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Updated: Jan 3, 2026
A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
[Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for types of infections and
Lixue Wang1, Chao Ren1, Renqi Yao1
1Trauma Research Center, Fourth Medical Center of the Chinese PLA General Hospital, Beijing 100048, China.
Objective:
Although the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review has not been done for preclinical models. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling reviewed the 260 most highly cited papers between 2003 and 2012 using sepsis models to create a series of recommendations. This Part II report provides recommendations for the types of infections and documentation of organ injury in preclinical sepsis models. Concerning the types of infections, the review showed that the cecal ligation and puncture model was used for 44% of the studies while 40% injected endotoxin. Recommendation #8 (numbered sequentially from Part I): endotoxin injection should not be considered as a model of sepsis; live bacteria or fungal strains derived from clinical isolates are more appropriate. Recommendation #9: microorganisms should replicate those typically found in human sepsis. Sepsis-3 states that sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, but the review of the papers showed limited attempts to document organ dysfunction. Recommendation #10: organ dysfunction definitions should be used in preclinical models. Recommendation #11: not all activities in an organ/system need to be abnormal to verify organ dysfunction. Recommendation #12: organ dysfunction should be measured in an objective manner using reproducible scoring systems. Recommendation #13: not all experiments must measure all parameters of organ dysfunction, but investigators should attempt to fully capture as much information as possible. These recommendations are proposed as "best practices" for animal models of sepsis.
Insights
This review of preclinical sepsis models recommends using live bacteria or fungal strains, not endotoxin, for infection modeling. It also stresses documenting organ dysfunction objectively in animal studies for better sepsis research.
Area of Science:
- * Preclinical Sepsis Modeling
- * Animal Models of Infection
- * Host Response to Pathogens
Background:
- * Clinical definitions and treatments for sepsis are regularly updated.
- * A systematic review of preclinical sepsis models and their best practices was lacking.
- * The Wiggers-Bernard Conference addressed this gap by reviewing highly cited preclinical sepsis studies.
Purpose of the Study:
- * To provide recommendations for improving preclinical sepsis models.
- * To establish best practices for infection types and organ dysfunction documentation in animal sepsis studies.
- * To align preclinical models with the Sepsis-3 definition of life-threatening organ dysfunction.
Main Methods:
- * Systematic review of 260 highly cited preclinical sepsis papers (2003-2012).
- * Analysis of infection models used, including cecal ligation and puncture (44%) and endotoxin injection (40%).
- * Evaluation of organ dysfunction documentation in reviewed studies.
Main Results:
- * Endotoxin injection is not considered a suitable model for sepsis.
- * Live bacteria or fungal strains from clinical isolates are recommended for modeling sepsis.
- * Limited documentation of organ dysfunction was observed in reviewed preclinical studies.
- * Objective and reproducible methods for measuring organ dysfunction are needed.
Conclusions:
- * Preclinical sepsis models should utilize clinically relevant microorganisms.
- * Organ dysfunction must be systematically documented using objective scoring systems.
- * These recommendations aim to enhance the validity and reproducibility of animal models of sepsis.
