<i>In vitro</i>assessment of CSA-131 and CSA-131 poloxamer form for the treatment of<i>Stenotrophomonas maltophilia</i>infections in cystic fibrosis
Bibliographic record
Abstract
BACKGROUND: Stenotrophomonas maltophilia is a Gram-negative bacterium resistant to several antibiotics and its prevalence in cystic fibrosis (CF) patients is increasing. OBJECTIVES: To evaluate the effects of ceragenins, non-peptide mimics of antimicrobial peptides, against both planktonic and biofilm forms of S. maltophilia and the cytotoxicity of ceragenins to the IB3-1 CF cell line. METHODS: Ceragenin CSA-131, with and without 5% Pluronic® F127 (a non-ionic amphiphilic poloxamer), and ceragenin CSA-13 were evaluated against S. maltophilia clinical isolates (n = 40). MICs and MBCs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1×, 2× and 4× MICs of ceragenins. The highest non-cytotoxic concentrations of ceragenins against IB3-1, a CF cell line, were determined by MTT assay. The effects of ceragenins against biofilm adhesion, formation and mature biofilms were investigated. RESULTS: CSA-131 with Pluronic® F127 displayed the lowest MICs (MIC50/MIC90: 1/2 mg/L) followed by CSA-131 (MIC50/MIC90: 2/4 mg/L), while those of CSA-13 were much higher (MIC50/MIC90: 16/32 mg/L). According to time-kill curve results, all concentrations at 4× MICs of ceragenins showed bactericidal activity (3 log reduction) after 4 h. While CSA-131 and CSA-131-poloxamer inhibited biofilm adhesion and formation by 87.74% and 83.42%, respectively, after 24 h, CSA-131 was more effective on mature biofilms. Formulating CSA-131 in poloxamer micelles did not affect the cytotoxicity of CSA-131 to IB3-1 cells. CONCLUSIONS: CSA-131 could be a potential antimicrobial agent for the treatment of S. maltophilia infections in CF, due to its low cytotoxicity on the CF cell line and good antimicrobial and antibiofilm effects.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".