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Record W4390740053 · doi:10.1128/aac.01132-23

<i>In vitro</i> activity of manogepix and comparators against infrequently encountered yeast and mold isolates from the SENTRY Surveillance Program (2017–2022)

2024· article· en· W4390740053 on OpenAlexfundno aff
Michael A. Pfaller, Michael D. Huband, Paul Bien, Cecília G Carvalhaes, Abby L Klauer, Mariana Castanheira

Bibliographic record

VenueAntimicrobial Agents and Chemotherapy · 2024
Typearticle
Languageen
FieldMedicine
TopicAntifungal resistance and susceptibility
Canadian institutionsnot available
FundersbioMérieuxIdorsia PharmaceuticalsTenNor TherapeuticsAstellas Foundation for Research on Metabolic DisordersShionogiBasilea PharmaceuticaAstellas PharmaPfizerMelinta TherapeuticsEntasis TherapeuticsU.S. Food and Drug AdministrationAmplyxRoivant SciencesNabriva TherapeuticsAlbany College of Pharmacy and Health SciencesBDGenePOCUniversity of North TexasBoston PharmaceuticalsF. Hoffmann-La RocheNovartisHarvard UniversityWockhardtAllerganCidara TherapeuticsUniversity of Southern CaliforniaBayer
KeywordsMicrobiologyCandida kruseiBiologyRhodotorulaPaecilomycesAmphotericin BFungi imperfectiYeastCandida albicansCandida tropicalisAntifungalBotanyBiochemistry

Abstract

fetched live from OpenAlex

ABSTRACT Manogepix is a potent new antifungal agent targeting the fungal Gwt1 enzyme. Manogepix has previously demonstrated potent in vitro activity against clinical isolates of both Candida (except Candida krusei ) and Aspergillus species. This study determined the in vitro activity of manogepix and comparators against a large collection of infrequently encountered yeast and molds. Manogepix demonstrated potent in vitro activity against infrequently encountered yeasts exhibiting elevated MIC values to other drug classes, including Candida spp. (MIC 50/90 , 0.008/0.12 mg/L), Saprochaete clavata ( Magnusiomyces clavatus ) (MIC 50/90 , 0.03/0.06 mg/L), Magnusiomyces capitatus (MIC range , 0.016-0.06 mg/L), Rhodotorula minuta (MIC, 0.016 mg/L), and Rhodotorula mucilaginosa (MIC 50/90 , 0.03/0.12 mg/L). Similarly, manogepix was active against infrequently encountered mold isolates and strains exhibiting elevated MIC/MEC values to echinocandins, azoles, and amphotericin B, including Coprinopsis cinerea (MEC, 0.004 mg/L), Fusarium spp. (MEC 50/90 , 0.016/0.06 mg/L), Fusarium ( Gibberella ) fujikuroi species complex (MEC 50/90 , 0.016/0.03 mg/L), Lomentospora prolificans (MEC 50/90 , 0.03/0.06 mg/L), Microascus cirrosus (MEC, 0.008 mg/L), Paecilomyces spp. (MEC 50/90 , ≤0.008/0.016 mg/L), Pleurostomophora richardsiae (MEC, 0.06 mg/L), Sarocladium kiliense (MEC range, 0.016–0.12 mg/L), and Scedosporium spp. (MEC 50/90 , 0.03/0.06 mg/L). Manogepix demonstrated potent activity against a majority of the infrequently encountered yeast and mold isolates tested including strains with elevated MIC/MEC values to other drug classes. Additional clinical development of manogepix (fosmanogepix) in difficult-to-treat, resistant fungal infections is warranted.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.278
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations22
Published2024
Admission routes1
Has abstractyes

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