Antimicrobial effect of statins: organic solvents might falsify microbiological testing results

Objectives: Statins possess a variety of pleiotropic effects. Direct antimicrobial effect of simvastatin and, to a smaller degree, fluvastatin, has been reported for Gram-positive bacteria. The present study investigated antimicrobial activity of all statins available on the European market on Gram-positive and -negative organisms, with particular attention on the possible impact of organic solvents on bacterial growth. Methods: Simvastatin was dissolved both in 100% methanol (simvastatin(100%)) and in 5% methanol (simvastatin(5%)), the latter solution requiring pH adjustment for solubility reasons. Antimicrobial activity of both simvastatin solutions and of five other statins was evaluated against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 29213 by broth microdilution testing. In addition, time-kill curves of methanol alone, simvastatin(100%) and simvastatin(5%) were performed for S. aureus ATCC 29213. Results: Relevant antimicrobial activity was observed only for simvastatin(100%) when tested against S. aureus (MIC = 31 mg/l). MIC of simvastatin(5%) was more than 10-fold higher (500 mg/l). In analogy, time-kill rates of simvastatin against S. aureus decreased markedly when the methanol content in the test solutions was reduced. In both experimental settings, antimicrobial activity observed for pure methanol was only slightly inferior to that of simvastatin(100%). Conclusion: Previously published results about the antimicrobial effect of statins relied on the use of pure methanol as solvent. Present data indicate that the observed antimicrobial effect must be attributed, at least to a very large extent, to the solvent. Toxicity of solvents may influence microbiological evaluation of poorly water-soluble substances. pH adjustment to enhance solubility and thus reduce the need for using organic solvent might sometimes overcome this problem.