|1758-2||ATORVASTATIN AS AN ADJUVANT TO CARBAPENIC ANTIBIOTIC THERAPY IN A MICE MODEL OF PNEUMONIA|
|Autores:||Talles Prosperi de Paula (UFMG - Universidade Federal de Minas Gerais) ; Raquel Duque do Nascimento Arifa (UFMG - Universidade Federal de Minas Gerais) ; Caio Tavares Fagundes (UFMG - Universidade Federal de Minas Gerais) ; Zélia Menezes Garcia (UFMG - Universidade Federal de Minas Gerais) ; Renata Lacerda de Lima (UFMG - Universidade Federal de Minas Gerais) ; Mauro Martins Teixeira (UFMG - Universidade Federal de Minas Gerais) ; Danielle da Glória de Souza (UFMG - Universidade Federal de Minas Gerais) |
Introduction: Klebsiella pneumoniae is a clinical relevant gram negative bacterium present in nosocomial infections involved with resistance to antibiotic treatment. Statins are inhibitors of coenzyme HMG-CoA that are well known to control cholesterol levels and cardiovascular diseases. Some clinical evidences describe pleiotropic effects of some statins including an increase in survival of patients after pulmonary pneumonia. We hypothesized that atorvastatin could be a possible adjuvant to imipenem treatment through the decrease of inflammatory responses in a model of mice pneumonia.
Methods: This project was approved by CETEA/UFMG. Female C57/BL6 (8-12 weeks) were pre-treated with 10mg/kg of atorvastatin or vehicle 24h before infection with Klebsiella pneumoniae ATCC-27736. After anesthesia with xylazine/ketamine 30 µL of a suspension containing 3 X 106 CFU/mL of K. pneumoniae or saline was administered intranasally. During the lethality experiments animals were treated daily until the end of the analyses. Imipenem was given by intravenously suspension every 12 hours for 5 days. Some animals were submitted to survival experiments others were sacrificed 24h after infection. Lungs were collected to analyse MPO levels, cytokines and chemokine levels, histopathological analysis and bacterial loads. BAL was performed to reach polimorfonuclear infiltration.
Results and discussion. Infected mice treated with vehicles presented an increase in inflammatory responses. Previous and post treatment with atorvastatin decreases the cell influx of neutrophils in the broncoalveolar fluid during pulmonary infection. Treatment with imipenem decreased significantly the loads of bacterium in the lungs of infected mice after 12h of treatment. Mice post-treated with the combination imipenem and atorvastatin had a significant decrease of inflammatory responses and survival than mice treated with vehicle, atorvastatin or imipenem alone.
Conclusions: Here we hypothesized that atorvastatin could be a possible adjuvant to carbapenic antibiotic imipenem treatment decreasing inflammatory responses and increasing survival in mice model of pneumonia.
Finantial support: CAPES, CNPq and FAPEMIG.
Palavras-chave: Klebsella pneumoniae, atorvastatin, imipenem, inflammation, pulmonary pneumonia