Effects of macrolides against pneumolysin of macrolide-resistant Streptococcus pneumoniae

¹ Second Dept of Internal Medicine
² Second Dept of Internal Medicine; and Dept of Pharmacotherapeutics, Nagasaki University Graduate School of Pharmaceutical Sciences
³ Second Dept of Internal Medicine; and Division of Molecular & Clinical Microbiology, Dept of Molecular Microbiology & Immunology, Nagasaki University Graduate School of Medical Sciences, NAGASAKI, JAPAN

^* To whom correspondence should be addressed. E-mail: kyana-ngs{at}umin.ac.jp.

	Abstract

To clarify the discrepancy between increasing resistance and conservative clinical effects of macrolides against macrolide-resistant S. pneumoniae, we evaluated the effects of sub-MIC of macrolides on pneumolysin.

In vitro, S. pneumoniae was incubated with 1, 2 and 4 µg·ml^-1 of clarithromycin and azithromycin for 8 hours. Then, western blot analysis and hemolytic assay were performed to examine the production and activities of pneumolysin. In vivo, mice were infected with the S. pneumoniae intranasally and treated with clarithromycin (40 or 200 mg·kg^-1 twice daily) or azithromycin (40 or 200 mg·kg^-1 once daily) orally for 7 days. After 72 hours postinfection, western blot analysis was performed to examine pneumolysin production in lungs. Furthermore, survival rates were observed for 10 days.

In vitro, every concentrations of macrolides inhibited pneumolysin production more than the control. Furthermore, clarithromycin (2, 4 µg·ml^-1) and azithromycin (4 µg·ml^-1) reduced the pneumolysin activities more than the control. In vivo, macrolides (200 mg·kg^-1) reduced pneumolysin in murine lungs more than the control. Furthermore, clarithromycin (40 and 200 mg·kg^-1) and azithromycin (200 mg·kg^-1) improved the survival rates more than the control.

These results showed that sub-MIC of macrolides reduced pneumolysin. It might be related with the effectiveness of macrolides against pneumonia caused by high-level MRSP. The further investigations are necessary to evaluate the effects of macrolides against MRSP.

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