title: 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 beta-(1-6)-branched beta-(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-alpha, and IL-1beta 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-alpha or on IL-1beta 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.
authors.affiliation: Alpha-Beta Technology, Inc., Worcester, MA 10605, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liang
authors.forename: D
authors.initials: D
authors.lastname: Melican
authors.forename: L
authors.initials: L
authors.lastname: Cafro
authors.forename: G
authors.initials: G
authors.lastname: Palace
authors.forename: L
authors.initials: L
authors.lastname: Fisette
authors.forename: R
authors.initials: R
authors.lastname: Armstrong
authors.forename: M L
authors.initials: ML
authors.lastname: Patchen
mesh_terms: D000042:Absorption; D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D005936:Glucans / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006207:Half-Life; D007958:Leukocyte Count / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010406:Penicillins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016897:Respiratory Burst / Q000187:drug effects*; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D013211:Staphylococcus aureus; D047071:beta-Glucans
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D005936:Glucans; D010406:Penicillins; D047071:beta-Glucans; C069894:poly-1-6-glucopyranosyl-1-3-glucopyranose glucan; D000667:Ampicillin