ArticleThe Journal of antimicrobial chemotherapy2017
Spectinamides are effective partner agents for the treatment of tuberculosis in multiple mouse infection models.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Sterilizing activity of spectinamide MBX-4888A when replacing linezolid in the Nix-TB regimen in the relapsing BALB/c mouse model of tuberculosis.Antimicrobial agents and chemotherapy · 2025Article
- Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon.Acta pharmaceutica Sinica. B · 2025Review
- Assessment of tuberculosis drug efficacy using preclinical animal models and in vitro predictive techniques.npj antimicrobials and resistance · 2024Article
- Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Enhancing the therapeutic window for Spectinamide anti-tuberculosis Agents: Synthesis, Evaluation, and activation of phosphate prodrug 3408.Bioorganic & medicinal chemistry letters · 2024Article
- A modified BPaL regimen for tuberculosis treatment replaces linezolid with inhaled spectinamides.eLife · 2024Article
- Therapeutic developments for tuberculosis and nontuberculous mycobacterial lung disease.Nature reviews. Drug discovery · 2024Review
- Development of 2nd generation aminomethyl spectinomycins that overcome native efflux inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Development of a Minimalistic Physiologically Based Pharmacokinetic (mPBPK) Model for the Preclinical Development of Spectinamide Antibiotics.Pharmaceutics · 2023Article
- Developing synergistic drug combinations to restore antibiotic sensitivity in drug-resistantAntimicrobial agents and chemotherapy · 2023Article
- Characterization of spectinamide 1599 efficacy against different mycobacterial phenotypes.Tuberculosis (Edinburgh, Scotland) · 2023Article
- Spatial relationships of intra-lesion heterogeneity in Mycobacterium tuberculosis microenvironment, replication status, and drug efficacy.PLoS pathogens · 2022Article
- Systematic measurement of combination-drug landscapes to predict in vivo treatment outcomes for tuberculosis.Cell systems · 2021Article
- Model-Based Exposure-Response Assessment for Spectinamide 1810 in a Mouse Model of Tuberculosis.Antimicrobial agents and chemotherapy · 2021Article
- Comparative Analysis of Pharmacodynamics in the C3HeB/FeJ Mouse Tuberculosis Model for DprE1 Inhibitors TBA-7371, PBTZ169, and OPC-167832.Antimicrobial agents and chemotherapy · 2021Article
- Preclinical Evaluation of Inhalational Spectinamide-1599 Therapy against Tuberculosis.ACS infectious diseases · 2021Article
- Replacement of S14 Protein in Ribosomes of Zinc-Starved Mycobacteria Reduces Spectinamide Sensitivity.Antimicrobial agents and chemotherapy · 2021Article
- The quest for the holy grail: new antitubercular chemical entities, targets and strategies.Drug discovery today · 2020Review
- Identification of Anti-tuberculosis Compounds From Aurone Analogs.Frontiers in microbiology · 2020Article
- New Drugs for the Treatment of Tuberculosis.Clinics in chest medicine · 2019Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Objectives: New drug regimens employing combinations of existing and experimental antimicrobial agents are needed to shorten treatment of tuberculosis (TB) in humans. The spectinamides are narrow-spectrum semisynthetic analogues of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis . Spectinamides, including lead 1599, have been previously shown to exhibit a promising therapeutic profile in mice as single agents. Here we explore the in vivo activity of lead spectinamides when combined with other agents. Methods: The efficacy of 1599 or 1810 was tested in combination in three increasingly advanced TB mouse models. Mice were infected by aerosol and allowed to establish acute or chronic infection, followed by treatment (≤4 weeks) with the spectinamides alone or in two- and three-drug combination regimens with existing and novel therapeutic agents. Bacteria were enumerated from lungs by plating for cfu. Results: Herein we show the following: (i) 1599 exhibits additive or synergistic activity with most of the first-line agents; (ii) 1599 in combination with rifampicin and pyrazinamide or with bedaquiline and pyrazinamide promotes significantly improved efficacy in the high-dose aerosol model; (iii) 1599 enhances efficacy of rifampicin or pyrazinamide in chronically infected BALB/c mice; and (iv) 1599 is synergistic when administered in combination with rifampicin and pyrazinamide in the C3HeB/FeJ mouse model showing caseous necrotic pulmonary lesions. Conclusions: Spectinamides were effective partner agents for multiple anti-TB agents including bedaquiline, rifampicin and pyrazinamide. None of these in vivo synergistic interactions was predicted from in vitro MIC chequerboard assays. These data support further development of the spectinamides as combination partners with existing and experimental anti-TB agents.
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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.