TY - JOUR
T1 - Development and characterization of a new swine model of invasive pneumococcal pneumonia
AU - Amaro, Rosanel
AU - Li Bassi, Gianluigi
AU - Motos, Ana
AU - Fernandez-Barat, Laia
AU - Aguilera Xiol, Eli
AU - Rigol, Montserrat
AU - Frigola, Gerard
AU - Travierso, Chiara
AU - Bobi, Joaquim
AU - Pagliara, Francesco
AU - Carbonara, Marco
AU - Comaru, Talitha
AU - Chiurazzi, Chiara
AU - Yang, Minlan
AU - Yang, Hua
AU - Arrieta, Marta
AU - Marti, Joan Daniel
AU - de Rosa, Francesca
AU - Saco, Maria Adela
AU - Rinaudo, Mariano
AU - Terraneo, Silvia
AU - Schultz, Marcus J.
AU - Nicolau, David P.
AU - Artigas, Antonio
AU - Ramirez, Jose
AU - Torres, Antoni
N1 - Funding Information: 1Division of Animal Experimentation, Pneumology Department, Hospital Clinic, Barcelona, Spain. 2Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 3Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CIBERES), Barcelona, Spain. 4Critical Care Research Group, Prince Charles Hospital, Chermside, Australia. 5University of Queensland, Brisbane, Australia. 6University of Barcelona, Barcelona, Spain. 7Department of Pathology, Hospital Clinic, Barcelona, Spain. 8Division of Pneumology, ASST Rhodense ‘Guido Salvini’ Hospital, Garbagnate Milanese, Italy. 9Department of Surgical Sciences and Integrated Diagnostics (DISC), IRCCS AOU San Martino IST, Genova, Italy. 10San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy. 11University of Milan, Milan, Italy. 12Instituto Federal Farroupilha, Santo Ângelo, Brasil (sponsored by CNPq), Santo Ângelo, Brazil. 13Humanitas Clinical and Research Center, Rozzano, Milan, Italy. 14Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. 15Center for Anti-Infective Research & Development, Hartford Hospital, Hartford, CT, USA. 16Pathophysiological Laboratory, Institut de Investigacion Parc Tauli, Corporació Sanitaria Universitaria Parc Tauli, Autonomous University of Barcelona, Sabadell, Barcelona, Spain. 17These authors contributed equally: Rosanel Amaro, Gianluigi Li Bassi, Ana Motos. ✉e-mail: atorres@clinic.cat Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85117459751&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41684-021-00876-y
DO - https://doi.org/10.1038/s41684-021-00876-y
M3 - Article
C2 - 34675433
SN - 0093-7355
VL - 50
SP - 327
EP - 335
JO - Lab Animal
JF - Lab Animal
IS - 11
ER -