Table 1_A rabbit model of acute bacteremia and sepsis caused by vancomycin-resistant Enterococcus faecium.docx

BackgroundVancomycin-resistant Enterococcus faecium (VREF) is a leading cause of nosocomial bacteremia, with mortality rates exceeding 60%. Current animal models lack translational relevance due to the divergence in immune systems between rodents and humans.
ObjectivesTo establish a rabbit model of Enterococcus faecium infection for evaluating therapeutic regimes, specifically monoclonal antibody (mAb) therapy.
MethodsWe established a reproducible rabbit model of acute VREF bacteremia using New Zealand White rabbits (n = 20) intravenously challenged with 1 × 109 CFU/g of VREF (strain E155). The animals were divided into three groups: uninfected controls (n = 6), infected untreated (n = 7), and infected treated with mAb 8AP (n = 7). We histopathologically examined the kidneys, lungs, spleen, heart, and liver, and quantified bacterial loads. Plasma cytokine levels were measured to assess inflammatory responses.
ResultsInfected untreated rabbits exhibited significant weight loss, sustained fever (>40 °C, peaking at 39h), and 20% mortality within 12h. Systemic bacterial dissemination was confirmed in all organs examined, with the spleen showing the highest bacterial load and the liver exhibiting the most severe histopathological damage (necrosis and suppurative inflammation). The mAb 8AP treatment significantly improved clinical outcomes: heart and respiratory rates decreased, and body weight increased compared with untreated infected rabbits. Cytokine profiling showed elevated levels of IL-6, IL-8, and IL-10, consistent with systemic inflammatory response syndrome (SIRS), with the mAb treatment showing a trend toward immune modulation.
ConclusionsThis model successfully simulates human VREF bacteremia and demonstrates the therapeutic potential of mAb 8AP. The rabbit model provides a clinically relevant platform for evaluating novel immunotherapies for VREF infections.