ArticlePloS one2012
Rapid evaluation in whole blood culture of regimens for XDR-TB containing PNU-100480 (sutezolid), TMC207, PA-824, SQ109, and pyrazinamide.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03941496 (Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy), which is not on this map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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.
Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Development and application of the direct mycobacterial growth inhibition assay: a systematic review.Frontiers in immunology · 2024Pooled it
- panTB-HM: a multi-arm clinical trial of a pan-TB regimen targeting both host and microbe.Trials · 2026Trial
- Trial
- A Narrative Review of Bedaquiline and Delamanid: New Arsenals Against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis.Journal of clinical laboratory analysis · 2024Review
- New Oxazolidinones for Tuberculosis: Are Novel Treatments on the Horizon?Pharmaceutics · 2024Review
- Delamanid or pretomanid? A Solomonic judgement!The Journal of antimicrobial chemotherapy · 2022Article
- Effects of Increasing Concentrations of Rifampicin on Different Mycobacterium tuberculosis Lineages in a Whole-Blood Bactericidal Activity Assay.Antimicrobial agents and chemotherapy · 2022Article
- Article
- Phenotypic and genomic comparison of Mycobacterium aurum and surrogate model species to Mycobacterium tuberculosis: implications for drug discovery.BMC genomics · 2017Article
- Spectinamides are effective partner agents for the treatment of tuberculosis in multiple mouse infection models.The Journal of antimicrobial chemotherapy · 2017Article
- Assessment of treatment response in tuberculosis.Expert review of respiratory medicine · 2016Review
- Immune activation of the host cell induces drug tolerance in Mycobacterium tuberculosis both in vitro and in vivo.The Journal of experimental medicine · 2016Article
- Activity of nitazoxanide and tizoxanide against Mycobacterium tuberculosis in vitro and in whole blood culture.Tuberculosis (Edinburgh, Scotland) · 2016Article
- Advances in Drug Discovery and Development for Pediatric Tuberculosis.Mini reviews in medicinal chemistry · 2016Review
- In silico-based high-throughput screen for discovery of novel combinations for tuberculosis treatment.Antimicrobial agents and chemotherapy · 2015Article
- Bedaquiline for the treatment of multidrug-resistant tuberculosis: great promise or disappointment?Therapeutic advances in chronic disease · 2015Review
- Tuberculosis treatment and drug regimens.Cold Spring Harbor perspectives in medicine · 2015Review
- Contribution of the nitroimidazoles PA-824 and TBA-354 to the activity of novel regimens in murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2015Article
- In vitro activity of AZD5847 against geographically diverse clinical isolates of Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2014Article
- Population pharmacokinetic/pharmacodynamic analysis of the bactericidal activities of sutezolid (PNU-100480) and its major metabolite against intracellular Mycobacterium tuberculosis in ex vivo whole-blood cultures of patients with pulmonary tuberculosis.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There presently is no rapid method to assess the bactericidal activity of new regimens for tuberculosis. This study examined PNU-100480, TMC207, PA-824, SQ109, and pyrazinamide, singly and in various combinations, against intracellular M. tuberculosis, using whole blood culture (WBA). The addition of 1,25-dihydroxy vitamin D facilitated detection of the activity of TMC207 in the 3-day cultures. Pyrazinamide failed to show significant activity against a PZA-resistant strain (M. bovis BCG), and was not further considered. Low, mid, and high therapeutic concentrations of each remaining drug were tested individually and in a paired checkerboard fashion. Observed bactericidal activity was compared to that predicted by the sum of the effects of individual drugs. Combinations of PNU-100480, TMC207, and SQ109 were fully additive, whereas those including PA-824 were less than additive or antagonistic. The cumulative activities of 2, 3, and 4 drug combinations were predicted based on the observed concentration-activity relationship, published pharmacokinetic data, and, for PNU-100480, published WBA data after oral dosing. The most active regimens, including PNU-100480, TMC207, and SQ109, were predicted to have cumulative activity comparable to standard TB therapy. Further testing of regimens including these compounds is warranted. Measurement of whole blood bactericidal activity can accelerate the development of novel TB regimens.
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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.