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Record W4317878767 · doi:10.1101/2023.01.23.22283996

Personalized Inhaled Bacteriophage Therapy Decreases Multidrug-Resistant <i>Pseudomonas aeruginosa</i>

2023· preprint· en· W4317878767 on OpenAlexaff
BK Chan, GL Stanley, KE Kortright, Meera Modak, IM Ott, Ying Sun, Silvia Würstle, C. Grun, Bernd Kazmierczak, Govindarajan Rajagopalan, Z. Leah Harris, CJ Britto, James D. Stewart, JS Talwalkar, Casey R. Appell, Nauman Chaudary, SK Jagpal, Raksha Jain, Adaobi Kanu, BS Quon, JM Reynolds, QA Mai, Veronika Shabanova, PE Turner, Jonathan L. Koff

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldEnvironmental Science
TopicBacteriophages and microbial interactions
Canadian institutionsUniversity of British Columbia
FundersNational Institutes of HealthUniversity of PittsburghTexas Tech UniversityYale Center for Clinical Investigation, Yale School of MedicineYale University
KeywordsPseudomonas aeruginosaPhage therapyBacteriophageLytic cycleAntibiotic resistanceMicrobiologySputumVirulenceCystic fibrosisAntibioticsBacteriaAntimicrobialMultiple drug resistanceBiologyVirologyMedicineVirusEscherichia coliTuberculosisInternal medicineGeneGeneticsPathology

Abstract

fetched live from OpenAlex

Abstract Bacteriophage therapy, which uses lytic viruses as antimicrobials, has received renewed interest to address the emerging antimicrobial resistance (AMR) crisis. Cystic fibrosis (CF), a disease complicated by recurrent P. aeruginosa pulmonary infections that cause lung function decline, is an example where AMR is already a clinical problem. While bacteria evolve bacteriophage resistance, we developed a strategy to select bacteriophages that target bacterial cell surface receptors that contribute to antibiotic resistance or virulence. Thus, in addition to killing bacteria, these phages steer surviving, evolved bacteria to antibiotic re-sensitivity or attenuated virulence. Here, we present outcomes from nine CF adults treated with nebulized bacteriophage therapy for AMR P. aeruginosa using this personalized approach. Results showed that phage therapy: 1) reduced sputum P. aeruginosa , 2) showed evidence for predicted trade-offs in most subjects, and 3) improved lung function, which may reflect the combined effects of decreased bacterial sputum density and phage-driven evolved trade-offs.

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)0.000
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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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)0.0020.000

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 head0.034
GPT teacher head0.271
Teacher spread0.238 · 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

Citations18
Published2023
Admission routes1
Has abstractyes

Explore more

Same venuemedRxivSame topicBacteriophages and microbial interactionsFrench-language works237,207