Efficacy of azithromycin in a mouse pneumonia model against hospital-acquired methicillin-resistant staphylococcus aureus

Yu Yamashita, Kentaro Nagaoka, Hiroki Kimura, Masaru Suzuki, Satoshi Konno, Tatsuya Fukumoto, Koji Akizawa, Norihito Kaku, Yoshitomo Morinaga, Katsunori Yanagihara

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The use of macrolides against pneumonia has been reported to improve survival; however, little is known about their efficacy against methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. In this study, we investigated the effect of azithromycin (AZM) and compared it with that of vancomycin (VCM) and daptomycin (DAP) in a murine model of MRSA pneumonia. Mice were infected with MRSA by intratracheal injection and then treated with AZM, VCM, or DAP. The therapeutic effect of AZM, in combination or not with the other drugs, was compared in vivo, whereas the effect of AZM on MRSA growth and toxin mRNA expression was evaluated in vitro. In vivo, the AZM-treated group showed significantly longer survival and fewer bacteria in the lungs 24 h after infection than the untreated group, as well as the other anti-MRSA drug groups. No significant decrease in cytokine levels (interleukin-6 [IL-6] and macrophage inflammatory protein-2 [MIP-2]) in bronchoalveolar lavage fluid or toxin expression levels (- hemolysin [Hla] and staphylococcal protein A [Spa]) was observed following AZM treatment. In vitro, AZM suppressed the growth of MRSA in late log phase but not in stationary phase. No suppressive effect against toxin production was observed following AZM treatment in vitro. In conclusion, contrary to the situation in vitro, AZM was effective against MRSA growth in vivo in our pneumonia model, substantially improving survival. The suppressive effect on MRSA growth at the initial stage of pneumonia could underlie the potential mechanism of AZM action against MRSA pneumonia.

Original languageEnglish (US)
Article numbere00149-19
JournalAntimicrobial Agents and Chemotherapy
Volume63
Issue number9
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Azithromycin
  • Methicillin-resistant Staphylococcus aureus
  • Murine model
  • Pneumonia

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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