picibanil and Bacteremia

OK-432 has been used clinically as a biological response modifier for cancer therapy. We investigated here the protective effects of OK-432 against endotoxic shock and infectious death caused by Pseudomonas aeruginosa and Salmonella enteritidis in mice and proposed a possible mechanism. Pretreatment of OK-432 reduced the lethality of lipopolysaccharide (LPS)-induced endotoxic shock in D-(+)-galactosamine-sensitized C3H/HeN mice. OK-432 did not affect the TNFalpha production in blood, but it did decrease the susceptibility to TNFalpha. Furthermore, an acceleration of LPS clearance from blood was detected. The pretreatment of OK-432 also decreased the lethality of mice in bacterial infection caused by P. aeruginosa and S. enteritidis. The rapid decrease of the viable bacteria from the circulating blood and in spleen and liver in mice was observed in a manner similar to LPS clearance. These findings indicate that the protective effect of OK-432 against the endotoxemia and bacteremia may depend on an up-regulation of clearance of LPS and bacteria and the augmented resistance to TNFalpha.

Topics: Animals; Bacteremia; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Immunologic; Endotoxemia; Female; Lipopolysaccharides; Male; Mice; Mice, Inbred C3H; Picibanil; Pseudomonas aeruginosa; Pseudomonas Infections; Salmonella enteritidis; Salmonella Infections; Shock, Septic; Tumor Necrosis Factor-alpha

The effects of combined treatment with OK-432, an immunomodulator prepared from Streptococcus haemolyticus, and aztreonam, a monobactum antibiotic, in the prevention of radiation-induced bacteraemia and mortality were examined in ICR-MCH mice irradiated with 9.5 Gy. The organisms recovered from the irradiated mice were Streptococcus faecalis and Proteus mirabilis. Treatment with aztreonam reduced the incidence of mice infected with Proteus mirabilis (p < 0.01), but it showed no efficacy on Streptococcus faecalis. OK-432 could reduce the frequency of bacteraemia attributed to both organisms (p < 0.05). Combined treatment with OK-432 and aztreonam further decreased the incidence of bacteraemia by both organisms; no organisms were recovered at 14 days following irradiation. The survival rate at 30 days following irradiation was 80% in mice treated with OK-432 plus aztreonam and 55% with OK-432 alone, while it was 0% in the groups treated with aztreonam or saline alone. These results indicated that combined treatment with OK-432 and a suitable antibiotic such as aztreonam is more effective than OK-432 or aztreonam alone.

Topics: Animals; Aztreonam; Bacteremia; Enterococcus faecalis; Mice; Picibanil; Proteus mirabilis; Radiation Injuries, Experimental; Radiation-Protective Agents; Specific Pathogen-Free Organisms; Time Factors