Fajardo, Miguel; Pazos, Carmen; Rodríguez-Mayo, María; Pérez‐Ayala, Ana; Gómez, Elia; Serrano, Julia; Rodríguez, Belén; Zvezdanova, Estreya; Díaz-García, Judith; Núñez, Ana; Machado, Marina; Sánchez-Romero, Isabel; García-Rodríguez, Julio; Pozo, José Luís del; Vallejo, Manuel Rubio; Puig, Carlos Ruiz de Alegría; López-Soria, Leyre; Marimón, José María; Fernández-Torres, Marina; Hernáez-Crespo, Silvia

doi:10.1016/j.cmi.2022.05.013

Cited by 10 publications

(5 citation statements)

References 12 publications

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“…Olorofim displays high in vitro activity against A. fumigatus isolates (n=332), with MICs ranging from 0.008 to 0.125 mg/L, and was not impacted by the presence of resistance to other antifungals, including either azoles or amphotericin B. 169 Against 160 other invasive moulds, including Microascus/Scopulariopsis, Rasamsonia, Penicillium and Talaromyces species, olorofim activity was observed, again, irrespective of resistance to other antifungals. 170…”

Section: Olorofimmentioning

confidence: 87%

Antifungal resistance, combinations and pipeline: oh my!

Stover,

Hawkins,

Keck

et al. 2023

DIC

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Invasive fungal infections are a strong contributor to healthcare costs, morbidity and mortality, especially amongst hospitalized patients. Historically, Candida was responsible for approximately 15% of all nosocomial bloodstream infections. In the past 10 years, the epidemiology of Candida species has altered, with increasing prevalence of resistant species. With rising fungal resistance, especially in Candida spp., the demand for novel antifungal therapies has exponentially increased over the last decade. Newer antifungal agents have become an attractive option for patients needing long-term therapy for infections or those requiring antifungal prophylaxis. Despite advances in coverage of non-Candida pathogens with newer agents, clinical scenarios involving multidrug-resistant fungal pathogens continue to arise in practice. Combination antifungal therapy can lead to a host of side-effects, some of which can be drug limiting. Additional antifungal therapies with enhanced fungal spectrum of activity and decreased rates of adverse effects are warranted. Fosmanogepix, ibrexafungerp, olorofim and rezafungin may help fill some of these gaps in the antifungal armamentarium.This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/ challenges-and-strategies-in-the-managementof-invasive-fungal-infections

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Section: Olorofimmentioning

confidence: 87%

Antifungal resistance, combinations and pipeline: oh my!

Stover,

Hawkins,

Keck

et al. 2023

DIC

View full text Add to dashboard Cite

show abstract

“…In areas known to have a high prevalence of environmental Aspergillus resistance (> 10%), treatment should be started as described above. Olorofim, one of several new antifungal agents currently in development, retains excellent activity against azole-resistant Aspergillus [ 73 ].…”

Section: Treatmentmentioning

confidence: 99%

Invasive Mold Infections in Children: Navigating Troubled Waters with a Broken Compass

2023

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Incidence of invasive mold infections in children, while rare, is increasing as the population of high-risk patients expands, including premature infants, pediatric patients undergoing treatment for hematological malignancies, or recipients of allogeneic hematologic stem cell transplants. The infectious agents, including Aspergillus spp., Mucorales, and other molds, are especially difficult to treat and have serious morbidity and high mortality. Clinicians must maintain a high index of suspicion for invasive mold infections in at-risk patients. Diagnosis of invasive mold infections is complicated by difficulties isolating pathogens on culture, but progress is being made in immunological and molecular diagnostic technologies. Treatment in children is challenging; no randomized controlled trials exist. There is a growing body of data on treatment, specifically on safer antifungal agents, including indications for treatment, spectrum of coverage, pharmacokinetics for different ages, and pharmacodynamic targets associated with therapeutic success. However, pediatricians must often extrapolate from adult data. In this review, we aim to harmonize the existing body of literature on invasive mold infections in children, covering epidemiology, clinical presentations, diagnostic methods, and principles of management.

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“… 123 This drug is a potential anti- Aspergillus candidate, being active against azole resistant strains. 28 , 113 , 124 − 126 Olorofim also presents activity at relatively low MICs against L. prolificans and species of Scedosporium , 127 Histoplasma , Blastomyces , and Coccidioides . 28 , 128 The drug is also active against dermatophytes species such as Trichophyton spp., Epidermophyton spp., and Microsporum spp.…”

Section: Antifungals Under Developmentmentioning

confidence: 99%

“…Olorofim interrupts pyrimidine synthesis by inhibiting the enzyme dihydroorotate dehydrogenase. , Dihydroorotate dehydrogenase participates in the de novo pyrimidine biosynthesis pathway, which is required for DNA, RNA, protein, and cell wall syntheses . This drug is a potential anti- Aspergillus candidate, being active against azole resistant strains. ,,− Olorofim also presents activity at relatively low MICs against L. prolificans and species of Scedosporium , Histoplasma , Blastomyces , and Coccidioides . , The drug is also active against dermatophytes species such as Trichophyton spp., Epidermophyton spp., and Microsporum spp . Olorofim lacks activity against Candida , Cryptococcus , and Mucorales species.…”

Section: Antifungals Under Developmentmentioning

confidence: 99%