[ODP7A] a. Antimicrobial Agents

[ODP-200] The therapeutic effect of hinokitiol on the murine model of pneumococcal pneumonia

○Toshihito Isono¹, Hisanori Domon^1,2, Tomoki Maekawa^1,2, Hikaru Tamura^1,2, Takumi Hiyoshi¹, Katsunori Yanagihara³, Eiji Kunitomo⁴, Yutaka Terao^1,2 (¹Div. Microbiol. Infect. Dis., Niigata Univ. Grad. Sch. Med. & Dent. Sci., ²Cent. for Adv. Oral Sci., Niigata Univ. Grad. Sch. Med. & Dent. Sci., ³Dept. Laboratory Medicine, Nagasaki Univ. Grad. Sch. Biomed., ⁴Central R&D Lab., Kobayashi Pharma.)

Objectives: Streptococcus pneumoniae is the main cause of community-acquired pneumonia. Recently, antimicrobial resistance of pneumococcus has raised the risk of disease. Our previous study has shown that hinokitiol, which is isolated from the cypress family, has been exhibited antibacterial activity against S. pneumoniae in vitro regardless of antimicrobial resistance. In this study, the efficacy of hinokitiol was investigated in a mouse pneumonia model.
Methods & results: BALB/c mice were intratracheally infected with S. pneumoniae strain D39 (antimicrobial susceptible) or strain NU4471 (macrolide-resistant). After 1 h, hinokitiol was injected via the tracheal route using MicroSprayer Aerosolizer. After 18 h from infection, bronchoalveolar lavage fluid (BALF) and serum, lung tissue samples were collected. Hinokitiol treatment significantly decreased the number of S. pneumoniae in the BALF and the concentration of pneumococcal DNA in the serum, regardless of whether bacteria were resistant or susceptible to macrolides. In addition, hinokitiol decreased the number of neutrophils and the cytokine levels in the BALF.
Discussion: Our findings suggested that intratracheal administration of hinokitiol reduced bacterial load and suppressed excessive host immune response in the pneumonia mouse model. Thus, hinokitiol could be a candidate for the treatment of pneumococcal pneumonia.