Studies on the antibacterial effects of statins--in vitro and in vivo

• Published in: PloS one Vol. 6; no. 8; p. e24394
• Main Authors: Bergman, Peter, Linde, Charlotte, Pütsep, Katrin, Pohanka, Anton, Normark, Staffan, Henriques-Normark, Birgitta, Andersson, Jan, Björkhem-Bergman, Linda
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.08.2011; Public Library of Science (PLoS)
• Subjects: Analysis; Anti-Bacterial Agents - pharmacology; Antibiotics; Antiinfectives and antibacterials; Antilipemic agents; Bacteria; Bacterial Capsules - metabolism; Bacterial infections; Biosynthesis; Blood; Blood culture; Blood tests; Drug dosages; Drug Synergism; Enzymes; Experiments; Fluvastatin; Genomes; Health aspects; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; In vivo methods and tests; Infections; Laboratories; Medical research; Medicin och hälsovetenskap; Medicine; Microbial Sensitivity Tests; Microbial Viability - drug effects; Microorganisms; Minimum inhibitory concentration; Moraxella (Branhamella) catarrhalis - drug effects; Neutrophils; Penicillin; Penicillins; Penicillins - pharmacology; Pneumonia; Pravastatin; Respiratory tract; Respiratory tract diseases; Sickle cell disease; Simvastatin; Staphylococcus aureus; Statins; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - growth & development; Streptococcus pneumoniae - metabolism; Studies; Synergistic effect; Viability; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024394

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. The aim of the present study was to elucidate possible antibacterial effects of statins against primary pathogens of the respiratory tract. 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). 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. 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.