Induction of Experimental Endocarditis by Continuous Low-Grade Bacteremia Mimicking Spontaneous Bacteremia in Humans

Abstract

ABSTRACTTransient high-grade bacteremia following invasive procedures carries a risk of infective endocarditis (IE). This is supported by experimental endocarditis. On the other hand, case-control studies showed that IE could be caused by cumulative exposure to low-grade bacteremia occurring during daily activities. However, no experimental demonstration of this latter possibility exists. This study investigated the infectivity in animals of continuous low-grade bacteremia compared to that of brief high-grade bacteremia. Rats with aortic vegetations were inoculated withStreptococcus intermedius,Streptococcus gordoniiorStaphylococcus aureus(strains Newman and P8). Animals were challenged with 103to 106CFU. Identical bacterial numbers were given by bolus (1 ml in 1 min) or continuous infusion (0.0017 ml/min over 10 h). Bacteremia was 50 to 1,000 times greater after bolus than during continuous inoculation. Streptococcal bolus inoculation of 105CFU infected 63 to 100% vegetations compared to 30 to 71% infection after continuous infusion (P> 0.05). When increasing the inoculum to 106CFU, bolus inoculation infected 100% vegetations and continuous infusion 70 to 100% (P> 0.05).S. aureusbolus injection of 103CFU infected 46 to 57% valves. This was similar to the 53 to 57% infection rates produced by continuous infusion (P> 0.05). Inoculation of 104CFU ofS. aureusinfected 80 to 100% vegetations after bolus and 60 to 75% after continuous infusion (P> 0.05). These results show that high-level bacteremia is not required to induce experimental endocarditis and support the hypothesis that cumulative exposure to low-grade bacteremia represents a genuine risk of IE in humans.