Antibiotics delay but do not prevent bacteremia and lung injury in murine sepsis

Abstract

Objectives: To investigate the effect of antibiotics on infection, lung injury, and mortality rate in polymicrobial sepsis and to determine whether an association exists between infection and lung injury and mortality rate. To circumvent the effect of antibiotics on cultures, we used polymerase chain reaction to detect bacteria. Design: Prospective, randomized, controlled laboratory trial. Setting: University research laboratory. Subjects: C57/BL6 mice. Interventions: Mice underwent cecal ligation and puncture without antibiotics (CLP) or with imipenem (CLP + Abx). Measurements and Main Results: CLP resulted in 50% mortality rate at 48 hrs and 100% mortality rate at 84 hrs. Antibiotics delayed these time points to 72 and 120 hrs, respectively. Lung injury occurred before mortality in both groups. Polymerase chain reaction detected bacteria in the blood and lungs of all CLP mice by 24 hrs. Antibiotics delayed but did not prevent infection in CLP + Abx mice. Serum tumor necrosis factor-α and lung endotoxin were elevated to similar concentrations in both CLP and CLP + Abx mice. Conclusions: In this model of sepsis, antibiotics delay but do not prevent acute lung injury and mortality. Even in the presence of antibiotics, acute lung injury is strongly associated with bacteremia and bacteria within the lungs.