Studies on the Antibacterial Effects of Statins - In Vitro and In Vivo

被引:68
作者
Bergman, Peter [1 ,2 ]
Linde, Charlotte [3 ]
Putsep, Katrin [3 ]
Pohanka, Anton [5 ]
Normark, Staffan [3 ]
Henriques-Normark, Birgitta [3 ,4 ]
Andersson, Jan [2 ]
Bjorkhem-Bergman, Linda [5 ]
机构
[1] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Lab Med,Div Clin Microbiol, Stockholm, Sweden
[2] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Med,Ctr Infect Med CIM, Stockholm, Sweden
[3] Karolinska Inst, Microbiol & Tumorbiol Ctr MTC, Stockholm, Sweden
[4] Karolinska Univ Hosp, Stockholm, Sweden
[5] Karolinska Univ Hosp, Karolinska Inst, Div Clin Pharmacol, Dept Lab Med, Stockholm, Sweden
来源
PLOS ONE | 2011年 / 6卷 / 08期
关键词
STREPTOCOCCUS-PNEUMONIAE; DISEASE;
D O I
10.1371/journal.pone.0024394
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Aim: 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). Findings: The MIC-value for simvastatin against S pneumoniae and M catarrhalis was 15 mu g/mL (36 mmol/L). Fluvastatin and Pravastatin showed no antibacterial effect in concentrations up to 100 mu g/mL (230 mu mol/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 mu g/mL (36 mu mol/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.
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