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

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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.


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Peritoneal Lavage bacterial CFUs day 5 post-CLP.Mice were euthanized at day 5 post-CLP and the peritoneum lavaged and cultured. There were no significant differences in the number of bacterial colony forming units. Individual data points are show as well as the mean ± SEM, n = 6–7 mice per group.
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pone.0163005.g004: Peritoneal Lavage bacterial CFUs day 5 post-CLP.Mice were euthanized at day 5 post-CLP and the peritoneum lavaged and cultured. There were no significant differences in the number of bacterial colony forming units. Individual data points are show as well as the mean ± SEM, n = 6–7 mice per group.

Mentions: A significant question is whether the shorter antibiotic therapy would result in increased growth of bacteria. On day 5 post-CLP, peritoneal lavage fluid was tested for total CFUs, aerobic and anaerobic CFUs. While the 3-day treatment group showed slightly higher total and anaerobic CFU levels, these numbers were not significantly different (Fig 4).


Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality
Peritoneal Lavage bacterial CFUs day 5 post-CLP.Mice were euthanized at day 5 post-CLP and the peritoneum lavaged and cultured. There were no significant differences in the number of bacterial colony forming units. Individual data points are show as well as the mean ± SEM, n = 6–7 mice per group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036876&req=5

pone.0163005.g004: Peritoneal Lavage bacterial CFUs day 5 post-CLP.Mice were euthanized at day 5 post-CLP and the peritoneum lavaged and cultured. There were no significant differences in the number of bacterial colony forming units. Individual data points are show as well as the mean ± SEM, n = 6–7 mice per group.
Mentions: A significant question is whether the shorter antibiotic therapy would result in increased growth of bacteria. On day 5 post-CLP, peritoneal lavage fluid was tested for total CFUs, aerobic and anaerobic CFUs. While the 3-day treatment group showed slightly higher total and anaerobic CFU levels, these numbers were not significantly different (Fig 4).

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