SynthesisAntimicrobial agents and chemotherapy2021
Lesion Penetration and Activity Limit the Utility of Second-Line Injectable Agents in Pulmonary Tuberculosis.
Synthesis in Antimicrobial agents and chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled 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.
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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Studying intrapulmonary pharmacokinetics for tuberculosis treatment: a systematic review of methodology.The Journal of antimicrobial chemotherapy · 2025Pooled it
- The Kinetics of Bedaquiline Diffusion in Tuberculous Cavities Open a Window for the Emergence of Resistance.The Journal of infectious diseases · 2025Article
- Rankings of tuberculosis antibiotic treatment regimens are sensitive to spatial scale, detection limit, and initial host bacterial burden.Journal of theoretical biology · 2025Article
- Evolution of Small Molecule Inhibitors ofJournal of medicinal chemistry · 2025Article
- Targeted delivery of antitubercular drugs using glucan lipid particles.Microbiology spectrum · 2025Article
- A Physiologically Relevant In Vitro Model of Nonreplicating Persistent Mycobacterium tuberculosis in Caseum.Current protocols · 2025Article
- The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis.Nature communications · 2025Article
- Leveraging insights from cancer to improve tuberculosis therapy.Trends in molecular medicine · 2025Article
- Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Role of DNA Double-Strand Break Formation in Gyrase Inhibitor-Mediated Killing of Nonreplicating PersistentACS infectious diseases · 2024Article
- Normalizing granuloma vasculature and matrix improves drug delivery and reduces bacterial burden in tuberculosis-infected rabbits.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- stormTB: a web-based simulator of a murine minimal-PBPK model for anti-tuberculosis treatments.Frontiers in pharmacology · 2024Article
- Lung microenvironments harborAntimicrobial agents and chemotherapy · 2023Article
- ADP-ribosylation-resistant rifabutin analogs show improved bactericidal activity against drug-tolerantAntimicrobial agents and chemotherapy · 2023Article
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- A minimal PBPK model to accelerate preclinical development of drugs against tuberculosis.Frontiers in pharmacology · 2023Article
- Advances in the design of combination therapies for the treatment of tuberculosis.Expert opinion on drug discovery · 2023Review
- Pharmacodynamics and Bactericidal Activity of Combination Regimens in Pulmonary Tuberculosis: Application to Bedaquiline-Pretomanid-Pyrazinamide.Antimicrobial agents and chemotherapy · 2022Article
- Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment.The European respiratory journal · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Amikacin and kanamycin are second-line injectables used in the treatment of multidrug-resistant tuberculosis (MDR-TB) based on the clinical utility of streptomycin, another aminoglycoside and first-line anti-TB drug. While streptomycin was tested as a single agent in the first controlled TB clinical trial, introduction of amikacin and kanamycin into MDR-TB regimens was not preceded by randomized controlled trials. A recent large retrospective meta-analysis revealed that compared with regimens without any injectable drug, amikacin provided modest benefits, and kanamycin was associated with worse outcomes. Although their long-term use can cause irreversible ototoxicity, they remain part of MDR-TB regimens because they have a role in preventing emergence of resistance to other drugs. To quantify the contribution of amikacin and kanamycin to second-line regimens, we applied two-dimensional matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging in large lung lesions, quantified drug exposure in lung and in lesions of rabbits with active TB, and measured the concentrations required to kill or inhibit growth of the resident bacterial populations. Using these metrics, we applied site-of-action pharmacokinetic and pharmacodynamic (PK-PD) concepts and simulated drug coverage in patients' lung lesions. The results provide a pharmacological explanation for the limited clinical utility of both agents and reveal better PK-PD lesion coverage for amikacin than kanamycin, consistent with retrospective data of contribution to treatment success. Together with recent mechanistic studies dissecting antibacterial activity from aminoglycoside ototoxicity, the limited but rapid penetration of streptomycin, amikacin, and kanamycin to the sites of TB disease supports the development of analogs with improved efficacy and tolerability.
Indexed as
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.