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A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
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Antibiotic treatment influences outcome in murine sepsis: mediators of increased morbidity

D Newcomb1, G Bolgos, L Green

  • 1Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.

Shock (Augusta, Ga.)
|August 29, 1998
PubMed

Insights

The broad-spectrum antibiotic imipenem (IMP) improved survival in mice after cecal ligation and puncture (CLP) compared to a triple antibiotic mixture (3AB). The 3AB treatment caused hypothermia and increased mortality, but not via elevated cytokines or lipopolysaccharide (LPS).

Area of Science:

  • Microbiology and Immunology
  • Pharmacology and Therapeutics
  • Sepsis and Critical Care Research

Background:

  • Antibiotic selection critically influences patient outcomes in sepsis.
  • The cecal ligation and puncture (CLP) model is a standard method for inducing polymicrobial sepsis in rodents.
  • Understanding antibiotic-specific physiological effects is crucial for optimizing sepsis treatment.

Purpose of the Study:

  • To compare the efficacy and physiological impact of imipenem (IMP) versus a triple antibiotic mixture (3AB) in a murine CLP model.
  • To investigate the mechanisms behind observed differences in survival and physiological responses, including temperature and activity.
  • To assess the role of cytokines and lipopolysaccharide (LPS) in mediating antibiotic-induced effects.

Main Methods:

  • Balb/c mice underwent CLP surgery.
  • Mice received either IMP, 3AB (gentamicin, clindamycin, ciprofloxacin), or dextrose (D5W) intravenously post-CLP.
  • Temperature and activity were monitored using Mini-Mitters; plasma and peritoneal cytokines (IL-1, IL-6, TNF, KC) and LPS were measured at specific time points.

Main Results:

  • Survival rates were significantly higher in the IMP group compared to the 3AB and D5W groups.
  • The 3AB treatment induced profound hypothermia and reduced nocturnal activity, effects not seen with IMP or D5W.
  • No significant differences in cytokine or LPS levels were found between the antibiotic treatment groups.

Conclusions:

  • Imipenem (IMP) demonstrates superior outcomes in a murine sepsis model compared to a triple antibiotic regimen (3AB).
  • The triple antibiotic mixture (3AB) is associated with increased morbidity and mortality, potentially due to hypothermia and reduced activity.
  • The detrimental effects of 3AB are not attributable to elevated systemic cytokine or LPS concentrations.

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