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Record W4387541094 · doi:10.1021/acsinfecdis.3c00189

Small-Molecule Antibiotic Drug Development: Need and Challenges

2023· review· en· W4387541094 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueACS Infectious Diseases · 2023
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAntibiotic Resistance in Bacteria
Canadian institutionsDiscovery Centre
FundersMedical Research CouncilUK Research and InnovationDiabetes UKDepartment for Business, Energy and Industrial Strategy, UK GovernmentAcademy of Medical SciencesBritish Heart FoundationWellcome Trust
KeywordsAntibioticsContext (archaeology)Intensive care medicineDrug developmentAntibiotic resistancePopulationDrugMedicineBiologyEnvironmental healthPharmacologyMicrobiology

Abstract

fetched live from OpenAlex

The need for new antibiotics is urgent. Antimicrobial resistance is rising, although currently, many more people die from drug-sensitive bacterial infections. The continued evolution of drug resistance is inevitable, fueled by pathogen population size and exposure to antibiotics. Additionally, opportunistic pathogens will always pose a threat to vulnerable patients whose immune systems cannot efficiently fight them even if they are sensitive to available antibiotics, according to clinical microbiology tests. These problems are intertwined and will worsen as human populations age, increase in density, and experience disruptions such as war, extreme weather events, or declines in standard of living. The development of appropriate drugs to treat all the world's bacterial infections should be a priority, and future success will likely require combinations of multiple approaches. However, the highest burden of bacterial infection is in Low- and Middle-Income Countries, where limited medical infrastructure is a major challenge. For effectively managing infections in these contexts, small-molecule-based treatments offer significant advantages. Unfortunately, support for ongoing small-molecule antibiotic discovery has recently suffered from significant challenges related both to the scientific difficulties in treating bacterial infections and to market barriers. Nevertheless, small-molecule antibiotics remain essential and irreplaceable tools for fighting infections, and efforts to develop novel and improved versions deserve ongoing investment. Here, we first describe the global historical context of antibiotic treatment and then highlight some of the challenges surrounding small-molecule development and potential solutions. Many of these challenges are likely to be common to all modalities of antibacterial treatment and should be addressed directly.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.990
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
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)0.0000.000

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 head0.043
GPT teacher head0.287
Teacher spread0.244 · 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