Treatment with Atorvastatin Provides Additional Benefits to Imipenem in a Model of Gram-Negative Pneumonia Induced by Klebsiella pneumoniae in Mice

Antimicrobial Agents and Chemotherapy
Talles Prosperi de PaulaDanielle G Souza

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 eff...Continue Reading

References

Jan 1, 1988·Methods in Enzymology·P J Bailey
Sep 7, 1995·The New England Journal of Medicine·J A KobashigawaG A Cogert
Jan 1, 1997·Endothelium : Journal of Endothelial Cell Research·I MoritaS Murota
Aug 17, 1999·European Journal of Pharmacology·I M MatosM M Teixeira
Aug 25, 1999·Lancet·R S RosensonL C Casey
Apr 3, 2002·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·O GripS Lindgren
Apr 12, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Judy M Hickman-DavisSadis Matalon
Jun 14, 2003·The Journal of Antimicrobial Chemotherapy·F C Odds
Jul 16, 2003·Circulation·Mehdi H ShishehborStanley L Hazen
Mar 17, 2004·British Journal of Pharmacology·Mônica A N D FerreiraSilvia P Andrade
Aug 3, 2004·Nature Reviews. Drug Discovery·Ted T Ashburn, Karl B Thor
Dec 14, 2004·American Journal of Respiratory and Critical Care Medicine·Michael B FesslerG Scott Worthen
Jun 23, 2005·European Journal of Pharmacology·Michele M BarsanteMauro M Teixeira
Jul 7, 2005·Circulation·Marc W MerxChristian Weber
Nov 5, 2005·Experimental and Molecular Pathology·Meir DjaldettiHanna Bessler
Dec 13, 2005·Nature Reviews. Drug Discovery·Mukesh K Jain, Paul M Ridker
Jan 13, 2006·PLoS Medicine·Joseph P Mizgerd
Mar 1, 2006·Critical Care Medicine·Massimo ChelloElvio Covino
Aug 1, 2006·Thorax·E HothersallN C Thomson
Aug 23, 2006·Clinical and Experimental Pharmacology & Physiology·Hong-Wei YaoJian-Ping Zhu
Jun 30, 2007·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Chi-Tai FangShan-Chwen Chang
Apr 1, 2008·The American Journal of Medicine·Igor KarpLouise Pilote
Oct 29, 2008·The American Journal of Medicine·James D ChalmersAdam T Hill
Nov 1, 2008·Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America·Gopi PatelDavid P Calfee
Nov 8, 2008·Nature Medicine·Raewyn Broady, Megan K Levings
Mar 28, 2009·The Lancet Infectious Diseases·Patrice NordmannThierry Naas
Jul 18, 2009·American Journal of Respiratory and Critical Care Medicine·Amir A ZekiNicholas J Kenyon
Sep 29, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christopher R CroweJay K Kolls
Oct 14, 2009·Archives of Internal Medicine·Imad M TleyjehTalal Ibrahim
Dec 26, 2009·Biochemical and Biophysical Research Communications·Shohei ShinozakiMasao Kaneki
Jan 23, 2010·The Journal of Clinical Investigation·Jason W RoschElaine I Tuomanen
Jul 10, 2010·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Raul E IsturizJulio Ramirez
Jul 28, 2010·Clinical and Experimental Pharmacology & Physiology·Jin Woo KimYoung Kyoon Kim
Sep 25, 2010·The American Journal of Pathology·Gerritje J W van der WindtTom van der Poll
Oct 13, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shanshan CaiSamithamby Jeyaseelan
Dec 2, 2010·Southern Medical Journal·Ryan S ArnoldDaniel J Morgan
Aug 24, 2011·Antimicrobial Agents and Chemotherapy·Krisztina M Papp-WallaceRobert A Bonomo
Sep 14, 2011·PloS One·Peter BergmanLinda Björkhem-Bergman

❮ Previous
Next ❯

Citations

May 8, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Luciana P TavaresFrancesca Levi-Schaffer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Bacterial Pneumonia (ASM)

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Carbapenems (ASM)

Carbapenems are members of the beta lactam class of antibiotics and are used for the treatment of severe or high-risk bacterial infections. Discover the latest research on carbapenems here.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Bacterial Pneumonia

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Carbapenems

Carbapenems are members of the beta lactam class of antibiotics and are used for the treatment of severe or high-risk bacterial infections. Discover the latest research on carbapenems here.