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Updated: Mar 14, 2026
Design of Cecal Ligation and Puncture and Intranasal Infection Dual Model of Sepsis-Induced Immunosuppression
Published on: June 15, 2019
Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or
Kendra N Iskander1, Max Vaickus2, Elizabeth R Duffy2
1Department of Surgery, Boston University Medical Center, 88 East Newton Street, C 515, Boston, MA, 02118, United States of America.
Abstract:
Antimicrobial therapy for sepsis has beneficial effects, but prolonged use fosters emergence of resistant microorganisms, increases cost, and secondary infections. We tested whether 3 days versus 5 days of antibiotics in the murine model of cecal ligation and puncture (CLP) negatively influences outcomes. Following CLP mice were randomized to receive the antibiotic imipenem-cilastatin (25mg/kg) in dextrose 5% in Lactated Ringer's solution every 12 hours for either three or five days. Serial monitoring over 28 days included body weight, temperature, pulse oximetry, and facial vein sampling for hematological analysis and glucose. A separate group of mice were euthanized on post-CLP day 5 to measure cytokines and peritoneal bacterial counts. The first study examined no antimicrobial therapy and demonstrated that antibiotics significantly improved survival compared to fluids only (p = 0.004). We next tested imipenem-cilastatin therapy for 3 days versus 5 days. Body weight, temperature, glucose, and pulse oximetry measurements remained generally consistent between both groups as did the hematological profile. Pro-inflammatory plasma cytokines were comparable between both groups for IL-6, IL-1β, MIP-2 and anti-inflammatory cytokines IL-10, and TNF SRI. At 5 days post-CLP, i.e. 2 days after the termination of antibiotics in the 3 day group, there were no differences in the number of peritoneal bacteria. Importantly, shortening the course of antibiotics by 40% (from 5 days to 3 days) did not decrease survival. Our results indicate that reducing the duration of broad-spectrum antibiotics in murine sepsis did not increase inflammation or mortality.
Insights
Shortening antibiotic courses for sepsis from five to three days in mice did not negatively impact survival or increase inflammation. This finding suggests reduced antibiotic duration is a viable strategy for sepsis treatment.
Area of Science:
- Infectious Diseases
- Pharmacology
- Critical Care Medicine
Background:
- Prolonged antimicrobial therapy for sepsis can lead to antibiotic resistance, increased costs, and secondary infections.
- Optimizing antibiotic duration is crucial for effective sepsis management while minimizing adverse effects.
Purpose of the Study:
- To evaluate the impact of a 3-day versus a 5-day course of imipenem-cilastatin on outcomes in a murine model of sepsis induced by cecal ligation and puncture (CLP).
- To determine if reducing antibiotic duration affects survival, physiological parameters, inflammatory markers, or bacterial load in sepsis.
Main Methods:
- Mice underwent cecal ligation and puncture (CLP) and were randomized to receive imipenem-cilastatin for either 3 or 5 days.
- Outcomes were monitored over 28 days, including body weight, temperature, pulse oximetry, hematology, and glucose levels.
- Cytokine levels and peritoneal bacterial counts were assessed on post-CLP day 5.
Main Results:
- Survival rates were comparable between the 3-day and 5-day antibiotic groups.
- Physiological parameters (weight, temperature, glucose, pulse oximetry) and hematological profiles showed no significant differences between groups.
- Pro-inflammatory and anti-inflammatory cytokine levels, as well as peritoneal bacterial counts, were similar in both groups at day 5 post-CLP.
Conclusions:
- Reducing the duration of broad-spectrum antibiotic therapy for sepsis from 5 days to 3 days in this murine model did not compromise survival.
- Shorter antibiotic courses did not lead to increased inflammation or higher bacterial loads.
- These findings support the potential for de-escalating antibiotic duration in sepsis treatment to mitigate resistance and reduce costs.
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