Combinations of β-Lactam Antibiotics Currently in Clinical Trials Are Efficacious in a DHP-I-Deficient Mouse Model of Tuberculosis Infection.
- Rullas J Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡
- Dhar N School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡
- McKinney JD School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡
- García-Pérez A Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡
- Lelievre J Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡
- Diacon AH Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡ Department of Medical Biochemistry, Stellenbosch University, Tygerberg, South Africa.
- Hugonnet JE Centre de Recherche des Cordeliers, LRMA, Equipe 12, Université Pierre et Marie Curie-Paris 6, UMR S 872, Paris, France Institut National de la Santé et de la Recherche Médicale (INSERM), U872, Paris, France Université Paris Descartes, Sorbonne Paris Cité, UMR S 872, Paris, France Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡
- Arthur M Centre de Recherche des Cordeliers, LRMA, Equipe 12, Université Pierre et Marie Curie-Paris 6, UMR S 872, Paris, France Institut National de la Santé et de la Recherche Médicale (INSERM), U872, Paris, France Université Paris Descartes, Sorbonne Paris Cité, UMR S 872, Paris, France Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡
- Angulo-Barturen I Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡
- Barros-Aguirre D Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡
- Ballell L Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain Open Collaborative Model for Tuberculosis Lead Optimisation (ORCHID) Consortium‡ lluis.p.ballell@gsk.com.
- 2015-05-20
Published in:
- Antimicrobial agents and chemotherapy. - 2015
Animals
Anti-Bacterial Agents
Dipeptidases
Disease Models, Animal
Drug Therapy, Combination
GPI-Linked Proteins
Lung
Mice
Mice, Inbred C57BL
Microbial Sensitivity Tests
Mycobacterium tuberculosis
Respiratory Tract Infections
Staphylococcal Infections
Tuberculosis
beta-Lactams
English
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.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1128/AAC.01063-15
- PMID 25987618
- Persistent URL
- https://sonar.ch/global/documents/176962
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