5 years ago

Infection-stage adjusted dose of beta-lactams for parsimonious and efficient antibiotic treatments: A <i>Pasteurella multocida</i> experimental pneumonia in mice

Marlene Z. Lacroix, Maleck V. Vasseur, Aude A. Ferran, Pierre-Louis Toutain, Alain Bousquet-Melou

by Maleck V. Vasseur, Marlene Z. Lacroix, Pierre-Louis Toutain, Alain Bousquet-Melou, Aude A. Ferran

In this study, the impact of infection stage on clinically and microbiologically efficacious doses and on antibiotic consumption was assessed during a naturally evolving infectious disease, using an original mouse model of pulmonary infection produced by air-borne contamination. When Pasteurella multocida was administered as pathogenic agent to immunocompetent mice, 60% of the animals exhibited clinical symptoms of pneumonia 2 to 4 days after bacterial contamination of the lungs. Two beta-lactam antibiotics were evaluated: amoxicillin and cefquinome, a fourth generation cephalosporin developed for food animals. First, a pharmacokinetic study was performed in infected mice to determine the exposure to amoxicillin or cefquinome required to treat clinically affected animals, based on the targeted values of PK/PD indices for beta-lactams. We then confirmed that these doses resulted in a 100% clinical cure rate in animals exhibiting clinical signs of infection and harboring a high pathogenic inoculum. More interestingly, we also showed that the same 100% clinical cure could be obtained in our model with 10-fold lower doses in animals at pre-patent stages of infection i.e. when harboring a low pathogenic inoculum. At the group level, antimicrobial drug consumption was reduced by treating animals at an early stage of the infection course with a pre-patent tailored dose. These results suggest that early treatment with a dose suitably adjusted to the stage of infection might help to reduce both overall antibiotic consumption and resistance selection pressure in the animals and in the environment.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.pone.0182863

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