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

TL;DR

This study tests antibiotic and corticosteroid combinations in a pig model of pneumonia caused by macrolide-resistant Streptococcus pneumoniae.

Contribution

The study identifies a combination of ceftriaxone, azithromycin, and methylprednisolone as most effective for treating macrolide-resistant pneumococcal pneumonia.

Findings

The CRO + AZM + MP group achieved complete bacterial eradication from lung tissue.

This treatment group also showed the most controlled inflammatory response.

Other antibiotic combinations did not achieve complete eradication despite similar bactericidal activity.

Abstract

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.

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.

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.

The online version contains supplementary material available at 10.1186/s40635-025-00731-1.

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