ArticleAntimicrobial agents and chemotherapy2010
New susceptibility breakpoints for first-line antituberculosis drugs based on antimicrobial pharmacokinetic/pharmacodynamic science and population pharmacokinetic variability.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 4 of them syntheses that pooled it.
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Who cites it
78 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- MIC-based tuberculosis drug susceptibility testing using Sensititre MYCOTB: a diagnostic accuracy meta-analysis.Journal of clinical microbiology · 2026Pooled it
- Mathematical models of drug-resistant tuberculosis lack bacterial heterogeneity: A systematic review.PLoS pathogens · 2024Pooled it
- Non-commercial phenotypic assays for the detection of Mycobacterium tuberculosis drug resistance: a systematic review.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2020Pooled 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
- Optimal Sampling Strategies for Therapeutic Drug Monitoring of First-Line Tuberculosis Drugs in Patients with Tuberculosis.Clinical pharmacokinetics · 2019Trial
- Impact of nonlinear interactions of pharmacokinetics and MICs on sputum bacillary kill rates as a marker of sterilizing effect in tuberculosis.Antimicrobial agents and chemotherapy · 2015Trial
- The pyrazinamide susceptibility breakpoint above which combination therapy fails.The Journal of antimicrobial chemotherapy · 2014Trial
- Non-tuberculous mycobacteria in cattle: Distribution, antimicrobial resistance and zoonotic implications in Tamil Nadu, India.Veterinary research communications · 2026Article
- Wild-type MIC distribution and evaluation of epidemiological cut-offs of second-line TB-drugs in susceptible and MDR-TB clinical isolates from Chennai, India.Frontiers in microbiology · 2026Article
- 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
- Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB.IJTLD open · 2024Article
- Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: implications for a diagnostic accuracy.Microbiology spectrum · 2024Article
- Rapid Diagnosis of Drug-Resistant Tuberculosis-Opportunities and Challenges.Pathogens (Basel, Switzerland) · 2023Review
- Phenotypic drug susceptibility characterization and clinical outcomes of tuberculosis strains with A-probe mutation by GeneXpert MTB/RIF.BMC infectious diseases · 2023Article
- Determining the Delamanid Pharmacokinetics/Pharmacodynamics Susceptibility Breakpoint Using Monte Carlo Experiments.Antimicrobial agents and chemotherapy · 2023Article
- Dried Blood Spot Sampling to Assess Rifampicin Exposure and Treatment Outcomes among Native and Non-Native Tuberculosis Patients in Paraguay: An Exploratory Study.Pharmaceutics · 2023Article
- Diagnostic Accuracy of Therapeutic Drug Monitoring During Tuberculosis Treatment.Journal of clinical pharmacology · 2022Article
- Development of 6-Methanesulfonyl-8-nitrobenzothiazinone Based Antitubercular Agents.ACS medicinal chemistry letters · 2022Article
- Population Pharmacokinetics and Pharmacodynamics of Isoniazid and its Metabolite Acetylisoniazid in Chinese Population.Frontiers in pharmacology · 2022Article
18 more citing papers are in PubMed but not listed here.
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Abstract
Arguably, one of the most common and consequential laboratory tests performed in the world is Mycobacterium tuberculosis susceptibility testing. M. tuberculosis resistance is defined by growth of > or =1% of a bacillary inoculum on the critical concentration of an antibiotic. The critical concentration was chosen based on inhibition of > or =95% of wild-type isolates. The critical concentration of isoniazid is either 0.2 or 1.0 mg/liter, that of rifampin is 1.0 mg/liter, that of pyrazinamide is 100 mg/liter, that of ethambutol is 5.0 mg/liter, and that of fluoroquinolones is 1.0 mg/liter. However, the relevance of these concentrations to microbiologic and clinical outcomes is unclear. Critical concentrations were identified using the ability to achieve the antibiotic area under the concentration-time curve/MIC ratio associated with > or =90% of maximal kill (EC(90)) of M. tuberculosis in > or =90% of patients. Population pharmacokinetic parameters and their variability encountered in tuberculosis patients were utilized in Monte Carlo simulations to determine the probability that particular daily doses of the drugs would achieve or exceed the EC(90) in the epithelial lining fluid of 10,000 tuberculosis patients. Failure to achieve EC(90) in > or =90% of patients at a particular MIC was defined as drug resistance. The critical concentrations of moxifloxacin and ethambutol remained unchanged, but a critical concentration of 50 mg/liter was identified for pyrazinamide, 0.0312 mg/liter and 0.125 mg/liter were defined for low- and high-level isoniazid resistance, respectively, and 0.0625 mg/liter was defined for rifampin. Thus, current critical concentrations of first-line antituberculosis drugs are overoptimistic and should be set lower. With the proposed breakpoints, the rates of multidrug-resistant tuberculosis could become 4-fold higher than currently assumed.
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