Polymyxin B<sub>3</sub>–Tobramycin Hybrids with <i>Pseudomonas aeruginosa</i>-Selective Antibacterial Activity and Strong Potentiation of Rifampicin, Minocycline, and Vancomycin
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.
Bibliographic record
Abstract
There is an urgent need to develop novel antibacterial agents able to eradicate drug-resistant Gram-negative pathogens such as Pseudomonas aeruginosa . Antimicrobial hybrids have emerged as a promising strategy to combat bacterial resistance, as a stand-alone drug but also as an adjuvant in combination with existing antibiotics. Herein, we report for the first time the synthesis and biological evaluation of polymyxin-aminoglycoside heterodimers composed of polymyxin B 3 covalently linked to tobramycin via an aliphatic hydrocarbon linker. The polymyxin B 3 –tobramycin hybrids demonstrate potent activity against carbapenem-resistant as well as multidrug- or extensively drug-resistant (MDR/XDR) P. aeruginosa clinical isolates. Furthermore, the most potent hybrid was able to synergize with currently used antibiotics against wild-type and MDR/XDR P. aeruginosa but also against Acinetobacter baumannii as well. The promising biological activity described herein warrants additional studies into design and development of new antimicrobial hybrids able to surmount the problem of antimicrobial resistance.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it