Abstract
BackgroundStatin 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.AimThe aim of the present study was to elucidate possible antibacterial effects of statins against primary pathogens of the respiratory tract.MethodsMIC-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).FindingsThe 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.ConclusionsSimvastatin 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.
Highlights
Statins (HMG-CoA reductase inhibitors) are today some of the most prescribed drugs in the world due to their beneficial effects on cardiovascular disease [1]
Simvastatin at high concentrations 15 mg/mL (36 mmol/L) rapidly kills S pneumoniae and M catarrhalis. 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
The antibacterial activity of Simvastatin was investigated using the encapsulated pneumococcal strain TIGR4. 100% killing of viable bacteria was obtained with simvastatin at the concentration 15.6 mg/mL (36 mmol/L) (Fig 1A)
Summary
Statins (HMG-CoA reductase inhibitors) are today some of the most prescribed drugs in the world due to their beneficial effects on cardiovascular disease [1]. During recent years statins have been ascribed additional beneficial (pleitropic) effects. This includes anti-inflammatory [2], immunomodulatory [3] and anticarcinogenic properties [4,5]. A number of observational studies support that statin treatment is associated with a better prognosis in severe bacterial infections [6,7]. According to a meta-analysis of these studies patients on statin therapy seem to have a better outcome of bacterial infections (OR 0.53, 95% CI 0.42–0.66). Of 15 observational studies on pneumonia and statins, 12 showed that statin-use was associated with a favourable outcome [6]. Statin treatment has been associated with a beneficial outcome on respiratory tract infections. Previous in vitro and in vivo experiments have indicated favorable effects of statins in bacterial infections
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