ENHANCED CLEARANCE OF A MULTIPLE ANTIBIOTIC-RESISTANT STAPHYLOCOCCUS-AUREUS IN RATS TREATED WITH PGG-GLUCAN IS ASSOCIATED WITH INCREASED LEUKOCYTE COUNTS AND INCREASED NEUTROPHIL OXIDATIVE BURST ACTIVITY

PGG-Glucan [Betafectin(R)], a highly purified soluble beta-(1-6)-branc hed beta-(1-3)-linked glucan isolated from Saccharomyces cerevisiae, h as broad in vitro and in vivo anti-infective activities unrelated to c ytokine induction. Here we present in vivo results on the anti-infecti ve activity of PGG-Glucan against a multiple antibiotic resistant Stap hylococcus aureus. PGG-Glucan (0.25-4 mg/kg) was administered intramus cularly to male Wistar rats 48 h, 24 h, and 4 h before and 4 h after i ntraperitoneal implantation of a gelatin capsule containing 10(8) S. a ureus colony forming units (CFU). Blood samples were collected at vari ous times after challenge to determine CFU levels, leukocyte counts an d neutrophil oxidative burst activity; serum TNF-alpha and IL-1 beta l evels were also evaluated. The 0.25 mg/kg PGG-Glucan dose had no effec t on reducing blood CFU levels; however, PGG-Glucan doses of 0.5 mg/kg , 1 mg/kg, 2 mg/kg or 4 mg/kg significantly reduced blood CFU levels b y 48 h after challenge. Reduced CFU levels correlated with significant ly elevated absolute monocyte counts, absolute neutrophil counts, and neutrophil oxidative burst activity in the absence of any effect on TN F-alpha or on IL-1 beta levels. In additional studies, effects on mort ality and blood CFU levels were evaluated in rats treated with ampicil lin (an antibiotic to which the S. aureus was resistant), PGG-Glucan, or both agents. Mortality and blood CFU levels were reduced most in co mbination-treated rats compared to saline control rats or rats treated with either ampicillin alone or PGG-Glucan alone. We conclude that in vivo (1) PGG-Glucan can enhance clearance of an antibiotic resistant S. aureus, (2) that this clearance is accompanied by an increase in mo nocytes and neutrophils as well as a potentiation of neutrophil oxidat ive microbiocidal activity without alteration of the proinflammatory c ytokine response, and (3) PGG-Glucan can enhance the effectiveness of traditional antibiotic treatment. (C) 1998 International Society for I mmunopharmacology. Published by Elsevier Science Ltd.