Polymyxin B<sub>3</sub>–Tobramycin Hybrids with <i>Pseudomonas aeruginosa</i>-Selective Antibacterial Activity and Strong Potentiation of Rifampicin, Minocycline, and Vancomycin
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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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 | 0.000 | 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) | 0.001 | 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".