Partnerships to Design Novel Regimens to Treat Childhood Tuberculosis, Sui Generis: The Road Ahead
There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development. We propose a program of investigation that would take this forward into a systematic and comprehensive...
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Gumbo, T., Makhene, M. K., Seddon, J. A. Tags: A DEVELOPMENT PARADIGM FOR NOVEL COMBINATION REGIMENS FOR MULTIDRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN CHILDREN: FLAME FOR WORK AND PLAY Source Type: research
Optimal Clinical Doses of Faropenem, Linezolid, and Moxifloxacin in Children With Disseminated Tuberculosis: Goldilocks
Conclusions. The regimen and doses of linezolid, moxifloxacin, and faropenem identified are proposed to be adequate for all disseminated tuberculosis syndromes, whether drug-resistant or -susceptible. (Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Srivastava, S., Deshpande, D., Pasipanodya, J., Nuermberger, E., Swaminathan, S., Gumbo, T. Tags: A DEVELOPMENT PARADIGM FOR NOVEL COMBINATION REGIMENS FOR MULTIDRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN CHILDREN: FLAME FOR WORK AND PLAY Source Type: research
A Faropenem, Linezolid, and Moxifloxacin Regimen for Both Drug-Susceptible and Multidrug-Resistant Tuberculosis in Children: FLAME Path on the Milky Way
Conclusions. We have developed an oral faropenem-linezolid-moxifloxacin (FLAME) regimen that is free of first-line drugs. The regimen could be effective against both multidrug-resistant and drug-susceptible tuberculosis in children. (Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Deshpande, D., Srivastava, S., Nuermberger, E., Pasipanodya, J. G., Swaminathan, S., Gumbo, T. Tags: A DEVELOPMENT PARADIGM FOR NOVEL COMBINATION REGIMENS FOR MULTIDRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN CHILDREN: FLAME FOR WORK AND PLAY Source Type: research
Concentration-Dependent Synergy and Antagonism of Linezolid and Moxifloxacin in the Treatment of Childhood Tuberculosis: The Dynamic Duo
Conclusions. We identified doses and dose schedules of a linezolid and moxifloxacin backbone regimen that could be highly efficacious in disseminated tuberculosis in children. (Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Deshpande, D., Srivastava, S., Nuermberger, E., Pasipanodya, J. G., Swaminathan, S., Gumbo, T. Tags: A DEVELOPMENT PARADIGM FOR NOVEL COMBINATION REGIMENS FOR MULTIDRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN CHILDREN: FLAME FOR WORK AND PLAY Source Type: research
Linezolid for Infants and Toddlers With Disseminated Tuberculosis: First Steps
Conclusions. We identified the linezolid AUC0–24/MIC target for optimal efficacy against pediatric intracellular tuberculosis, and an AUC0–24 threshold associated with mitochondrial inhibition. These constitute a therapeutic window to be targeted for optimal linezolid doses in children with tuberculosis. (Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Deshpande, D., Srivastava, S., Pasipanodya, J. G., Bush, S. J., Nuermberger, E., Swaminathan, S., Gumbo, T. Tags: A DEVELOPMENT PARADIGM FOR NOVEL COMBINATION REGIMENS FOR MULTIDRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN CHILDREN: FLAME FOR WORK AND PLAY Source Type: research
A Combination Regimen Design Program Based on Pharmacodynamic Target Setting for Childhood Tuberculosis: Design Rules for the Playground
Children with tuberculosis are treated with drug regimens copied from adults despite significant differences in antibiotic pharmacokinetics, pathology, and the microbial burden between childhood and adult tuberculosis. We sought to develop a new and effective oral treatment regimen specific to children of different ages. We investigated and validated the concept that target drug concentrations associated with therapy failure and death in children are different from those of adults. On that basis, we proposed a 4-step program to rapidly develop treatment regimens for children. First, target drug concentrations for optimal e...
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Srivastava, S., Deshpande, D., Pasipanodya, J. G., Thomas, T., Swaminathan, S., Nuermberger, E., Gumbo, T. Tags: A DEVELOPMENT PARADIGM FOR NOVEL COMBINATION REGIMENS FOR MULTIDRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN CHILDREN: FLAME FOR WORK AND PLAY Source Type: research
Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests
Conclusions. We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis. (Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Swaminathan, S., Pasipanodya, J. G., Ramachandran, G., Hemanth Kumar, A. K., Srivastava, S., Deshpande, D., Nuermberger, E., Gumbo, T. Tags: A DEVELOPMENT PARADIGM FOR NOVEL COMBINATION REGIMENS FOR MULTIDRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN CHILDREN: FLAME FOR WORK AND PLAY Source Type: research
Harnessing Novel Quantitative Pharmacology Approaches to Optimize the Treatment of Children With Tuberculosis
(Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Seddon, J. A., Makhene, M. K. Tags: A DEVELOPMENT PARADIGM FOR NOVEL COMBINATION REGIMENS FOR MULTIDRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN CHILDREN: FLAME FOR WORK AND PLAY Source Type: research
Transmission of HCV NS5A Inhibitor-Resistant Variants Among HIV-Infected Men Who Have Sex With Men
(Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Abravanel, F., Metivier, S., Chauveau, M., Peron, J.-M., Izopet, J. Tags: CORRESPONDENCE Source Type: research
Reply to Petti
(Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Kanamori, H., Weber, D. J., Rutala, W. A. Tags: CORRESPONDENCE Source Type: research
Healthcare Outbreaks Associated With Dental Unit Water Systems: Strong Scientific Evidence of Minimal Risk
(Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Petti, S. Tags: CORRESPONDENCE Source Type: research
Invasive Group A Streptococcal Infections in Indigenous New Zealanders With Type 2 Diabetes
(Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Williamson, D. A., Moreland, N. J., Jack, S. Tags: CORRESPONDENCE Source Type: research
Reply to Skowronski et al
(Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: DiazGranados, C. A., Dunning, A. J., Robertson, C. A., Talbot, H. K., Landolfi, V., Greenberg, D. P. Tags: CORRESPONDENCE Source Type: research
More Furious Than Ever: Escherichia coli-Acquired Co-resistance Toward Colistin and Carbapenems
(Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Kumar, M., Saha, S., Subudhi, E. Tags: CORRESPONDENCE Source Type: research
Repeat Influenza Vaccination and High-Dose Efficacy
(Source: Clinical Infectious Diseases)
Source: Clinical Infectious Diseases - October 13, 2016 Category: Infectious Diseases Authors: Skowronski, D. M., Chambers, C., Gilca, R., De Serres, G. Tags: CORRESPONDENCE Source Type: research
