Repurposing simvastatin for treatment of Klebsiella pneumoniae infections: in vitro and in vivo study.

Simvastatin had minimum inhibitory concentrations of 32 to 128 µg/mL against Klebsiella pneumoniae isolates and hindered the biofilm-formation ability of 58.54% of the isolates. It considerably diminished the bacterial cell counts in the biofilms as revealed by scanning electron microscope. Also, qRT-PCR revealed a downregulation of the biofilm genes (bcsA, wza, and luxS) by simvastatin in 48.78% of the isolates. Moreover, simvastatin has significantly improved the survival of mice and decreased the burden of bacteria in the infected lungs. Also, the histological architecture was substantially improved in the simvastatin-treated group, as the alveolar sacs and bronchioles appeared normal with minimal collagen fiber deposition. The immunohistochemical studies exposed that the TNF-α, NF-kβ, and COX-2 immunostaining considerably declined in the simvastatin-treated group. Furthermore, ELISA exposed that both IL-1β and IL-6 were considerably diminished in the lungs of the simvastatin-treated group.