NOSOCOMIAL BACTEREMIA-INDUCED INCREASES IN ABSCESS FORMATION CORRELATE WITH IN-VITRO UP-REGULATION OF MACROPHAGE PROCOAGULANT ACTIVITY

Objective: To evaluate the hypothesis that sublethal exposure to commo n 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 pr ocoagulant activity. Design: A multiexperiment, randomized, controlled trial. Setting: Animal research laboratory of a university medical ce nter. Subjects: One hundred sixty-five Balb/c mice, weighing 20 to 25 g, were used for in vivo experiments and as the source of peritoneal m acrophages for in vitro experiments. Interventions: Nine groups of mic e (n = 10 to 18 per group) were twice systemically preexposed to suble thal amounts of live Escherichia coli, Enterobacter cloacae, Pseudomon as aeruginosa, Staphylococcus epidermidis, Enterococcus faecalis, or C andida albicans, or to 2.5 or 5.0 mu g E. coli lipopolysaccharide O26: B6. One week later, mice underwent the induction of mixed E. coli/Bact eroides fragilis peritonitis, leading to abscess formation. In paralle l experiments in vitro, 10(6) mouse peritoneal macrophages were incuba ted with similar amounts of nosocomial pathogens or lipopolysaccharide to determine the induction of macrophage procoagulant activity. Measu rements and Main Results: The three Gram-negative bacilli tested signi ficantly upregulated both abscess formation and macrophage procoagulan t 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 macropha ge procoagulant activity. Conclusions: Sublethal exposure to some gram -negative nosocomial pathogens can significantly alter a host's respon se to a later, distant, infection, even when caused by different bacte ria. In the case of peritonitis and intraperitoneal abscess formation, these changes may be mediated by the upregulation of macrophage proco agulant activity. The presence of endotoxin alone does not completely explain these phenomena.