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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.


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Physiological Parameters.There were no physiological differences between mice receiving 5 days of imipenem-cilastatin treatment versus 3 days of treatment following CLP. Data expressed as mean ± SEM (n = 16–22 mice per group for body weight, temperature, and blood glucose measurement. N = 6 mice per group for pulse oximetry).
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pone.0163005.g002: Physiological Parameters.There were no physiological differences between mice receiving 5 days of imipenem-cilastatin treatment versus 3 days of treatment following CLP. Data expressed as mean ± SEM (n = 16–22 mice per group for body weight, temperature, and blood glucose measurement. N = 6 mice per group for pulse oximetry).

Mentions: Body weight, temperature, blood glucose, and O2 saturation remained comparable at all time points to 28 days after CLP, suggesting a similar physiological response to 5 days of antibiotics versus 3 days (Fig 2). As previously reported, body weight decreases after CLP and then recovers [14], and a stress hyperglycemia occurs in the first week of sepsis [17]. Notably, at 5 days post-CLP, there is no statistical difference between treatment groups in body weight, body temperature, or blood glucose (Table 2).


Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality
Physiological Parameters.There were no physiological differences between mice receiving 5 days of imipenem-cilastatin treatment versus 3 days of treatment following CLP. Data expressed as mean ± SEM (n = 16–22 mice per group for body weight, temperature, and blood glucose measurement. N = 6 mice per group for pulse oximetry).
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Related In: Results  -  Collection

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

pone.0163005.g002: Physiological Parameters.There were no physiological differences between mice receiving 5 days of imipenem-cilastatin treatment versus 3 days of treatment following CLP. Data expressed as mean ± SEM (n = 16–22 mice per group for body weight, temperature, and blood glucose measurement. N = 6 mice per group for pulse oximetry).
Mentions: Body weight, temperature, blood glucose, and O2 saturation remained comparable at all time points to 28 days after CLP, suggesting a similar physiological response to 5 days of antibiotics versus 3 days (Fig 2). As previously reported, body weight decreases after CLP and then recovers [14], and a stress hyperglycemia occurs in the first week of sepsis [17]. Notably, at 5 days post-CLP, there is no statistical difference between treatment groups in body weight, body temperature, or blood glucose (Table 2).

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