Nosocomial bacteremia-induced increases in abscess formation correlate with in vitro upregulation of macrophage procoagulant activity.

Abstract

To evaluate the hypothesis that sublethal exposure to common nosocomial pathogens can alter the host response to a later, distant infectious insult (peritonitis and intraperitoneal abscess formation), and that these changes are related to the induction of macrophage procoagulant activity. A multiexperiment, randomized, controlled trial. Animal research laboratory of a university medical center. One hundred sixty-five Balb/c mice, weighing 20 to 25 g, were used for in vivo experiments and as the source of peritoneal macrophages for in vitro experiments. Nine groups of mice (n = 10 to 18 per group) were twice systemically preexposed to sublethal amounts of live Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, Staphylococcus epidermidis, Enterococcus faecalis, or Candida albicans, or to 2.5 or 5.0 micrograms E. coli lipopolysaccharide O26:B6. One week later, mice underwent the induction of mixed E. coli/Bacteroides fragilis peritonitis, leading to abscess formation. In parallel experiments in vitro, 10(6) mouse peritoneal macrophages were incubated with similar amounts of nosocomial pathogens or lipopolysaccharide to determine the induction of macrophage procoagulant activity. The three Gram-negative bacilli tested significantly upregulated both abscess formation and macrophage procoagulant activity, with a strong linear correlation between abscess formation and procoagulant activity. These effects were not seen with the Gram-positive cocci or with C. albicans. Pre-exposure of mice to endotoxin alone did not alter later abscess formation, but did increase macrophage procoagulant activity. Sublethal exposure to some Gram-negative nosocomial pathogens can significantly alter a host's response to a later, distant, infection, even when caused by different bacteria. In the case of peritonitis and intraperitoneal abscess formation, these changes may be mediated by the upregulation of macrophage procoagulant activity. The presence of endotoxin alone does not completely explain these phenomena.