title: Studies on the antibacterial effects of statins--in vitro and in vivo.
abstract: BACKGROUND
  Statin treatment has been associated with a beneficial outcome on respiratory tract infections. In addition, previous in vitro and in vivo experiments have indicated favorable effects of statins in bacterial infections.
  
  
  OBJECTIVE
  The aim of the present study was to elucidate possible antibacterial effects of statins against primary pathogens of the respiratory tract.
  
  
  METHODS
  MIC-values for simvastatin, fluvastatin and pravastatin against S. pneumoniae, M. catarrhalis and H. influenzae were determined by traditional antibacterial assays. A BioScreen instrument was used to monitor effects of statins on bacterial growth and to assess possible synergistic effects with penicillin. Bacterial growth in whole blood and serum from healthy volunteers before and after a single dose of simvastatin, fluvastatin and penicillin (positive control) was determined using a blood culture system (BactAlert).
  
  
  RESULTS
  The MIC-value for simvastatin against S pneumoniae and M catarrhalis was 15 µg/mL (36 mmol/L). Fluvastatin and Pravastatin showed no antibacterial effect in concentrations up to 100 µg/mL (230 µmol/L). Statins did not affect growth or viability of H influenzae. Single doses of statins given to healthy volunteers did not affect growth of pneumococci, whereas penicillin efficiently killed all bacteria.
  
  
  CONCLUSIONS
  Simvastatin at high concentrations 15 µg/mL (36 µmol/L) rapidly kills S pneumoniae and M catarrhalis. However, these concentrations by far exceed the concentrations detected in human blood during simvastatin therapy (1-15 nmol/L) and single doses of statins given to healthy volunteers did not improve antibacterial effects of whole blood. Thus, a direct bactericidal effect of statins in vivo is probably not the mechanism behind the observed beneficial effect of statins against various infections.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. peter.bergman@ki.se
authors.forename: Peter
authors.initials: P
authors.lastname: Bergman
authors.forename: Charlotte
authors.initials: C
authors.lastname: Linde
authors.forename: Katrin
authors.initials: K
authors.lastname: Pütsep
authors.forename: Anton
authors.initials: A
authors.lastname: Pohanka
authors.forename: Staffan
authors.initials: S
authors.lastname: Normark
authors.forename: Birgitta
authors.initials: B
authors.lastname: Henriques-Normark
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Linda
authors.initials: L
authors.lastname: Björkhem-Bergman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016667:Bacterial Capsules / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D001936:Moraxella catarrhalis / Q000187:drug effects; D010406:Penicillins / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010406:Penicillins