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pyrazinamide

  • Open Access
    How To Optimally Combine Genotypic and Phenotypic Drug Susceptibility Testing Methods for Pyrazinamide
    Mechanisms of Resistance
    How To Optimally Combine Genotypic and Phenotypic Drug Susceptibility Testing Methods for Pyrazinamide

    False-susceptible phenotypic drug-susceptibility testing (DST) results for pyrazinamide due to mutations with MICs close to the critical concentration (CC) confound the classification of pncA resistance mutations, leading to an underestimate of the specificity of genotypic DST. This could be minimized by basing treatment decisions on well-understood mutations and by adopting an area of technical uncertainty for phenotypic DST...

    Claudio U. Köser, Daniela M. Cirillo, Paolo Miotto
  • Open Access
    Mechanistic Modeling of <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Infection in Murine Models for Drug and Vaccine Efficacy Studies
    Editor's Pick Experimental Therapeutics
    Mechanistic Modeling of Mycobacterium tuberculosis Infection in Murine Models for Drug and Vaccine Efficacy Studies

    Tuberculosis (TB) drug, regimen, and vaccine development rely heavily on preclinical animal experiments, and quantification of bacterial and immune response dynamics is essential for understanding drug and vaccine efficacy. A mechanism-based model was built to describe Mycobacterium tuberculosis H37Rv infection over time in BALB/c and athymic nude mice, which...

    Nan Zhang, Natasha Strydom, Sandeep Tyagi, Heena Soni, Rokeya Tasneen, Eric L. Nuermberger, Rada M. Savic
  • Open Access
    Regrowth of <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Populations Exposed to Antibiotic Combinations Is Due to the Presence of Isoniazid and Not Bacterial Growth Rate
    Susceptibility
    Regrowth of Mycobacterium tuberculosis Populations Exposed to Antibiotic Combinations Is Due to the Presence of Isoniazid and Not Bacterial Growth Rate

    Modulation of the growth rate in Mycobacterium tuberculosis is key to its survival in the host, particularly with regard to its adaptation during chronic infection, when the growth rate is very slow. The resulting physiological changes influence the way in which this pathogen interacts with the host and responds to antibiotics. Therefore, it is important that we...

    Charlotte L. Hendon-Dunn, Henry Pertinez, Alice A. N. Marriott, Kim A. Hatch, Jon C. Allnutt, Geraint Davies, Joanna Bacon
  • Introducing RpsA Point Mutations Δ438A and D123A into the Chromosome of <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Confirms Their Role in Causing Resistance to Pyrazinamide
    Mechanisms of Resistance
    Introducing RpsA Point Mutations Δ438A and D123A into the Chromosome of Mycobacterium tuberculosis Confirms Their Role in Causing Resistance to Pyrazinamide

    Pyrazinamide (PZA) is a unique frontline drug for shortening tuberculosis (TB) treatment, but its mechanisms of action are elusive. We previously found one PZA-resistant strain that harbors an alanine deletion at position 438 (Δ438A) in RpsA, a target of PZA associated with PZA resistance, but its role in causing PZA resistance has been inconclusive.

    Wanliang Shi, Peng Cui, Hongxia Niu, Shuo Zhang, Tone Tønjum, Bingdong Zhu, Ying Zhang
  • Open Access
    Contribution of Pretomanid to Novel Regimens Containing Bedaquiline with either Linezolid or Moxifloxacin and Pyrazinamide in Murine Models of Tuberculosis
    Experimental Therapeutics
    Contribution of Pretomanid to Novel Regimens Containing Bedaquiline with either Linezolid or Moxifloxacin and Pyrazinamide in Murine Models of Tuberculosis

    Novel regimens combining bedaquiline and pretomanid with either linezolid (BPaL regimen) or moxifloxacin and pyrazinamide (BPaMZ regimen) shorten the treatment duration needed to cure tuberculosis (TB) in BALB/c mice compared to that of the first-line regimen and have yielded promising results in initial clinical trials. However, the independent contribution of the investigational new drug pretomanid to the efficacy of BPaMZ has not...

    Jian Xu, Si-Yang Li, Deepak V. Almeida, Rokeya Tasneen, Kala Barnes-Boyle, Paul J. Converse, Anna M. Upton, Khisimuzi Mdluli, Nader Fotouhi, Eric L. Nuermberger
  • Open Access
    A Diagnostic Algorithm To Investigate Pyrazinamide and Ethambutol Resistance in Rifampin-Resistant <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Isolates in a Low-Incidence Setting
    Susceptibility
    A Diagnostic Algorithm To Investigate Pyrazinamide and Ethambutol Resistance in Rifampin-Resistant Mycobacterium tuberculosis Isolates in a Low-Incidence Setting

    Phenotypic drug susceptibility testing (DST) for the two first-line tuberculosis drugs ethambutol and pyrazinamide is known to yield unreliable and inaccurate results. In this prospective study, we propose a diagnostic algorithm combining phenotypic DST with Sanger sequencing to inform clinical decision-making for drug-resistant Mycobacterium tuberculosis complex...

    Söenke Andres, Matthias I. Gröschel, Doris Hillemann, Matthias Merker, Stefan Niemann, Katharina Kranzer
  • Role of Therapeutic Drug Monitoring in Treatment Optimization in Tuberculosis and Diabetes Mellitus Comorbidity
    Letter to the Editor
    Role of Therapeutic Drug Monitoring in Treatment Optimization in Tuberculosis and Diabetes Mellitus Comorbidity
    B. G. J. Dekkers, O. W. Akkerman, J. W. C. Alffenaar
  • Letter to the Editor
    Whole-Genome Sequencing To Guide the Selection of Treatment for Drug-Resistant Tuberculosis
    Navisha Dookie, Kogieleum Naidoo, Nesri Padayatchi
  • Mechanisms of Resistance
    Identification of Novel Mutations in LprG (rv1411c), rv0521, rv3630, rv0010c, ppsC, and cyp128 Associated with Pyrazinoic Acid/Pyrazinamide Resistance in Mycobacterium tuberculosis
    Wanliang Shi, Jiazhen Chen, Shuo Zhang, Wenhong Zhang, Ying Zhang
  • Clinical Therapeutics
    Protein Binding of First-Line Antituberculosis Drugs
    Wael A. Alghamdi, Mohammad H. Al-Shaer, Charles A. Peloquin

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