2557. Development of Rabbit Models of Ventilator-Associated Carbapenem-Resistant Acinetobacter baumannii Pneumonia

BACKGROUND: Carbapenem-resistant (CR) Gram-negative bacteria are emerging worldwide as global public health threats. Mortality rates from these pathogens are especially high in immunocompromised patients. Ventilator-associated bacterial pneumonia (VABP) is among the most intractable of CR Gram-negative bacterial infections. We therefore aimed to develop rabbit animal models of VABP caused by CR strains of Acinetobacter baumannii. METHODS: Persistently neutropenic NZW rabbits were used throughout the study. A novel endotracheal tracheostomy system was developed for intubation. The early-phase intubated model (0-24h) received mechanical ventilation, while the late-phase intubated model (72-96h) was ambulatory. Ventilators were set to FiO(2)=40% and PEEP=8mmHg. The following outcome variables were assessed: survival, residual tissue bacterial burden (log CFU/g), residual BAL bacterial burden (log CFU/mL), lung weights, pulmonary lesion score, histology, pulse O(2) saturation, radiographic imaging, pro-inflammatory cytokines, quantitative tissue and BAL PCR, and histology. RESULTS: Within the first 12h post-inoculation, mean bacterial burdens in lung tissue and BAL fluid, respectively, which were established at approximately 10(6) CFU/g and 10(5) CFU/mL, persisted through 24h in the early-phase model and were increased in the late-phase model (72-96h) to approximately 10(7) CFU/g, and 10(6) CFU/mL. Mean Max SpO(2) was ≥99 mmHg and mean nadir SpO(2) was ≥74 mmHg. Serial thoracic radiographs over the course of 12-96h demonstrated progressive multilobar pneumonic infiltrates, while lung histology revealed progressive development of focal bronchopneumonia, intra-alveolar hemorrhage, alveolar epithelial cell necrosis, macrophage activation, monocytic infiltration, alveolar septal disruption, and microcolonies of bacteria. CONCLUSION: The new rabbit model of VABP produced by CR A. baumannii recapitulates the pathophysiological, microbiological, diagnostic imaging, and histological patterns of human disease by which to assess critically needed new antimicrobial agents against this lethal infection. DISCLOSURES: All Authors: No reported disclosures