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

Maleck V. Vasseur (1) , Marlène Z. Lacroix (1) , Pierre-Louis Toutain (1) , Alain Bousquet‐mélou (1) , Aude A. Ferran (1)

1 ToxAlim - ToxAlim

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.

Domaines: Sciences du Vivant [q-bio]

Maleck V. Vasseur, Marlène Z. Lacroix, Pierre-Louis Toutain, Alain Bousquet‐mélou, Aude A. Ferran. Infection-stage adjusted dose of beta-lactams for parsimonious and efficient antibiotic treatments: A Pasteurella multocida experimental pneumonia in mice. PLoS ONE, 2017, 12 (8), 14 p. ⟨10.1371/journal.pone.0182863⟩. ⟨hal-01604263⟩