The emergence of drug resistance with patient’s poor compliance, drugs adverse effects and the higher cost of therapy combinations, indicates a strong need for a therapy regimens with similar or higher antibiotics beneficial properties but with better adverse effects profiles. Results of the current study suggest a class effect antibacterial activity for statins, and indicate the superiority of the antibacterial activity of atorvastatin and simvastatin against several standard bacterial strains and clinical isolates as compared to rosuvastatin.
Statins were demonstrated to have pharmacological actions beyond their antihyperlipdimic properties including immunomodulatory, antioxidative and anticoagulant effects. A recent study indicated a direct antimicrobial effect of simvastatin and to a lesser extent fluvastatin against MSSA
]. Another study showed the antibacterial effect of atorvastatin and rosuvastatin in Gram + and Gram– bacteria [28
]. Results of the present study extend those of previous studies to include more agents of the statins family and test these agents against a wide range of standard bacterial strains and clinical isolates.
A very recent study has reported MIC values for simvastatin against S. pneumoniae
and M. catarrhalis
that are similar to the ones reported in this study [29
]. These MIC values reflect concentrations of statins that are higher than regular concentrations detected in human blood during statins therapy [30
However, since multiple dose statins are known for their favorable effect on the course of bacterial infections [18
], it is possible that statins undergoes accumulation at target human tissues upon multiple dosing, or there could a formation of relevant breakdown products in vivo
. Alternatively, statins could aid the action of other antibacterial agent during the treatment of infections in human through their reported pleiotropic actions [31
Statins induce their antihyperlipdimic, via inhibition of HMG-CoA reductase. In bacterial cells, HMG-CoA reductase is essential, where it is required for the biosynthesis of isoprenes [34
]. However, bacterial HMG-CoA reductase is of a different structural class with an affinity for statins that is 10 000 times weaker than the enzyme found in eukaryotes [34
]. Thus, it is unlikely that antibacterial activity of statins can be attributed to the known mechanism of action (i.e. inhibition of HMG-CoA reductase). Other possible mechanisms could be related to the pleiotropic properties of statins. For example, multiple statins including atorvastatin and simvastatin, were shown to be cytotoxic, to suppress cells growth, and to promote apoptosis [31
]. It is possible that the currently reported antibacterial activity of statins is related to such effects.
Results of the current study showed the superiority of the antibacterial effcets of atorvastatin or simvastatin to that of rosuvastatin. Previous studies have reported distinct effects, other than the antibacterial activity, for atorvastatin and simvastatin, compared to other members of statins [35
]. Additionally, our results show that atrovastatin was superior to simvastatin against VSE and VRE clinical isolates. These distinct effects could also be related to the differences in chemical structure among statins. For example, simvastatin is naturally product of fungal fermentation, whereas atorvastatin is a chemically synthesized derivative. Additionally, satins differ in their lipids affinity, thus, they could have different intrinsic activities. However, these points need more study, and could be a matter of future work.