Motos Ana, Yang Minlan, Battaglini Denise, Yang Hua, Meli Andrea, Bobi Joaquim, Cabrera Roberto, Tanzella Giacomo, Vargas Carmen Rosa, Arrieta Marta, Llonch Blanca, Rovira-Ribalta Nona, Barbeta Enric, di Giannatale Pierluigi, Nogas Stefano, Fernández-Barat Laia, Rigol Montserrat, Kiarostami Kasra, Martín-Loeches Ignacio, Vila Jordi, Martinez Daniel, Bassi Gianluigi Li, Torres Antoni
Pneumology Department, Hospital Clínic, Thorax Institute, Barcelona, Spain.
Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Intensive Care Med Exp. 2025 Feb 27;13(1):27. doi: 10.1186/s40635-025-00731-1.
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.
肺炎链球菌是社区获得性肺炎（CAP）的主要病因，通常采用β-内酰胺类、大环内酯类或喹诺酮类药物治疗。目前推荐使用皮质类固醇作为重症CAP的辅助治疗以改善预后。在这项前瞻性随机动物研究中，我们使用猪肺炎链球菌肺炎模型评估了各种抗生素方案联合皮质类固醇的杀菌效果。
在30头白色长白母猪中，通过支气管内接种大环内酯耐药肺炎链球菌19A分离株诱导肺炎。动物被随机分为接受生理盐水、头孢曲松（CRO）联合左氧氟沙星（LVX）、CRO联合阿奇霉素（AZM）或这些药物与甲泼尼龙（MP）的组合。主要结局指标为治疗48小时后肺组织中的肺炎链球菌浓度，结果显示CRO+LVX、CRO+AZM、CRO+LVX+MP和CRO+AZM+MP组在降低细菌载量方面同样有效。然而，仅在CRO+AZM+MP组实现了肺组织细菌的完全清除。次要结局指标，包括气管吸出物和支气管肺泡灌洗（BAL）样本中的细菌负荷，显示所有治疗组的杀菌活性相似。CRO+AZM+MP组表现出最受控制的炎症反应，炎症达到基线水平，而其他组的炎症标志物升高。
尽管使用的是大环内酯耐药肺炎链球菌分离株，但与其他抗生素组合相比，CRO、AZM和MP的联合使用取得了相似甚至更好的结果。该方案兼具杀菌和免疫调节作用，表明其在治疗大环内酯耐药肺炎链球菌肺炎方面的有效性。
