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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.


Related in: MedlinePlus

Antibiotics+Fluids vs. Fluids alone survival.Mice receiving antibiotics plus fluid resuscitation versus fluids only have a significantly better survival following CLP. Mice received 5 days of antibiotic therapy post-cecal ligation and puncture (CLP) treatment with 1ml D5LR and the broad spectrum antibiotic imipenem-cilastatin (25 mg/kg) compared to septic mice receiving just 1 ml of D5LR for 5 days post-CLP. N = 7–10 mice per group. **p <0.01 comparing the two groups.
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pone.0163005.g001: Antibiotics+Fluids vs. Fluids alone survival.Mice receiving antibiotics plus fluid resuscitation versus fluids only have a significantly better survival following CLP. Mice received 5 days of antibiotic therapy post-cecal ligation and puncture (CLP) treatment with 1ml D5LR and the broad spectrum antibiotic imipenem-cilastatin (25 mg/kg) compared to septic mice receiving just 1 ml of D5LR for 5 days post-CLP. N = 7–10 mice per group. **p <0.01 comparing the two groups.

Mentions: The first experiment demonstrated that a 5 day treatment protocol post-CLP with imipenem-cilastatin and fluid resuscitation compared to fluids alone significantly improved survival (Fig 1), confirming the clinical studies that prompt and appropriate antibiotic therapy improves survival [6].


Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality
Antibiotics+Fluids vs. Fluids alone survival.Mice receiving antibiotics plus fluid resuscitation versus fluids only have a significantly better survival following CLP. Mice received 5 days of antibiotic therapy post-cecal ligation and puncture (CLP) treatment with 1ml D5LR and the broad spectrum antibiotic imipenem-cilastatin (25 mg/kg) compared to septic mice receiving just 1 ml of D5LR for 5 days post-CLP. N = 7–10 mice per group. **p <0.01 comparing the two groups.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5036876&req=5

pone.0163005.g001: Antibiotics+Fluids vs. Fluids alone survival.Mice receiving antibiotics plus fluid resuscitation versus fluids only have a significantly better survival following CLP. Mice received 5 days of antibiotic therapy post-cecal ligation and puncture (CLP) treatment with 1ml D5LR and the broad spectrum antibiotic imipenem-cilastatin (25 mg/kg) compared to septic mice receiving just 1 ml of D5LR for 5 days post-CLP. N = 7–10 mice per group. **p <0.01 comparing the two groups.
Mentions: The first experiment demonstrated that a 5 day treatment protocol post-CLP with imipenem-cilastatin and fluid resuscitation compared to fluids alone significantly improved survival (Fig 1), confirming the clinical studies that prompt and appropriate antibiotic therapy improves survival [6].

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&rsquo;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-1&beta;, 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.


Related in: MedlinePlus