effect of antibiotics on LPS release from salmonella typhi and its relation to TNF-a production by human whole blood, EX-VIVO

ABSTRACT

It seems that rapid destruction of gram negative bacteria by antibiotics contributes to the clinical deterioration of some patients with gram negative infections. Antibiotics increase the concentration of lipopolysaccharide [LPS] in blood and cerebrospinal fluids. Released LPS can activate blood cells to produce tumor necrosis factor-alpha [TNF-alpha] and other cytokines. TNF-[alpha] appears to be a major mediator in development of fever, hypotension, multi-organ failure and death. In this research, standard Salmonella typhi Ty[2] -5536, a pathogenic Salmonella and standard Escherichia coli K12,QD5003 for comparing, were incubated in the presence of chloramphenicol, ampicillin and co-trimoxazole at concentrations that killed >99.9% of organisms as determined by quantitative culture techniques. The results obtained showed that chloramphenicol produced lower LPS levels and lower TNF-[alpha] levels from whole blood cells when compared with those of ampicillin and co-trimoxazole. Therefore chloramphenicol is the preferred antibiotic against S. typhi because it decreases the induced-pathological effect of TNF-[alpha] in gram negative infections