ABSTRACT
The effect of hyperglycemia upon susceptibility to bacterial infection in diabetes mellitus is incompletely elucidated. The present experiments assessed the effect of hyperglycemia upon neutrophil-mediated phagocytosis of type III group B Streptococcus (GBS). Type III GBS was chosen for study because the incidence of invasive GBS disease is substantially increased in type 2 diabetic compared with nondiabetic subjects. The hypothesis tested was that severe hyperglycemia would alter neutrophil metabolism by diverting NADPH from superoxide production into the aldose reductase-dependent polyol pathway that converts glucose into sorbitol and thus would impair opsonophagocytosis (OP) of type III GBS. Neutrophils from 10 adults with type 2 diabetes had no intrinsic phagocytic defect under baseline glycemic conditions. After equilibration in 60 or 120 mM glucose or in 60 mM choline chloride, OP activity was reduced significantly (P < or = 0.03). Neutrophil superoxide production correlated with glucose concentration and also was significantly reduced during hyperglycemia (P < 0.05). Addition of III GBS capsular polysaccharide-specific IgG in a sufficient concentration supported efficient OP, even during hyperglycemia. Alrestatin, an aldose reductase inhibitor, increased superoxide production and significantly improved OP of type III GBS (P = 0.03). Thus, diversion of NADPH into the polyol pathway is one mechanism by which OP of GBS III is impaired during hyperglycemia, and this effect is mitigated when levels of capsular polysaccharide-specific IgG are sufficient.
Subject(s)
Diabetes Mellitus, Type 2/metabolism , Neutrophils/metabolism , Streptococcus agalactiae/metabolism , Superoxides/metabolism , Adult , Aged , Aldehyde Reductase/antagonists & inhibitors , Blood Glucose/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Female , Humans , Hyperglycemia/metabolism , Immunoglobulin G/metabolism , Isoquinolines/pharmacology , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Phagocytosis , Time FactorsABSTRACT
We report an infant with congenital tuberculosis who presented with fulminant septic shock, disseminated intravascular coagulation and respiratory failure. Aggressive resuscitation and supportive care and prompt initiation of antituberculosis medications led to resolution of the shock state. We reviewed six other cases with a similar presentation. Congenital tuberculosis should be in the differential of the infant presenting acutely with sepsis syndrome.