Mortality and bacteriology of sepsis following cecal ligation and puncture in aged mice

Abstract

Epidemiologic data suggest that elderly adults are more susceptible to invasive bacterial infection by indigenous gut flora than are younger adults. The purpose of this investigation was to characterize a murine model of clinically encountered peritonitis in the aged. We subjected three different age groups (young, 16 weeks; mature, 12 months; senescent, 24 months) of C57BL/6NNia mice to surgically induced peritonitis by the cecal ligation and puncture procedure. Senescent mice died in a significantly shorter time following surgery than mature mice (median time to death, 24.4 versus 38.5 h, respectively; P less than or equal to 0.001). Blood, liver, spleen and occasionally, ceca were obtained at 2 and 12 h after the cecal ligation and puncture procedure and immediately following death, to characterize the bacterial kinetics of the model. Qualitative and quantitative aerobic, anaerobic, and coliform cultures were performed. No age-related differences were found in the types of bacteria isolated throughout the time course of progressive sepsis. In mice in the mature and senescent age groups, at 2 and 12 h postsurgery, gram-negative anaerobes and gram-positive aerobes predominated in all tissues that were cultured. At the time of death, however, blood and tissue isolates consisted predominantly of coliform bacteria. The shift from mixed infection during sepsis to predominantly gram-negative bacterial infection reflected a similar progressive shift in bacterial types found in the cecum. At death, senescent mice had 100-fold fewer coliform bacteria in the bloodstream than those found in mature mice (2.5 x 10(9) versus 4.6 x 10(11), respectively). The increased sensitivity of aged mice to invasive bacterial infection documented in this series of experiments accords well with human epidemiologic experience and demonstrates the appropriateness of the model for continued investigations of sepsis in the aged.