ArticleThe Journal of infectious diseases2010
Efflux-pump-derived multiple drug resistance to ethambutol monotherapy in Mycobacterium tuberculosis and the pharmacokinetics and pharmacodynamics of ethambutol.
Article in The Journal of infectious diseases, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Updated antimicrobial dosing recommendations for obese patients.Antimicrobial agents and chemotherapy · 2024Pooled it
- Ethambutol pharmacokinetic variability is linked to body mass in overweight, obese, and extremely obese people.Antimicrobial agents and chemotherapy · 2012Trial
- Falling short: Inadequate target attainment in guideline-based therapy of nontuberculous mycobacterial disease.medRxiv : the preprint server for health sciences · 2026Article
- Designing Antibiotics with Inherent Resistance to Efflux as a Strategy to Revive Discovery against Multidrug-Resistant Pathogens.Journal of medicinal chemistry · 2026Article
- Article
- Preclinical pharmacokinetics/pharmacodynamics studies defining the role of ethambutol inAntimicrobial agents and chemotherapy · 2026Article
- Genomic characterization of multidrug-resistant tuberculosis in Shanghai, China: antibiotic resistance, virulence and transmission.JAC-antimicrobial resistance · 2025Article
- Fluoroquinolones and rifampin combination in the backdrop of heteroresistant tuberculosis.Antimicrobial agents and chemotherapy · 2025Article
- Therapeutic drug monitoring in tuberculosis.European journal of clinical pharmacology · 2024Review
- Role of therapeutic drug monitoring in the treatment of multi-drug resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2024Article
- Omadacycline pharmacokinetics/pharmacodynamics and efficacy against multidrug-resistantAntimicrobial agents and chemotherapy · 2024Article
- TheMicrobiology spectrum · 2024Article
- Impacts of MDR/XDR-TB on the global tuberculosis epidemic: Challenges and opportunities.Current research in microbial sciences · 2024Review
- Meropenem-vaborbactam restoration of first-line drug efficacy and comparison of meropenem-vaborbactam-moxifloxacin versus BPaL MDR-TB regimen.International journal of antimicrobial agents · 2023Article
- Nouveau short-course therapy and morphism mapping for clinical pulmonaryAntimicrobial agents and chemotherapy · 2023Article
- Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023Review
- Isoniazid pharmacokinetics/pharmacodynamics as monotherapy and in combination regimen in the hollow fiber system model of Mycobacterium kansasii.Tuberculosis (Edinburgh, Scotland) · 2023Article
- High Intrapulmonary Rifampicin and Isoniazid Concentrations Are Associated With Rapid Sputum Bacillary Clearance in Patients With Pulmonary Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Diagnostic Accuracy of Therapeutic Drug Monitoring During Tuberculosis Treatment.Journal of clinical pharmacology · 2022Article
- Establishment and evaluation of an overlap extension polymerase chain reaction technique for rapid and efficient detection of drug-resistance in Mycobacterium tuberculosis.Infectious diseases of poverty · 2022Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundEthambutol is used for the treatment of tuberculosis in cases where there is isoniazid resistance. We examined the emergence of drug resistance to ethambutol monotherapy in pharmacokinetic-pharmacodynamic studies of a hollow-fiber system.
methodsDose-effect and dose-scheduling studies were performed with ethambutol and log-phase growth Mycobacterium tuberculosis to identify exposures and schedules linked to optimal kill and resistance suppression. In one study, after 7 days of daily ethambutol, 300 mg isoniazid per day was administered to each system to determine its early bactericidal activity.
resultsEfflux-pump blockage reduced the mutation frequency to ethambutol 64-fold. In dose-effect studies, ethambutol had a maximal early bactericidal activity of 0.22 log10 colony-forming units/mL/day, as is encountered in patients. By day 7, resistance to both ethambutol and isoniazid had increased. Previous exposure to ethambutol halted isoniazid early bactericidal activity. Daily therapy, as opposed to more intermittent therapy, was associated with the least proportion of efflux-pump-driven resistance, consistent with a time-driven effect. Microbial kill was best explained by the ratio of area under the concentration-time curve to minimum inhibitory concentration (r2 = 0.90).
conclusionThe induction of an efflux pump that reduces the effect of multiple drugs provides an alternative pathway to sequential acquisition of mutations in the development of multiple drug resistance.
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