Clinical Significance and Pathogenesis of Hyperbilirubinemia Associated with Staphylococcus aureus Septicemia

Abstract

Our goal was to examine the clinical significance of hyperbilirubinemia in patients with Staphylococcus aureus endocarditis. In addition, preliminary data concerning the possible mechanism of cholestasis observed during S. aureus septicemia are presented. This study had two parts: a clinical investigation and a laboratory investigation. In the former, patients with endocarditis were identified through chart review. Those with admission total serum bilirubin levels of 2.0 mg/dl or greater were considered to have hyperbilirubinemia. In the latter investigation, the hepatic storage capacity and transport maximum for sulfobromophthalein (BSP), an organic dye that is rapidly taken up and excreted by the liver, were determined by measuring the change in serum concentration and the corresponding hepatic removal rate at various BSP infusion rates. Measurements were conducted before and after the infusion of Escherichia coli-derived lipopolysaccharide in some rabbits, after the infusion of resuspended S. aureus in others, and after the infusion of lipoteichoic acid in the remainder. Eleven of 47 consecutive patients with S. aureus endocarditis were noted to have hyperbilirubinemia without clinical or laboratory evidence of hepatic bacterial infection. Compared with the remaining 36 patients, these 11 patients had a significantly lower mean platelet count and a higher serum creatinine level and white blood cell count. Although none of the 47 patients were hypotensive on admission, four of the 11 hyperbilirubinemic patients died of overwhelming sepsis, compared with two of the 36 remaining patients (p less than 0.05). When one of the clinical isolates of S. aureus or lipoteichoic acid was infused into conscious rabbits, there was a marked decrease in the hepatic transport maximum and an increase in the relative hepatic storage capacity of sulfobromophthalein. Similar changes were noted following the administration of lipopolysaccharide. Our data suggest that the presence of hyperbilirubinemia in patients with S. aureus sepsis may identify persons at high risk of dying from overwhelming sepsis. It further suggests that lipoteichoic acid may play an important role in causing defective hepatic excretory function that is responsible for hyperbilirubinemia.