Abstract
We report here a dehydropeptidase-deficient murine model of tuberculosis (TB) infection that is able to partially uncover the efficacy of marketed broad-spectrum β-lactam antibiotics alone and in combination. Reductions of up to 2 log CFU in the lungs of TB-infected mice after 8 days of treatment compared to untreated controls were obtained at blood drug concentrations and time above the MIC (T>MIC) below clinically achievable levels in humans. These findings provide evidence supporting the potential of β-lactams as safe and mycobactericidal components of new combination regimens against TB with or without resistance to currently used drugs.
Copyright © 2015, Rullas et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / pharmacology*
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Dipeptidases / deficiency*
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Disease Models, Animal
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Drug Therapy, Combination / methods
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GPI-Linked Proteins / deficiency
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Lung / metabolism
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Lung / microbiology
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Mice
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Mice, Inbred C57BL
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Microbial Sensitivity Tests / methods
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Mycobacterium tuberculosis / drug effects
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Respiratory Tract Infections / drug therapy*
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Respiratory Tract Infections / metabolism
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Respiratory Tract Infections / microbiology
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Staphylococcal Infections / drug therapy
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Staphylococcal Infections / metabolism
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Staphylococcal Infections / microbiology
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Tuberculosis / drug therapy*
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Tuberculosis / metabolism
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Tuberculosis / microbiology
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beta-Lactams / pharmacology*
Substances
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Anti-Bacterial Agents
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GPI-Linked Proteins
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beta-Lactams
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Dipeptidases
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dipeptidase 1