Evidence map›Paper›PMID 39688409›Full record

ArticleThe Journal of antimicrobial chemotherapy2025

Repurposing zidovudine and 5-fluoro-2'-deoxyuridine as antibiotic drugs made possible by synergy with both trimethoprim and the mitochondrial toxicity-reducing agent uridine.

Jolanta J Levenfors, Joakim Bjerketorp, Bengt Guss, Christina Nord, Sha Cao, Diarmaid Hughes, Anders Broberg, Bo Öberg

Abstract read
In one paragraph

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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Jolanta J LevenforsDepartment of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Joakim BjerketorpDepartment of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Bengt GussDepartment of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Christina NordDepartment of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Sha CaoDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID 0000-0003-3033-9219
Diarmaid HughesDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-7456-9182
Anders BrobergDepartment of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.ORCID 0000-0003-2581-8047
Bo ÖbergUltupharma AB, Södra Rudbecksgatan 13, Uppsala SE-752 36, Sweden.

Funding

Swedish Research Council 2021-04814Ultupharma AB
6 · The paper itself

Abstract

objectivesThe increasing frequency of antibiotic-resistant bacterial infections is a major public health challenge, and new antibiotic drugs are urgently needed. A rapid solution to the problem is to repurpose clinically approved compounds with antibacterial properties, such as the nucleoside analogues zidovudine (azidothymidine) or 5-fluoro-2'-deoxyuridine. Here we report the in vitro and in vivo antibacterial properties of double and triple combinations of azidothymidine or 5-fluoro-2'-deoxyuridine with uridine and/or trimethoprim.

methodsWe determined MICs of azidothymidine and 5-fluoro-2'-deoxyuridine, alone or combined with uridine and/or trimethoprim, against a selection of Gram-negative and Gram-positive bacteria. We also measured MICs of a selection of antibiotics of different classes as a function of uridine concentration. The efficacy of azidothymidine and 5-fluoro-2'-deoxyuridine with uridine and/or trimethoprim was measured in a murine peritonitis infection model.

resultsThe addition of uridine enhanced the in vitro antibacterial activity of azidothymidine and 5-fluoro-2'-deoxyuridine, against Gram-negative and Gram-positive bacteria, respectively. Uridine also enhanced the in vitro antibacterial activity of azidothymidine/trimethoprim and 5-fluoro-2'-deoxyuridine/trimethoprim combinations. Triple combinations containing azidothymidine, trimethoprim and uridine, showed antibacterial synergy against Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) whereas the 5-fluoro-2'-deoxyuridine, trimethoprim and uridine combination showed synergy against the Gram-positive Staphylococcus aureus. The positive effect of uridine on the efficacy of azidothymidine/trimethoprim combination was also observed in vivo in a murine E. coli peritonitis model.

conclusionsTriple combinations of these clinically approved compounds warrant further investigations as therapies to combat antibiotic-resistant infections.

Indexed as

Anti-Bacterial AgentsDrug RepositioningDrug SynergismTrimethoprimUridineZidovudineAnimalsDisease Models, AnimalDrug Therapy, CombinationFemaleGram-Negative BacteriaGram-Positive BacteriaMiceMicrobial Sensitivity TestsPeritonitisTreatment OutcomeAnti-Bacterial AgentsTrimethoprimUridineZidovudine

Identifiers

PMID39688409
PMCPMC11787897

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LicenceCC BY-NC
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.