Division of Animal Experimentation, Pneumology Department, Hospital Clinic, Barcelona, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Lab Anim (NY). 2021 Nov;50(11):327-335. doi: 10.1038/s41684-021-00876-y. Epub 2021 Oct 21.
Streptococcus pneumoniae is the most common microbial cause of community-acquired pneumonia. Currently, there are no available models of severe pneumococcal pneumonia in mechanically ventilated animals to mimic clinical conditions of critically ill patients. We studied endogenous pulmonary flora in 4 healthy pigs and in an additional 10 pigs in which we intra-bronchially instilled S. pneumoniae serotype 19 A, characterized by its resistance to penicillin, macrolides and tetracyclines. The pigs underwent ventilation for 72 h. All pigs that were not challenged with S. pneumoniae completed the 72-h study, whereas 30% of infected pigs did not. At 24 h, we clinically confirmed pneumonia in the infected pigs; upon necropsy, we sampled lung tissue for microbiological/histological confirmation of pneumococcal pneumonia. In control pigs, Streptococcus suis and Staphylococcus aureus were the most commonly encountered pathogens, and their lung tissue mean ± s.e.m. concentration was 7.94 ± 20 c.f.u./g. In infected pigs, S. pneumoniae was found in the lungs of all pigs (mean ± s.e.m. pulmonary concentration of 1.26 × 10 ± 2 × 10 c.f.u./g). Bacteremia was found in 50% of infected pigs. Pneumococcal pneumonia was confirmed in all infected pigs at 24 h. Pneumonia was associated with thrombocytopenia, an increase in prothrombin time, cardiac output and vasopressor dependency index and a decrease in systemic vascular resistance. Upon necropsy, microbiological/histological pneumococcal pneumonia was confirmed in 8 of 10 pigs. We have therefore developed a novel model of penicillin- and macrolide-resistant pneumococcal pneumonia in mechanically ventilated pigs with bacteremia and severe hemodynamic compromise. The model could prove valuable for appraising the pathogenesis of pneumococcal pneumonia, the effects associated with macrolide resistance and the outcomes related to the use of new diagnostic strategies and antibiotic or complementary therapies.
肺炎链球菌是社区获得性肺炎最常见的微生物病因。目前，尚无机械通气动物中严重肺炎链球菌肺炎的可用模型来模拟危重病患者的临床情况。我们研究了 4 头健康猪和另外 10 头猪的内源性肺部菌群，这些猪通过支气管内注入青霉素、大环内酯类和四环素耐药的 19A 型肺炎链球菌血清型进行了感染。这些猪接受了 72 小时的通气。所有未感染肺炎链球菌的猪都完成了 72 小时的研究，而 30%的感染猪没有完成。在 24 小时时，我们在感染猪中临床确诊了肺炎；尸检时，我们对肺部组织进行了采样，以进行微生物学/组织学确认肺炎链球菌肺炎。在对照猪中，猪链球菌和金黄色葡萄球菌是最常见的病原体，其肺部组织的平均 ± 标准误浓度分别为 7.94 ± 20 c.f.u./g。在感染猪中，所有猪的肺部都发现了肺炎链球菌（肺部平均 ± 标准误浓度为 1.26 × 10 ± 2 × 10 c.f.u./g）。50%的感染猪发生菌血症。在所有感染猪中，24 小时时都确认了肺炎链球菌肺炎。肺炎与血小板减少症、凝血酶原时间延长、心输出量和血管加压药依赖指数增加以及全身血管阻力降低有关。尸检时，10 头猪中有 8 头的肺部组织确认了微生物学/组织学肺炎链球菌肺炎。因此，我们在发生菌血症和严重血流动力学障碍的机械通气猪中建立了一种新的耐青霉素和大环内酯类肺炎链球菌肺炎模型。该模型可能对评估肺炎链球菌肺炎的发病机制、与大环内酯类耐药相关的影响以及与新的诊断策略、抗生素或补充治疗相关的结果非常有价值。
