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A Contemporary Warming/Restraining Device for Efficient Tail Vein Injections in a Murine Fungal Sepsis Model
Published on: November 6, 2020
Mice with disseminated candidiasis die of progressive sepsis
Brad Spellberg1, Ashraf S Ibrahim, John E Edwards
1Los Angeles Biomedical Research Institute, Division of Infectious Diseases at Harbor-University of California at Los Angeles Medical Center, Torrance 90502, USA. bspellberg@labiomed.org
Background:
Candida species are among the most common etiologies of nosocomial bloodstream infections, causing a mortality of >40%. The murine model of hematogenously disseminated candidiasis is the standard for investigating both the activity of antifungal agents and the pathogenesis of this disease. However, despite decades of use, little is known about the physiological characteristics of the host in this model, and the cause of death remains unclear.
Methods:
Using i-STAT technology, we measured blood chemistry and hemodynamic parameters to define host physiological characteristics during murine disseminated candidiasis.
Results:
Mice with hematogenously disseminated candidiasis died of progressive sepsis, as manifested by worsening hypotension, tachycardia, and hypothermia. The mice developed metabolic acidosis, as well as profound acidemia and hypoglycemia. They also developed renal insufficiency, which became severe only shortly before death. Kidney fungal burden was correlated with severity of renal failure and systemic acidosis. The presence of significant weight loss, hypotension, or hypothermia was predictive of imminent death.
Conclusions:
These findings indicate that the murine model of hematogenously disseminated candidiasis accurately recapitulates the progressive sepsis seen during severe clinical cases. The results underscore the validity of the model for study of the pathophysiological aspects of this disease, as well as for the evaluation of antifungal drug efficacy.
Insights
This study reveals that mice with disseminated candidiasis develop progressive sepsis, characterized by organ dysfunction and metabolic derangements, accurately modeling human infections. These findings validate the murine model for studying candidiasis pathogenesis and antifungal drug efficacy.
Area of Science:
- Infectious Diseases
- Mycology
- Animal Models
Background:
- Candida species cause significant nosocomial bloodstream infections with high mortality.
- The murine model of disseminated candidiasis is crucial for studying antifungal agents and disease pathogenesis.
- Limited understanding of host physiology and cause of death in this model exists.
Purpose of the Study:
- To define host physiological characteristics in the murine model of disseminated candidiasis.
- To elucidate the cause of death in this standard experimental model.
Main Methods:
- Utilized i-STAT technology to measure blood chemistry and hemodynamic parameters.
- Assessed physiological changes in mice during hematogenously disseminated candidiasis.
Main Results:
- Mice exhibited progressive sepsis with hypotension, tachycardia, and hypothermia.
- Metabolic acidosis, acidemia, and hypoglycemia were observed.
- Renal insufficiency correlated with fungal burden and acidosis; weight loss, hypotension, and hypothermia predicted death.
Conclusions:
- The murine model accurately reflects progressive sepsis in severe human candidiasis.
- Findings validate the model for investigating candidiasis pathophysiology.
- The model is suitable for evaluating antifungal drug efficacy.
