ArticleScientific reports2016
Repurposing clinically approved cephalosporins for tuberculosis therapy.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05169554 (Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy), which is not on this map. Cited by 51 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.
Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy: Comparison of 8 Weeks Standard Therapy (Rifampicin Plus Clarithromycin) vs. 4 Weeks Standard Plus Amoxicillin/Clavulanate Therapy [RC8 vs. RCA4]
Who cites it
51 citing papers in PubMed, 89 citations in OpenAlex.
- Early Bactericidal Activity of Meropenem plus Clavulanate (with or without Rifampin) for Tuberculosis: The COMRADE Randomized, Phase 2A Clinical Trial.American journal of respiratory and critical care medicine · 2022Trial
- Synthesis of 4-Aminoindole-Containing Cephalosporin Prodrugs and Their Biological Activity againstACS infectious diseases · 2026Article
- Cefpiramide RestrictsACS medicinal chemistry letters · 2026Article
- Genetic interference of distinctive Mycobacterium tuberculosis peptidoglycan modifications enhances β-lactam susceptibility and reveals expression-sensitive host immune dynamics.Scientific reports · 2026Article
- The ribosomal RNA synthesis ratio biomarker in Mycobacterium ulcerans for drug activity evaluation.Infectious diseases of poverty · 2026Article
- Assessing the efficacy of combined treatment using bedaquiline against clinical isolates of multidrug-resistant Mycobacterium tuberculosis in vitro and the macrophage model.BMC microbiology · 2026Article
- Epetraborole pharmacokinetics/pharmacodynamics in the hollow fiber system model ofAntimicrobial agents and chemotherapy · 2025Article
- Mycobacteria susceptibility to epetraborole: how far can it go?The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2025Article
- Prospects of Inhalable Formulations of Conventionally Administered Repurposed Drugs for Adjunctive Treatment of Drug-Resistant Tuberculosis: Supporting Evidence from Clinical Trials and Cohort Studies.Journal of aerosol medicine and pulmonary drug delivery · 2025Review
- Beta-lactam combination treatment overcomes rifampicin resistance in Mycobacterium tuberculosis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Sanfetrinem, an oral β-lactam antibiotic repurposed for the treatment of tuberculosis.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Article
- Addressing urgent priorities in antibiotic development: insights from WHO 2023 antibacterial clinical pipeline analyses.The Lancet. Microbe · 2025Review
- Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.Molecular cancer · 2024Article
- Sanfetrinem, an oral β-lactam antibiotic repurposed for the treatment of tuberculosis.bioRxiv : the preprint server for biology · 2024Article
- Amoxicillin/clavulanate in combination with rifampicin/clarithromycin is bactericidal against Mycobacterium ulcerans.PLoS neglected tropical diseases · 2024Article
- In vitro synergy screens of FDA-approved drugs reveal novel zidovudine- and azithromycin-based combinations with last-line antibiotics against Klebsiella pneumoniae.Scientific reports · 2023Article
- Potential Repurposed Drug Candidates for Tuberculosis Treatment: Progress and Update of Drugs Identified in Over a Decade.ACS omega · 2023Review
- Mutations inmBio · 2023Article
- Repurposing β-Lactams for the Treatment ofAntibiotics (Basel, Switzerland) · 2023Article
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While modern cephalosporins developed for broad spectrum antibacterial activities have never been pursued for tuberculosis (TB) therapy, we identified first generation cephalosporins having clinically relevant inhibitory concentrations, both alone and in synergistic drug combinations. Common chemical patterns required for activity against Mycobacterium tuberculosis were identified using structure-activity relationships (SAR) studies. Numerous cephalosporins were synergistic with rifampicin, the cornerstone drug for TB therapy, and ethambutol, a first-line anti-TB drug. Synergy was observed even under intracellular growth conditions where beta-lactams typically have limited activities. Cephalosporins and rifampicin were 4- to 64-fold more active in combination than either drug alone; however, limited synergy was observed with rifapentine or rifabutin. Clavulanate was a key synergistic partner in triple combinations. Cephalosporins (and other beta-lactams) together with clavulanate rescued the activity of rifampicin against a rifampicin resistant strain. Synergy was not due exclusively to increased rifampicin accumulation within the mycobacterial cells. Cephalosporins were also synergistic with new anti-TB drugs such as bedaquiline and delamanid. Studies will be needed to validate their in vivo activities. However, the fact that cephalosporins are orally bioavailable with good safety profiles, together with their anti-mycobacterial activities reported here, suggest that they could be repurposed within new combinatorial TB therapies.
Identifiers
What OpenQuestion holds
Registered trials
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.