Infoscience

Journal article

Combinations of beta-Lactam Antibiotics Currently in Clinical Trials Are Efficacious in a DHP-I-Deficient Mouse Model of Tuberculosis Infection

Rullas, Joaquin; Dhar, Neeraj; Mckinney, John D.; Garcia-Perez, Adolfo; Lelievre, Joel; Diacon, Andreas H.; Hugonnet, Jean-Emmanuel; Arthur, Michel; Angulo-Barturen, Inigo; Barros-Aguirre, David
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  • Published in: Antimicrobial Agents And Chemotherapy (ISSN: 0066-4804), vol. 59, num. 8, p. 4997-4999
  • Washington: American Society for Microbiology, 2015

We report here a dehydropeptidase-deficient murine model of tuberculosis (TB) infection that is able to partially uncover the efficacy of marketed broad-spectrum beta-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 beta-lactams as safe and mycobactericidal components of new combination regimens against TB with or without resistance to currently used drugs.

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