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Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Survival Proportions.There was no significant survival difference between the 5 days versus 3 days treatment group following CLP. N = 27–28 mice per group. There is also no statistically significant difference between the survival of the 5 day mice in this group and the comparable group in Fig 1.
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pone.0163005.g005: Survival Proportions.There was no significant survival difference between the 5 days versus 3 days treatment group following CLP. N = 27–28 mice per group. There is also no statistically significant difference between the survival of the 5 day mice in this group and the comparable group in Fig 1.

Mentions: The major outcome of sepsis studies, especially in the clinical literature, is the 28-day all-cause mortality. There was no significant difference in survival between 5-day and 3-day treatment mice (Fig 5, p = 0.78). The mortality rate for both treatment groups post-CLP remained around 50%. In the 3-day imipenem group, 11 out of 28 died within 28 days, while 12 out of 27 mice in the 5-day imipenem group died within 28 days. Using a Log-rank (Mantel-Cox) Test, we compared the mortality of the ten mice in the 5-day treatment group for Fig 1 to the mortality of the 28 mice in the 5-day treatment group used for Fig 5 and found no statistical difference between their mortality (P = 0.49) highlighting the reproducibility of our CLP model. This comparison was done to address the National Institutes of Health initiative on data reproducibility [32].


Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality
Survival Proportions.There was no significant survival difference between the 5 days versus 3 days treatment group following CLP. N = 27–28 mice per group. There is also no statistically significant difference between the survival of the 5 day mice in this group and the comparable group in Fig 1.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036876&req=5

pone.0163005.g005: Survival Proportions.There was no significant survival difference between the 5 days versus 3 days treatment group following CLP. N = 27–28 mice per group. There is also no statistically significant difference between the survival of the 5 day mice in this group and the comparable group in Fig 1.
Mentions: The major outcome of sepsis studies, especially in the clinical literature, is the 28-day all-cause mortality. There was no significant difference in survival between 5-day and 3-day treatment mice (Fig 5, p = 0.78). The mortality rate for both treatment groups post-CLP remained around 50%. In the 3-day imipenem group, 11 out of 28 died within 28 days, while 12 out of 27 mice in the 5-day imipenem group died within 28 days. Using a Log-rank (Mantel-Cox) Test, we compared the mortality of the ten mice in the 5-day treatment group for Fig 1 to the mortality of the 28 mice in the 5-day treatment group used for Fig 5 and found no statistical difference between their mortality (P = 0.49) highlighting the reproducibility of our CLP model. This comparison was done to address the National Institutes of Health initiative on data reproducibility [32].

View Article: PubMed Central - PubMed

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.

No MeSH data available.