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Background <p><i>Streptococcus pneumoniae</i>, a primary cause of community-acquired pneumonia (CAP), is typically treated with β-lactams and macrolides or quinolones. Corticosteroids are now recommended as adjunctive therapy in severe CAP to improve outcomes. <b>I</b>n this prospective randomized animal study, we evaluated the bactericidal efficacy of various antibiotic regimens combined with corticosteroids using a porcine pneumococcal pneumonia model.</p> Results <p>In 30 White-Landrace female pigs, pneumonia was induced by intrabronchial inoculation of macrolide-resistant <i>S. pneumoniae</i> 19A isolate. Animals were randomized to receive saline, ceftriaxone (CRO) with levofloxacin (LVX), CRO with azithromycin (AZM), or combinations of these with methylprednisolone (MP). The primary outcome, <i>S. pneumoniae</i> concentrations in lung tissue after 48&#xa0;h of treatment, showed that the CRO + LVX, CRO + AZM, CRO + LVX + MP, and CRO + AZM + MP groups were equally effective in reducing bacterial load. However, complete bacterial eradication from lung tissue was achieved only in the CRO + AZM + MP group. Secondary outcomes, including bacterial burden in tracheal aspirates and bronchoalveolar lavage (BAL) samples, showed similar bactericidal activity across all treatment groups. The CRO + AZM + MP group demonstrated the most controlled inflammatory response, achieving baseline levels of inflammation, while other groups exhibited elevated inflammatory markers.</p> Conclusions <p>Despite using a macrolide-resistant <i>S. pneumoniae</i> isolate, the combination of CRO, AZM, and MP achieves similar or even superior results compared to other antibiotic combinations. This regimen provides both bactericidal and immunomodulatory benefits, suggesting its effectiveness in treating macrolide-resistant <i>S. pneumoniae</i> pneumonia.</p>

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Corticosteroid and antimicrobial therapy in macrolide-resistant pneumococcal pneumonia porcine model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月27日

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  • Ana Motos,
  • Minlan Yang,
  • Denise Battaglini,
  • Hua Yang,
  • Andrea Meli,
  • Joaquim Bobi,
  • Roberto Cabrera,
  • Giacomo Tanzella,
  • Carmen Rosa Vargas,
  • Marta Arrieta,
  • Blanca Llonch,
  • Nona Rovira-Ribalta,
  • Enric Barbeta,
  • Pierluigi di Giannatale,
  • Stefano Nogas,
  • Laia Fernández-Barat,
  • Montserrat Rigol,
  • Kasra Kiarostami,
  • Ignacio Martín-Loeches,
  • Jordi Vila,
  • Daniel Martinez,
  • Gianluigi Li Bassi,
  • Antoni Torres

摘要

Background

Streptococcus pneumoniae, a primary cause of community-acquired pneumonia (CAP), is typically treated with β-lactams and macrolides or quinolones. Corticosteroids are now recommended as adjunctive therapy in severe CAP to improve outcomes. In this prospective randomized animal study, we evaluated the bactericidal efficacy of various antibiotic regimens combined with corticosteroids using a porcine pneumococcal pneumonia model.

Results

In 30 White-Landrace female pigs, pneumonia was induced by intrabronchial inoculation of macrolide-resistant S. pneumoniae 19A isolate. Animals were randomized to receive saline, ceftriaxone (CRO) with levofloxacin (LVX), CRO with azithromycin (AZM), or combinations of these with methylprednisolone (MP). The primary outcome, S. pneumoniae concentrations in lung tissue after 48 h of treatment, showed that the CRO + LVX, CRO + AZM, CRO + LVX + MP, and CRO + AZM + MP groups were equally effective in reducing bacterial load. However, complete bacterial eradication from lung tissue was achieved only in the CRO + AZM + MP group. Secondary outcomes, including bacterial burden in tracheal aspirates and bronchoalveolar lavage (BAL) samples, showed similar bactericidal activity across all treatment groups. The CRO + AZM + MP group demonstrated the most controlled inflammatory response, achieving baseline levels of inflammation, while other groups exhibited elevated inflammatory markers.

Conclusions

Despite using a macrolide-resistant S. pneumoniae isolate, the combination of CRO, AZM, and MP achieves similar or even superior results compared to other antibiotic combinations. This regimen provides both bactericidal and immunomodulatory benefits, suggesting its effectiveness in treating macrolide-resistant S. pneumoniae pneumonia.