Noncytotoxic polymyxin derivatives enhance antibiotic action against multidrug-resistant Gram-negative bacteria
Bibliographic record
Abstract
ABSTRACT The widespread emergence of multidrug-resistant (MDR) Gram-negative bacteria prompted the reintroduction of polymyxins in the clinic despite their adverse effects. Ongoing research is primarily focused on the development of non-nephrotoxic and -neurotoxic polymyxins as not only standalone agents but also as potentiators that enhance the activity of a partner antibiotic. Safer derivatives of polymyxin B 3 , a minor component of polymyxin B, were synthesized and utilized as a potentiator of multiple antibiotics. Compound 1 , consisting of Dap residues, was nontoxic to kidney cells and is a promising outer membrane permeabilizer that synergized with six different classes of antibiotics against MDR Gram-negative bacteria. Compound 1 extended the activity spectrum of rifampicin, zoliflodacin, and pristinamycin by lowering the minimum inhibitory concentrations of these antibiotics below their interpretative susceptibility breakpoints in MDR Pseudomonas aeruginosa , Acinetobacter baumannii , Escherichia coli , Klebsiella pneumoniae , and Enterobacter cloacae . Notably, the novel combination of zoliflodacin, a first-in-class antibiotic in phase III trials for gonorrhea, and compound 1 exhibited potent bactericidal activity in MDR P. aeruginosa and A. baumannii .
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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) | 0.002 | 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".