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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

Hematologic changes.The shorter 3 day antibiotic treatment did not significantly change peripheral blood measurements in septic mice compared to 5 days of treatment. Five day treatment mice showed elevations of WBC, neutrophil, and lymphocyte counts starting at day 7 which normalized by day 28. Five day treatment had significantly higher WBC and neutrophil counts only at 14 and 21 days post-CLP, respectively. The WBC and neutrophil count remained elevated at day 28 compared to the pre-CLP values, probably due to the ongoing stress of the infection. All other hematologic changes returned to pre-CLP (day 0) levels by day 28. Data expressed as mean ± SEM, n = 16–18 per group, *p < .05 **p < .01.
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pone.0163005.g003: Hematologic changes.The shorter 3 day antibiotic treatment did not significantly change peripheral blood measurements in septic mice compared to 5 days of treatment. Five day treatment mice showed elevations of WBC, neutrophil, and lymphocyte counts starting at day 7 which normalized by day 28. Five day treatment had significantly higher WBC and neutrophil counts only at 14 and 21 days post-CLP, respectively. The WBC and neutrophil count remained elevated at day 28 compared to the pre-CLP values, probably due to the ongoing stress of the infection. All other hematologic changes returned to pre-CLP (day 0) levels by day 28. Data expressed as mean ± SEM, n = 16–18 per group, *p < .05 **p < .01.

Mentions: Following CLP-induced sepsis, there was an initial drop in circulating leukocytes which then rebounded above baseline levels within the first week (Fig 3). The decrease in lymphocytes due to apoptosis [30] also results in the overall decline in the white count and the drop in neutrophils has also been reported following CLP [31]. Minor hematologic changes occurred at discrete time points post-CLP which were probably of little biological relevance. Hemoglobin and platelet levels were not significantly different between the groups up to 28 days post-CLP. Elevated numbers of white blood cells persisted until day 28 and the lymphocyte count remained elevated until day 21. However, the only significant differences by Bonferroni post test were at day 14 for white blood cells and day 21 for neutrophils for 5-day treatment mice (Fig 3). It is possible that the increased neutrophil count reflected a secondary infection in the 5 day treatment regimen, but this is unlikely since there was no change in temperature or body weight typically observed in an infection.


Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality
Hematologic changes.The shorter 3 day antibiotic treatment did not significantly change peripheral blood measurements in septic mice compared to 5 days of treatment. Five day treatment mice showed elevations of WBC, neutrophil, and lymphocyte counts starting at day 7 which normalized by day 28. Five day treatment had significantly higher WBC and neutrophil counts only at 14 and 21 days post-CLP, respectively. The WBC and neutrophil count remained elevated at day 28 compared to the pre-CLP values, probably due to the ongoing stress of the infection. All other hematologic changes returned to pre-CLP (day 0) levels by day 28. Data expressed as mean ± SEM, n = 16–18 per group, *p < .05 **p < .01.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036876&req=5

pone.0163005.g003: Hematologic changes.The shorter 3 day antibiotic treatment did not significantly change peripheral blood measurements in septic mice compared to 5 days of treatment. Five day treatment mice showed elevations of WBC, neutrophil, and lymphocyte counts starting at day 7 which normalized by day 28. Five day treatment had significantly higher WBC and neutrophil counts only at 14 and 21 days post-CLP, respectively. The WBC and neutrophil count remained elevated at day 28 compared to the pre-CLP values, probably due to the ongoing stress of the infection. All other hematologic changes returned to pre-CLP (day 0) levels by day 28. Data expressed as mean ± SEM, n = 16–18 per group, *p < .05 **p < .01.
Mentions: Following CLP-induced sepsis, there was an initial drop in circulating leukocytes which then rebounded above baseline levels within the first week (Fig 3). The decrease in lymphocytes due to apoptosis [30] also results in the overall decline in the white count and the drop in neutrophils has also been reported following CLP [31]. Minor hematologic changes occurred at discrete time points post-CLP which were probably of little biological relevance. Hemoglobin and platelet levels were not significantly different between the groups up to 28 days post-CLP. Elevated numbers of white blood cells persisted until day 28 and the lymphocyte count remained elevated until day 21. However, the only significant differences by Bonferroni post test were at day 14 for white blood cells and day 21 for neutrophils for 5-day treatment mice (Fig 3). It is possible that the increased neutrophil count reflected a secondary infection in the 5 day treatment regimen, but this is unlikely since there was no change in temperature or body weight typically observed in an infection.

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