More serious infectious morbidity and mortality associated with simultaneous candidemia and coagulase-negative staphylococcal bacteremia in neonates and in vitro adherence studies between Candida albicans and Staphylococcus epidermidis.

BACKGROUND: Candida species and coagulase-negative staphylococci (CoNS) are common etiologies of hospital acquired bloodstream infection in the neonatal intensive care unit (NICU). Sepsis with either organism may result in serious infectious sequelae and along with other staphylococci are the most common causes of abscess formation in preterm infants. This increased incidence of abscess formation may be in part due to adherence factors of both pathogens. METHODS: All cases of concurrent positive blood cultures for both Candida species and CoNS were identified from the microbiology database in NICU patients from January 1998 to December 2000 and analyzed for risk factors and outcomes. In vitro co-aggregation studies between Candida albicans and Staphylococcus epidermidis were also performed. RESULTS: Six premature infants were identified as having concurrent Candida and CoNS bloodstream infections during this time period. Four of the six patients developed end-organ dissemination with abscess or infected thrombus formation. Three of the six patients expired during or after their infection. In vitro, co-aggregation studies did not demonstrate reproducible direct adherence between C. albicans and S. epidermidis. CONCLUSIONS: Simultaneous bloodstream infection with Candida and CoNS, compared to either one alone, is more likely to predispose to abscess formation, septic thrombophlebitis and mortality. Further studies are needed to examine the pathogenesis of these complex infections.

Costimulation with interleukin-4 and interleukin-10 induces mast cell apoptosis and cell-cycle arrest: the role of p53 and the mitochondrion.

OBJECTIVE: The aim of this study was to determine the mechanism by which interleukin (IL)-4 + IL-10 costimulation regulates mast cell numbers to maintain immune homeostasis. MATERIALS AND METHODS: We employed mouse bone marrow-derived mast cells (BMMC) to measure the effects of IL-4 + IL-10 on survival and cell-cycle progression. p53-Deficient, bax-deficient, and bcl-2 transgenic BMMC were compared to wild-type cells to determine the role of these proteins in apoptosis. The molecular regulation of apoptosis and cell-cycle progression was investigated using flow cytometric analysis, RNase protection, and Western blotting. RESULTS: IL-4 + IL-10 induced BMMC apoptosis and arrest. Apoptosis was p53-dependent. Cell death was accompanied by loss of mitochondrial membrane potential, the importance of which was demonstrated by resistance to IL-4 + IL-10-mediated cell death when Bax was deleted or Bcl-2 was overexpressed. Those cells not killed by apoptosis demonstrated a p53-independent G1 cell-cycle arrest. Apoptosis and arrest may be explained by reduced IL-3 receptor signaling. CONCLUSION: Costimulation with IL-4 + IL-10 partly controls mast cell homeostasis through a delayed apoptosis and arrest program that is induced by a blockade of IL-3 receptor signaling. The delay in these negative effects would allow the protective effects of mast cell activation to occur for several days.