Evaluation of the Roflumilast Effect Supplemented with Linezolid in Pleural Empyema in Rats Caused by Intrapleural Staphylococcus aureus Inoculation

Jpn J Infect Dis. 2020 Jan 23;73(1):1-7. doi: 10.7883/yoken.JJID.2019.164. Epub 2019 Aug 30.

Abstract

In addition to tube drains, pleural empyema is treated with antibiotics and anti-inflammatory drugs. We aimed to evaluate the anti-inflammatory activity of roflumilast combined with linezolid in a rat model of pleural empyema induced by Staphylococcus aureus. A total of 40 rats were divided into 7 groups: sham (n = 4), S. aureus inoculation (n = 6), S. aureus + 10 mg/kg linezolid (n = 6), S. aureus + 5 mg/kg roflumilast (n = 6), S. aureus + 10 mg/kg linezolid + 5 mg/kg roflumilast (n = 6), S. aureus + 10 mg/kg roflumilast (n = 6), and S. aureus + 10 mg/kg linezolid + 10 mg/kg roflumilast (n = 6). Animals were administered linezolid 1 h before and 12 h after inoculation with S. aureus. Roflumilast was administered orally as a single dose 30 min before inoculation with S. aureus. Compared to linezolid treatment alone, linezolid combined with 5 mg/kg roflumilast significantly improved TNF-α, IL-1β, vasodilation/congestion, and tissue/pleural polynuclear leukocyte (PNL) infiltration (p < 0.05). Linezolid combined with 10 mg/kg roflumilast also provided a significant improvement in TNF-α, IL-1β, IL-6, endothelin-1, vasodilation/congestion, mesothelial cell damage, lung tissue PNL, and pleural PNL compared to linezolid alone (p < 0.05). Due to its anti-inflammatory effects and significant impact on recovery, roflumilast can be used in conjunction with antibiotherapy for the treatment of pleural empyema.

Keywords: linezolid; lung tissue; pleural empyema; treatment.

MeSH terms

  • Aminopyridines / administration & dosage
  • Aminopyridines / therapeutic use*
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use
  • Benzamides / administration & dosage
  • Benzamides / therapeutic use*
  • Cyclopropanes / administration & dosage
  • Cyclopropanes / therapeutic use
  • Drug Therapy, Combination
  • Empyema, Pleural / drug therapy*
  • Empyema, Pleural / microbiology
  • Linezolid / administration & dosage
  • Linezolid / therapeutic use*
  • Lung / drug effects
  • Lung / microbiology
  • Lung / pathology
  • Male
  • Rats
  • Rats, Wistar
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus

Substances

  • Aminopyridines
  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Benzamides
  • Cyclopropanes
  • Roflumilast
  • Linezolid