Increased phagocytosis and killing of Escherichia coli treated with subinhibitory concentrations of cefamandole and gentamicin in isolated rat livers

Abstract

Our purpose was to study whether treatment of Escherichia coli with subinhibitory concentrations of either cefamandole or gentamicin could change bacterial susceptibility to the serum bactericidal effect and to the phagocytic and killing activity of the rat liver reticuloendothelial system. Bacteria were grown overnight with 1/5 or 1/10 of the MIC of each antibiotic. At one-fifth of the MIC, cefamandole induced filamentous elongated bacteria whose viability was decreased by 75%. The susceptibility of control and antibiotic-treated bacteria to serum was tested by measuring the survival of organisms exposed to different concentrations of rat serum in vitro. Susceptibility of bacteria to hepatic macrophage activity was tested by following the hepatic clearance of bacteria after they were added to the perfusate of the isolated rat liver. E. coli treated with subinhibitory concentrations of cefamandole or gentamicin appeared somewhat more resistant to the lytic activity of serum at a concentration of 4%, but not at 20%. Bacteria treated with 1/5 or 1/10 of the MIC of cefamandole or with 1/5 of the MIC of gentamicin were significantly more susceptible to phagocytosis and to the bactericidal activity of liver macrophages. Cefamandole appeared more potent than gentamicin in inducing these effects. The results suggest that subinhibitory levels of antibiotics may alter bacterial cell surface (cefamandole) or may impair the expression of antiphagocytic material (gentamicin), thus favoring phagocytosis and killing by macrophages. Our study provides evidence that antibiotics at subinhibitory concentrations may cooperate with host defence mechanisms against bacterial infections.