Antimicrobial activity of simvastatin against chronic rhinosinusitis-related Staphylococcus aureus: an in vitro study

Abstract

Introduction: Staphylococcus aureus (S. aureus) in chronic rhinosinusitis (CRS), particularly when localised intracellularly, is linked to disease recalcitrance and poor post-surgical outcomes. Antibiotics frequently fail to penetrate the mammalian cell membrane, resulting in an inability to address the intracellular component of S. aureus. This contributes to treatment failure and development of antimicrobial resistance. We investigated the antimicrobial effects of simvastatin, a widely used, inexpensive medication with extracellular and intracellular antimicrobial properties, against CRS-related S. aureus.

Methods: simvastatin’s antimicrobial activity, in prodrug and hydroxylated forms, was assessed against S. aureus using the broth dilution method to determine the minimal inhibitory concentration (MIC). Intracellular activity of simvastatin was evaluated by pre-treating S. aureus -infected LAD2 mast cells with simvastatin and performing colony forming unit (CFU) enumeration and confocal microscopy. Cell viability was assessed using lactate dehydrogenase (LDH) assays.

Results: Simvastatin exhibited an extracellular MIC of 40 mmol/l against S. aureus. Intracellularly, it significantly reduced the bacterial burden by 46-fold in a dose-dependent manner between concentrations of 0.1-100 mmol/l. Toxicity to LAD2 cells was observed at 100 µmol/l. Confocal microscopy revealed a lower percentage of infected cells in the group pretreated with 30 µmol/l simvastatin (15.3%) compared to untreated cells (32.8%). Hydroxylated simvastatin demonstrated no antimicrobial activity against S. aureus.

Conclusions: simvastatin demonstrates in vitro antimicrobial activity against CRS-related S. aureus with the potential for repurposing as a novel antibiotic-sparing topical agent for the treatment of refractory CRS. This could improve surgical outcomes and reduce the risk of antimicrobial resistance.

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Identifiers

ORCID for S.P. Goldie: orcid.org/0000-0002-3912-9026

ORCID for A.F. Walls: orcid.org/0000-0003-4803-4595

ORCID for R.J. Salib: orcid.org/0000-0002-6753-7844

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