ArticleScientific reports2023
In vitro synergy screens of FDA-approved drugs reveal novel zidovudine- and azithromycin-based combinations with last-line antibiotics against Klebsiella pneumoniae.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 10 citations in OpenAlex.
- Combining Bile Salt with Gentamicin: A Promising Strategy Against Vibrio Parahaemolyticus and Escherichia Coli.Current microbiology · 2025Article
- Resensitizing the Untreatable: Zidovudine and Polymyxin Combinations to Combat Pan-Drug-ResistantPharmaceuticals (Basel, Switzerland) · 2025Article
- Penfluridol synergizes with colistin to reverse colistin resistance in Gram-negative bacilli.Scientific reports · 2025Article
- Impact of nafcillin and diosmin on the attachment, invasion, and stress survival of Salmonella Typhimurium.Scientific reports · 2025Article
- Metabolomics reveals the mechanisms of action of fosfomycin and azithromycin combination in the treatment ofFrontiers in cellular and infection microbiology · 2025Article
- Breaking the resistance: integrative approaches with novel therapeutics against Klebsiella pneumoniae.Archives of microbiology · 2024Review
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Authors and funding
5 authors at 3 institutions in 1 country.
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Abstract
Treatment of infections caused by multi-drug resistant (MDR) enterobacteria remains challenging due to the limited therapeutic options available. Drug repurposing could accelerate the development of new urgently needed successful interventions. This work aimed to identify and characterise novel drug combinations against Klebsiella pneumoniae based on the concepts of synergy and drug repurposing. We first performed a semi-qualitative high-throughput synergy screen (sHTSS) with tigecycline, colistin and fosfomycin (last-line antibiotics against MDR Enterobacteriaceae) against a FDA-library containing 1430 clinically approved drugs; a total of 109 compounds potentiated any of the last-line antibiotics. Selected hits were further validated by secondary checkerboard (CBA) and time-kill (TKA) assays, obtaining 15.09% and 65.85% confirmation rates, respectively. Accordingly, TKA were used for synergy classification based on determination of bactericidal activities at 8, 24 and 48 h, selecting 27 combinations against K. pneumoniae. Among them, zidovudine or azithromycin combinations with last-line antibiotics were further evaluated by TKA against a panel of 12 MDR/XDR K. pneumoniae strains, and their activities confronted with those clinical combinations currently used for MDR enterobacteria treatment; these combinations showed better bactericidal activities than usual treatments without added cytotoxicity. Our studies show that sHTSS paired to TKA are powerful tools for the identification and characterisation of novel synergistic drug combinations against K. pneumoniae. Further pre-clinical studies might support the translational potential of zidovudine- and azithromycin-based combinations for the treatment of these infections.
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