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

Abstract

PGG-Glucan [Betafectin ®], a highly purified soluble β-(1–6)-branched β-(1–3)-linked glucan isolated from Saccharomyces cerevisiae, has broad in vitro and in vivo anti-infective activities unrelated to cytokine induction. Here we present in vivo results on the anti-infective activity of PGG-Glucan against a multiple antibiotic resistant Staphylococcus aureus. PGG-Glucan (0.25–4 mg⧹kg) was administered intramuscularly to male Wistar rats 48 h, 24 h, and 4 h before and 4 h after intraperitoneal implantation of a gelatin capsule containing 10 8 S. aureus colony forming units (CFU). Blood samples were collected at various times after challenge to determine CFU levels, leukocyte counts and neutrophil oxidative burst activity; serum TNF- α and IL-1 β levels were also evaluated. The 0.25 mg⧹kg PGG-Glucan dose had no effect 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 by 48 h after challenge. Reduced CFU levels correlated with significantly elevated absolute monocyte counts, absolute neutrophil counts, and neutrophil oxidative burst activity in the absence of any effect on TNF- α or on IL-1 β levels. In additional studies, effects on mortality and blood CFU levels were evaluated in rats treated with ampicillin (an antibiotic to which the S. aureus was resistant), PGG-Glucan, or both agents. Mortality and blood CFU levels were reduced most in combination-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 monocytes and neutrophils as well as a potentiation of neutrophil oxidative microbiocidal activity without alteration of the proinflammatory cytokine response, and (3) PGG-Glucan can enhance the effectiveness of traditional antibiotic treatment.