Use of voriconazole to predict susceptibility and resistance to isavuconazole for <i>Aspergillus fumigatus</i> using CLSI methods and interpretive criteria
Bibliographic record
Abstract
ABSTRACT Aspergillus fumigatus is a common cause of pulmonary and invasive mold infections among immunocompromised hosts. Mortality in immunocompromised hosts with invasive Aspergillus infections (IAI) has been reported to be as high as 80%. Therefore, appropriate therapy is essential in treating IAI. Both isavuconazole and voriconazole are first-line agents in treatment guidelines for IAI, but isavuconazole has favorable properties, often leading it to be preferred over voriconazole, given the lengthy duration of treatment. It is difficult to perform mold antifungal susceptibility testing, which often requires a reference lab and several weeks to determine results. Therefore, use of surrogate markers can be helpful to infer susceptibility when testing is not possible or delayed. We performed isavuconazole and voriconazole broth microdilution susceptibility testing by the Clinical and Laboratory Standards Institute (CLSI) method on a collection of 976 non-duplicate A. fumigatus isolates from a global surveillance program between 2017 and 2022. We found that voriconazole and isavuconazole have a very high essential agreement within two doubling dilutions at 99.9% and a categorical agreement of 92.7% with no very major errors, one major error (0.11%), and <10% minor errors. Many of the minor errors were in the setting of voriconazole testing at a MIC of 0.5 mg/L (susceptible) but isavuconazole at 2 mg/L (intermediate). Genetic analysis of cyp51 genes confirmed that isavuconazole and voriconazole susceptibility testing identified isolates with cyp51A and cyp51B mutations. Voriconazole can be used to predict the isavuconazole susceptibility testing result when A. fumigatus is tested by CLSI broth microdilution methodology.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.018 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".