ArticleAmerican journal of respiratory and critical care medicine2018
Drug-Penetration Gradients Associated with Acquired Drug Resistance in Patients with Tuberculosis.
Article in American journal of respiratory and critical care medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.
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Who cites it
101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- Systematic and quantitative analyses of hollow fiber model ofMicrobiology spectrum · 2026Pooled it
- d-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Pooled it
- MakingCell insight · 2026Review
- Novel regimens for treatment ofbioRxiv : the preprint server for biology · 2026Article
- The Emerging Role of Immunothrombosis in the Control and Pathogenesis of Mycobacterium tuberculosis.The Journal of infectious diseases · 2026Review
- Acquisition of bedaquiline and clofazimine resistance in association with a novel loss-of-function mutation in theASM case reports · 2026Article
- Preclinical pharmacokinetics/pharmacodynamics studies defining the role of ethambutol inAntimicrobial agents and chemotherapy · 2026Article
- Preclinical evaluation of epetraborole in the hollow fibre system model of Mycobacterium abscessus lung disease.The Journal of antimicrobial chemotherapy · 2026Article
- Lipid profiling in nontuberculous mycobacterial pulmonary disease based on geospatial locations and disease severity.ERJ open research · 2026Article
- Pharmacodynamic evidence for tedizolid use inIJTLD open · 2026Article
- Clinical standards for antimicrobial stewardship in TB care.IJTLD open · 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
- The Kinetics of Bedaquiline Diffusion in Tuberculous Cavities Open a Window for the Emergence of Resistance.The Journal of infectious diseases · 2025Article
- Tigecycline pharmacodynamics in the hollow fiber system ofbioRxiv : the preprint server for biology · 2025Article
- Fluoroquinolones and rifampin combination in the backdrop of heteroresistant tuberculosis.Antimicrobial agents and chemotherapy · 2025Article
- Assessing Infectiousness and the Impact of Effective Treatment to Guide Isolation Recommendations for People With Pulmonary Tuberculosis.The Journal of infectious diseases · 2025Review
- Tigecycline pharmacodynamics in the hollow fiber system ofFrontiers in pharmacology · 2025Article
- Methods and Models for StudyingInternational journal of molecular sciences · 2024Review
- Toward better cures forClinical microbiology reviews · 2024Review
- Examining effective monotherapy hypothesis for TB therapy failure and resistance emergence.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2024Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleAcquired resistance is an important driver of multidrug-resistant tuberculosis (TB), even with good treatment adherence. However, exactly what initiates the resistance and how it arises remain poorly understood.
objectivesTo identify the relationship between drug concentrations and drug susceptibility readouts (minimum inhibitory concentrations [MICs]) in the TB cavity.
methodsWe recruited patients with medically incurable TB who were undergoing therapeutic lung resection while on treatment with a cocktail of second-line anti-TB drugs. On the day of surgery, antibiotic concentrations were measured in the blood and at seven prespecified biopsy sites within each cavity. Mycobacterium tuberculosis was grown from each biopsy site, MICs of each drug identified, and whole-genome sequencing performed. Spearman correlation coefficients between drug concentration and MIC were calculated. MEASUREMENTS AND MAIN
resultsFourteen patients treated for a median of 13 months (range, 5-31 mo) were recruited. MICs and drug resistance-associated single-nucleotide variants differed between the different geospatial locations within each cavity, and with pretreatment and serial sputum isolates, consistent with ongoing acquisition of resistance. However, pretreatment sputum MIC had an accuracy of only 49.48% in predicting cavitary MICs. There were large concentration-distance gradients for each antibiotic. The location-specific concentrations inversely correlated with MICs (P < 0.05) and therefore acquired resistance. Moreover, pharmacokinetic/pharmacodynamic exposures known to amplify drug-resistant subpopulations were encountered in all positions.
conclusionsThese data inform interventional strategies relevant to drug delivery, dosing, and diagnostics to prevent the development of acquired resistance. The role of high intracavitary penetration as a biomarker of antibiotic efficacy, when assessing new regimens, requires clarification.
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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.