Treatment with Atorvastatin Provides Additional Benefits to Imipenem in a Model of Gram-Negative Pneumonia Induced by Klebsiella pneumoniae in Mice.
Antimicrob Agents Chemother
; 62(5)2018 05.
Article
em En
| MEDLINE
| ID: mdl-29463546
ABSTRACT
The clinical pathogen Klebsiella pneumoniae is a relevant cause of nosocomial infections, and resistance to current treatment with carbapenem antibiotics is becoming a significant problem. Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) used for controlling plasma cholesterol levels. There is clinical evidence showing other effects of statins, including decrease of lung inflammation. In the current study, we show that pretreatment with atorvastatin markedly attenuated lung injury, which was correlated with a reduction in the cellular influx into the alveolar space and lungs and downmodulation of the production of proinflammatory mediators in the initial phase of infection in C57BL/6 mice with K. pneumoniae However, atorvastatin did not alter the number of bacteria in the lungs and blood of infected mice, despite decreasing local inflammatory response. Interestingly, mice that received combined treatment with atorvastatin and imipenem displayed better survival than mice treated with vehicle, atorvastatin, or imipenem alone. These findings suggest that atorvastatin could be an adjuvant in host-directed therapies for multidrug-resistant K. pneumoniae, based on its powerful pleiotropic immunomodulatory effects. Together with antimicrobial approaches, combination therapy with anti-inflammatory compounds could improve the efficiency of therapy during acute lung infections.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por Klebsiella
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Imipenem
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Pneumonia Bacteriana
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Inibidores de Hidroximetilglutaril-CoA Redutases
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Atorvastatina
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Klebsiella pneumoniae
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Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article