ArticleThe Journal of antimicrobial chemotherapy2025
Physiologically informed in vitro framework reveals context-dependent combinatory activity of niclosamide-colistin against Gram-negative bacteria.
Article in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Chitosan Stabilizes Curcumin against Hydrolysis and Potentiates Antimicrobial Activity againstACS omega · 2026Article
- Colistin-stabilized antisolvent precipitation enables engineering of microcrystalline niclosamide for inhalable composite powders.International journal of pharmaceutics · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
backgroundSynergy between antibiotic pairs is typically discovered using chequerboard assays that assume uniform, static drug exposure; however, such conditions rarely apply in vivo. Dynamic and heterogeneous tissue environments create spatial and temporal mismatches in drug exposure that can uncouple synergistic interactions, leading to unexpected treatment failure.
objectiveThis study aims to develop a physiologically relevant in vitro model that integrates infection-site microenvironments and drug-specific pharmacokinetics. This platform was applied to investigate how spatial and temporal factors affect antibiotic synergy, using niclosamide and colistin as a case study for inhaled delivery to infected lung airways.
methodsOpportunistic Gram-negative bacterial species with varied susceptibility to niclosamide and colistin were tested. Synergy was assessed using microdilution chequerboard assays under both standard and physiologically altered conditions. In vitro models incorporating mucus interactions and pharmacokinetic parameters were used to examine the effects of spatial and temporal decoupling on the activity of the combination.
resultsChanges in pH and cation concentration altered both individual drug potency and combination effects, consistent with the ionizable nature of niclosamide and membrane-stabilizing roles of divalent cations. Simulated rapid clearance of niclosamide reduced its contribution to synergy, suggesting that the combined effects are time-sensitive. Mucin impaired niclosamide diffusion and diminished combination efficacy, indicating that spatial separation can disrupt synergistic interactions.
conclusionsMicroenvironmental complexity and drug kinetics significantly influence antibiotic synergy. Incorporating physiologically relevant spatial and temporal variables into in vitro models may improve clinical prediction and guide rational design of combination therapies.
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