Prolonged granulocytopenia due to selective antimicrobial modulation of the intestinal flora of irradiated mice: the impact on recovery from infection.

In order to study the effect of modulation of the intestinal flora on granulopoiesis, conventional mice were given drinking water with or without a combination of antimicrobial drugs, i.e. neomycin, polymyxin B, amphotericin B and nalidixic acid. These antimicrobial drugs, which selectively eliminate the aerobic gram-negative rods and suppress yeasts, are currently administered to our patients to prevent infection during granulocytopenia (nalidixic acid has been replaced by pipemidinic acid). After sublethal irradiation, mice on antimicrobial drugs were granulocytopenic longer than the controls. Although these differences were rather small, i.e. two days, the impact on the course of an experimental infection at the end of the period of granulocytopenia was substantial. After injection of 1 x 10(5) live bacteria into the thigh muscle, both groups of granulocytopenic mice exhibited an initial increase in the number of bacteria in the thigh muscle. After 18 h a further increase in the number of bacteria was found for 63% of the mice receiving antimicrobial drugs, whereas the number had dropped below the baseline in 77% of the controls. These differences were reflected in the incidence of bacteremia, i.e. positive blood cultures for the bacteria injected into the thigh muscle were found for 26% of the mice on antimicrobial prophylaxis versus only 2% of the control mice. Remarkably, the number of peripheral blood granulocytes correlated with the number of CFU isolated from the thigh 18 h after injection for the animals on prophylaxis but not for the controls. This might mean that modulation of the intestinal flora affects not only the number of circulating granulocytes, but also other host defense factors.