ArticleAntimicrobial agents and chemotherapy2014
Redefining multidrug-resistant tuberculosis based on clinical response to combination therapy.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04062201 (An Open Label, Randomized Controlled Trial to Establish the Efficacy and Safety of a Study Strategy Consisting of 6 Months of Bedaquiline), which is not on this map. Cited by 36 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.
An Open Label, Randomized Controlled Trial to Establish the Efficacy and Safety of a Study Strategy Consisting of 6 Months of Bedaquiline (BDQ), Delamanid (DLM), and Linezolid (LNZ), With Levofloxacin (LVX) and Clofazimine (CFZ) Compared to the Current South African Standard of Care (Control Strategy) for 9 Months for the Treatment of Rifampicin Resistant Tuberculosis (RR-TB)
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2020Pooled it
- Artificial intelligence-derived 3-Way Concentration-dependent Antagonism of Gatifloxacin, Pyrazinamide, and Rifampicin During Treatment of Pulmonary Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Trial
- Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis. A Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2018Trial
- Imipenem Pharmacokinetics/Pharmacodynamics in Preclinical Hollow Fiber Model, Dose Finding in Virtual Patients, and Clinical Evidence of Efficacy for Mycobacterium abscessus Lung Disease.The Journal of infectious diseases · 2025Article
- Determining the Delamanid Pharmacokinetics/Pharmacodynamics Susceptibility Breakpoint Using Monte Carlo Experiments.Antimicrobial agents and chemotherapy · 2023Article
- The evolution of antibiotic resistance in an incurable and ultimately fatal infection: A retrospective case study.Evolution, medicine, and public health · 2023Article
- 6-Bromo-2-naphthol from Silene armeria extract sensitizes Acinetobacter baumannii strains to polymyxin.Scientific reports · 2022Article
- Minocycline intra-bacterial pharmacokinetic hysteresis as a basis for pharmacologic memory and a backbone for once-a-week pan-tuberculosis therapy.Frontiers in pharmacology · 2022Article
- The Genomic Basis of Rapid Adaptation to Antibiotic Combination Therapy in Pseudomonas aeruginosa.Molecular biology and evolution · 2021Article
- Repurposing Cefazolin-Avibactam for the Treatment of Drug ResistantFrontiers in pharmacology · 2021Article
- Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Levofloxacin Pharmacokinetics/Pharmacodynamics, Dosing, Susceptibility Breakpoints, and Artificial Intelligence in the Treatment of Multidrug-resistant Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- The Sterilizing Effect of Intermittent Tedizolid for Pulmonary Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Gatifloxacin Pharmacokinetics/Pharmacodynamics-based Optimal Dosing for Pulmonary and Meningeal Multidrug-resistant Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Pharmacokinetic/Pharmacodynamic Background and Methods and Scientific Evidence Base for Dosing of Second-line Tuberculosis Drugs.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Drug-Penetration Gradients Associated with Acquired Drug Resistance in Patients with Tuberculosis.American journal of respiratory and critical care medicine · 2018Article
- Article
- Absence of hybridization with the wild-type and mutant rpoB probes in the Genotype MTBDRplus assay detects 'disputed' rifampicin mutations.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2018Article
- Antibacterial and Sterilizing Effect of Benzylpenicillin in Tuberculosis.Antimicrobial agents and chemotherapy · 2018Article
- Efficient measurement and factorization of high-order drug interactions inScience advances · 2017Article
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5 authors.
Funding
Abstract
In tuberculosis treatment, susceptibility is defined by a critical concentration of 1.0 mg/liter for rifampin and 0.2 or 1.0 mg/liter for low- and high-level isoniazid resistance on the basis of an epidemiologic cutoff method that uses the distribution of the MICs for isolates. However, pharmacokinetics-pharmacodynamics-based clinical trial simulations suggested that the breakpoints should be 0.0625 mg/liter for rifampin and 0.0312 or 0.125 mg/liter for isoniazid. We examined the outcomes of 36 patients with drug-susceptible tuberculosis whose rifampin and isoniazid MICs were determined, whose plasma drug concentrations were also measured, and who were part of a prospective cohort study in Western Cape, South Africa. We performed classification and regression tree analysis to identify clinical and laboratory factors that predicted 2-month sputum conversion rates and long-term clinical outcomes. Poor long-term clinical outcomes were defined as microbiological failure, relapse, or death within a 2-year follow-up period. Peak drug concentrations and areas under the concentration-time curve were most predictive of outcomes and constituted the primary node, similar to our findings on the larger cohort. However, rifampin and isoniazid MICs improved the predictive capacity of the primary decision node by 20 and 17%, respectively, for these 36 patients. The rifampin MIC cutoff above which there was therapy failure was 0.125 mg/liter, while that of isoniazid was 0.0312 mg/liter; these are similar to those derived in clinical trial simulations. The critical concentrations used to define multidrug resistance for clinical decision making should take clinical outcomes into account.
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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.