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We deeply thank Francesc Marco (Microbiology Department, Hospital Clinic) for his swift and valuable support in identifying and providing human S. pneumoniae strains upon study commencement. In addition, we acknowledge the healthcare providers from the pulmonary intensive care unit at Hospital Clinic, Barcelona for all their encouragement during these studies. Support was provided by the Instituto de Salud Carlos III de Madrid (Spain) (FIS PI15/00506), Fundacio La Marato de TV3 (201831-10), the Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica En Red- Enfermedades Respiratorias (CIBERES) and BITRECS (IDIBAPS) 2019.

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Development and characterization of a new swine model of invasive pneumococcal pneumonia

Publicated to:Lab Animal. 50 (11): 327-+ - 2021-11-01 50(11), DOI: 10.1038/s41684-021-00876-y

Authors: Amaro, R; Li Bassi, G; Motos, A; Fernandez-Barat, L; Xiol, EA; Rigol, M; Travierso, C; Bobi, J; Carbonara, M; Comaru, T; Chiurazzi, C; Yang, ML; Yang, H; Arrieta, M; Marti, JD; De Rosa, F; Rinaudo, M; Terraneo, S; Torres, A; Artigas, A; Frigola, G; Saco, MA; Ramirez, J; Pagliara, F; Schultz, MJ; Nicolau, DP

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Abstract

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 × 105 ± 2 × 102 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.© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

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