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.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
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), Fundació La Marató de TV3 (201831-10), the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomedica En Red- Enfermedades Respiratorias (CIBERES) and BITRECS (IDIBAPS) 2019.
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R.A., G.L.B, A.M. and A.T. participated in the development of the protocol, study design, study management, statistical analysis and data interpretation and wrote the first draft of the report. L.F.B, E.A.X., M. Rigol, G.F., C.T., J.B., F.P., M.C., T.C., C.C., M.Y., H.Y., M.A., J.D.M., F.D.R., M.A.S., M. Rinaudo and S.T. participated in data collection and interpretation and critically reviewed the first draft of the report. M.J.S., D.P.N., A.A. and J.R. participated in study design and reviewed the report.
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A.T. has received grants from MedImmune, Cubist, Bayer, Theravance and Polyphor and personal fees as an advisory board member from Bayer, Roche, The Medicines CO and Curetis. He has received personal fees as a member of the speaker’s bureau from GSK, Pfizer, Astra Zeneca and Biotest Advisory Board, outside the submitted work. None of the other authors have any competing interests with the current publication.
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Amaro, R., Li Bassi, G., Motos, A. et al. Development and characterization of a new swine model of invasive pneumococcal pneumonia. Lab Anim 50, 327–335 (2021). https://doi.org/10.1038/s41684-021-00876-y
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DOI: https://doi.org/10.1038/s41684-021-00876-y
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