Potent synergistic combination of rosuvastatin and levofloxacin against Staphylococcus aureus: in vitro and in vivo study

J Appl Microbiol. 2021 Jul;131(1):182-196. doi: 10.1111/jam.14968. Epub 2020 Dec 30.

Abstract

Aims: The present study aims to evaluate the capability of rosuvastatin to synergize with levofloxacin against Staphylococcus aureus.

Methods and results: Rosuvastatin inhibited the growth of S. aureus with minimum inhibitory concentration of 16 μg ml-1 . Additionally, it showed a bactericidal effect at 4x minimum inhibition concentration. Using a checkerboard method, a synergistic effect was recorded when rosuvastatin was combined with levofloxacin showing against S. aureus isolate 28 (S 28). Furthermore, this combination was also able to display a significant reduction in biofilm formation (92·8%) and suppress the production of coagulase and β-haemolysin, and virulence factors of S. aureus isolate 28. An animal model for wound infection was used to assess the therapeutic effect of the test combination, in vivo. It was found that the test combination reduced the bacterial burden in the infected wounds by 91·3%. Pathological and histological analyses have revealed a decline in cell infiltration in the excisional wound skin tissue after treatment with rosuvastatin and levofloxacin combination.

Conclusions: Rosuvastatin combined with levofloxacin can be considered as a promising solution to combat S. aureus antibiotic resistance phenomenon.

Significance and impact of the study: This study unveils the potential effect of rosuvastatin when used in combination with levofloxacin can be used as a topical antibacterial agent to treat S. aureus skin infections.

Keywords: biofilms; levofloxacin; resistance; rosuvastatin; staphylococci; virulence.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Toxins / metabolism
  • Biofilms / drug effects*
  • Coagulase / metabolism
  • Disease Models, Animal
  • Drug Combinations
  • Drug Resistance, Microbial
  • Drug Synergism
  • Hemolysin Proteins / metabolism
  • Levofloxacin / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Rosuvastatin Calcium / pharmacology*
  • Sphingomyelin Phosphodiesterase / metabolism
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / metabolism
  • Virulence Factors / metabolism
  • Wound Infection / drug therapy*
  • Wound Infection / microbiology

Substances

  • Anti-Bacterial Agents
  • Bacterial Toxins
  • Coagulase
  • Drug Combinations
  • Hemolysin Proteins
  • Virulence Factors
  • Levofloxacin
  • Rosuvastatin Calcium
  • Sphingomyelin Phosphodiesterase
  • hlb protein, Staphylococcus aureus