The early bactericidal activity of antituberculosis drugs

Diacon, Andreas H.; Donald, Peter R.

doi:10.1586/14787210.2014.870884

Cited by 42 publications

(39 citation statements)

References 61 publications

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“…In contrast to dose-fractionation studies, EBA studies do not break the collinearity of PK/PD parameters. [10,13] For most anti-TB drugs, the AUC 0-24 h relative to the MIC has been suggested as the best parameter to predict in vivo efficacy of drugs against Mtb. [9][10][11]14] As only unbound drug is active, the free AUC is often used as a target.…”

Section: Pk/pdmentioning

confidence: 99%

“…This study shows that when a mean MIC of TB isolates is known, the EBA that is found in human EBA studies is mediated through an AUC 0-24 h /MIC ratio that is achieved in an in vitro TB model. [13,17] The AUC 0-24 h was also linked to treatment outcome in the study of Pasipanodya et al (2013). They showed that the AUC of pyrazinamide, rifampicin, and isoniazid below a certain threshold, were predictors of a poor long-term outcome.…”

Section: Efficacymentioning

confidence: 99%

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Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

Zuur

Bolhuis

Anthony

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in tuberculosis treatment. Areas covered: Literature on pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs was explored to evaluate the effect of drug exposure in relation to drug susceptibility, toxicity and efficacy. New, down-sized strategies, like dried blood spot analysis and limited sampling strategies are reviewed. In addition, molecular resistance testing of Mycobacteria tuberculosis, combining a short turn-around time with relevant information on drug susceptibility of the causative pathogen was explored. Newly emerging host biomarkers provide information on the response to treatment. Expert opinion: Therapeutic drug monitoring can minimize toxicity and increase efficacy of tuberculosis treatment and prevent the development of resistance. Dried blood spot analysis and limited sampling strategies, can be combined to provide us with a more patient friendly approach. Furthermore, rapid information on drug susceptibility by molecular testing, and information from host biomarkers on the bacteriological response, can be used to further optimize tuberculosis treatment. ARTICLE HISTORY

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Section: Pk/pdmentioning

confidence: 99%

Section: Efficacymentioning

confidence: 99%

Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

Zuur

Bolhuis

Anthony

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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“…The therapist uses the mycobacterial count in sputum to follow the impact of combination therapy and to adjust its length. Clinical trialists subject sputum to the early bactericidal activity test as a gateway through which any new TB drug candidate must pass if it is to go on to larger, longer, and far more expensive tests of efficacy in combination with other drugs (4).…”

Section: New Evidence For the Complexity Of The Population Structure mentioning

confidence: 99%

New Evidence for the Complexity of the Population Structure of Mycobacterium tuberculosis Increases the Diagnostic and Biologic Challenges

Dartois

Saito

Warrier

et al. 2016

Am J Respir Crit Care Med

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developing serotype-independent vaccines on the basis of these targets are not promising.Major limitations of the study-which are probably unresolvable because of the human model-are that the results addressed only one pneumococcal serotype and that only easily accessible circulating B cells were measured, whereas typical B-cell reservoirs like spleen, lymph nodes, and bone marrow were omitted. Particularly, the longlived population of plasma cells residing in the bone marrow could not be assessed, and we still do not know their role in mucosal protection against pneumococci in men (14). Other limitations, such as using only simple methods like enzyme-linked immunospot assay to discriminate plasma cells from the memory B cells instead of flow cytometry, can and should be addressed in future studies.In conclusion, this study identified polysaccharide memory B cells as an immunological correlate for mucosal protection, which, if confirmed, could become an immunological outcome parameter in studies investigating pneumococcal vaccines. n

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“…This method provides reproducible results regarding efficacy although it does not reliably predict sterilising activity. The technique is mainly used for dose finding and preliminary evaluation of toxicity in a small sample [102] up to 14 days. Using this approach to evaluate PA-824, it has been shown that the mean multi-agent 14-day EBA of PA-824, moxifloxacin and pyrazinamide is comparable with that of the current standard treatment and significantly higher than those of bedaquiline, bedaquiline with pyrazinamide, and bedaquiline with PA-824 [47].…”

Section: Novel Designs For Clinical Trialsmentioning

confidence: 99%

Novel drugs against tuberculosis: a clinician's perspective

et al. 2014

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The United Nations Millennium Development Goal of reversing the global spread of tuberculosis by 2015 has been offset by the rampant re-emergence of drug-resistant tuberculosis, in particular fluoroquinolone-resistant multidrug-resistant and extensively drug-resistant tuberculosis. After decades of quiescence in the development of antituberculosis medications, bedaquiline and delamanid have been conditionally approved for the treatment of drug-resistant tuberculosis, while several other novel compounds (AZD5847, PA-824, SQ109 and sutezolid) have been evaluated in phase II clinical trials. Before novel drugs can find their place in the battle against drug-resistant tuberculosis, linezolid has been compassionately used with success in the treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis. This review largely discusses six novel drugs that have been evaluated in phase II and III clinical trials, with focus on the clinical evidence for efficacy and safety, potential drug interactions, and prospect for using multiple novel drugs in new regimens. @ERSpublications A review of the efficacy, safety, and potential of new drugs to improve TB therapy from the perspective of clinicians

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The early bactericidal activity of antituberculosis drugs

Cited by 42 publications

References 61 publications

Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

New Evidence for the Complexity of the Population Structure of Mycobacterium tuberculosis Increases the Diagnostic and Biologic Challenges

Novel drugs against tuberculosis: a clinician's perspective

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