Characterization of an Animal Model of Ventilator-Acquired Pneumonia

Marquette, Charles-Hugo; Wermert, Delphine; Wallet, Frédéric; Copin, Marie‐Christine; Tonnel, André‐Bernard

doi:10.1378/chest.115.1.200

Cited by 55 publications

(60 citation statements)

References 21 publications

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“…Thus, in this review, the main characteristics of the most used P. aeruginosa pneumonia animal models for acute pneumonia, VAP and chronic pneumonia occurring in CF patients are summarized and compared ( Table 1). Several different species have been used to model human pneumonia including piglets (28)(29)(30), rodents (31)(32)(33), primates (34,35), sheep (36,37), dogs (38,39) and rabbits (40,41) and these models have proven instructive in studies of disease mechanisms and in antibiotic testing. Nonetheless, rodents have been the preferred choice in translational pulmonary research as they not only are in accordance with the 3R principles of animal experimentation (42) but also offer specific advantages such as the potential to validate key findings or elucidate distinct pathogenic steps in a wide range of developed transgenic rodent models that are available to the scientific community.…”

Section: Need For Animal Modelingmentioning

confidence: 99%

“…The control MV and sterile beads only cause a mild inflammation evidenced by increased cellular infiltrates that for sterile bead inoculated animals are restricted to areas surrounding the beads (see insets). (29). Recently, a porcine P. aeruginosa VAP model was established via oropharyngeal challenge immediately after intubation and a second challenge 4 hours into ventilation using a ceftriaxone-resistant P. aeruginosa strain to ensure pulmonary aspiration of oropharyngeal secretions caused by the desired organism (28).…”

Section: Types Of Pneumonia Modelsmentioning

confidence: 99%

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Animal models of hospital-acquired pneumonia: current practices and future perspectives

Bielen¹,

Jongers²,

Malhotra-Kumar³

et al. 2017

Ann. Transl. Med.

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Lower respiratory tract infections are amongst the leading causes of mortality and morbidity worldwide. Especially in hospital settings and more particularly in critically ill ventilated patients, nosocomial pneumonia is one of the most serious infectious complications frequently caused by opportunistic pathogens.Pseudomonas aeruginosa is one of the most important causes of ventilator-associated pneumonia as well as the major cause of chronic pneumonia in cystic fibrosis patients. Animal models of pneumonia allow us to investigate distinct types of pneumonia at various disease stages, studies that are not possible in patients.Different animal models of pneumonia such as one-hit acute pneumonia models, ventilator-associated pneumonia models and biofilm pneumonia models associated with cystic fibrosis have been extensively studied and have considerably aided our understanding of disease pathogenesis and testing and developing new treatment strategies. The present review aims to guide investigators in choosing appropriate animal pneumonia models by describing and comparing the relevant characteristics of each model using P. aeruginosa as a model etiology for hospital-acquired pneumonia. Key to establishing and studying these animal models of infection are well-defined end-points that allow precise monitoring and characterization of disease development that could ultimately aid in translating these findings to patient populations in order to guide therapy. In this respect, and discussed here, is the development of humanized animal models of bacterial pneumonia that could offer unique advantages to study bacterial virulence factor expression and host cytokine production for translational purposes.

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Section: Need For Animal Modelingmentioning

confidence: 99%

Section: Types Of Pneumonia Modelsmentioning

confidence: 99%

Animal models of hospital-acquired pneumonia: current practices and future perspectives

Bielen¹,

Jongers²,

Malhotra-Kumar³

et al. 2017

Ann. Transl. Med.

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“…MARQUETTE et al [20] have standardised an animal model of pneumonia in ventilated piglets. This model closely resembles human pneumonia and has proven to be very useful for evaluating different aspects related to the diagnosis and treatment of severe pneumonia [21][22][23][24][25][26][27].…”

mentioning

confidence: 99%

Effects of glucocorticoids in ventilated piglets with severe pneumonia

Sibila¹,

Luna²,

Agustı́³

et al. 2008

European Respiratory Journal

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There is clinical evidence suggesting that glucocorticoids may be useful in severe pneumonia, but the pathogenic mechanisms explaining these beneficial effects are unknown.The aim of the present study was to determine the effects of adding glucocorticoids to antibiotic treatment in an experimental model of severe pneumonia.In total, 15 Lagerwhite-Landrace piglets were ventilated for 96 h. After intubation, a 75 mL solution containing Pseudomonas aeruginosa (10 6 cfu?mL -1 ) was bronchoscopically inoculated.The animals were randomised into three groups 12 h after inoculation: 1) untreated; 2) treated with ciprofloxacin; and 3) treated with ciprofloxacin plus methylprednisolone. Physiological and laboratory parameters were monitored throughout the study. Pro-inflammatory cytokines were measured in serum and bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed. At the end of the study, piglets receiving the antibiotic plus glucocorticoids showed: 1) a decrease in the concentration of interleukin-6 in BAL; and 2) a decrease in the global bacterial burden both in BAL and lung tissue.In conclusion, in this experimental model of pneumonia, the association of glucocorticoids with antibiotics attenuates local inflammatory response and decreases bacterial burden in the lung.

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“…Animal models could help to clarify this issue. MARQUETTE et al [7] have developed an animal model of pneumonia in mechanically ventilated piglets that closely resembles severe human pneumonia. This model has proved to be very useful for the proper evaluation of different aspects regarding diagnosis and treatment [8][9][10][11][12][13].…”

mentioning

confidence: 99%

Experimental Pseudomonas aeruginosa pneumonia: evaluation of the associated inflammatory response

Sibila¹,

Agustı́²,

Torres³

et al. 2007

European Respiratory Journal

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An abnormal inflammatory response (IR) in pneumonia is associated with poor outcomes and high mortality. Animal models could help to better understand the relationship between the pulmonary infection and the associated IR. The aims of the present study were to validate an experimental model of pneumonia induced by the inoculation of Pseudomonas aeruginosa in ventilated piglets and to study the associated IR over a long period of time (96 h).Five Lagerwhite-Landrace piglets were ventilated for 4 days. After intubation, a solution containing 75 mL of P. aeruginosa (10 6 colony-forming units?mL) was bronchoscopically inoculated. Physiological and laboratory parameters were monitored throughout the study. Proinflammatory cytokines were measured in serum and in bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed.All the animals developed histopathological evidence of pneumonia. Microbiological studies of both BAL and lung confirmed the presence of P. aeruginosa in all the samples. Throughout the study, an increase in interleukin-6 was observed in serum and in BAL.In conclusion, the experimental model of pneumonia induced by the inoculation of high concentrations of Pseudomonas aeruginosa in ventilated piglets is feasible and could be appropriate for the evaluation of different aspects of the associated inflammatory response.

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Characterization of an Animal Model of Ventilator-Acquired Pneumonia

Cited by 55 publications

References 21 publications

Animal models of hospital-acquired pneumonia: current practices and future perspectives

Animal models of hospital-acquired pneumonia: current practices and future perspectives

Effects of glucocorticoids in ventilated piglets with severe pneumonia

Experimental Pseudomonas aeruginosa pneumonia: evaluation of the associated inflammatory response

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