Relationship between the effect of carbenicillin on the phagocytosis and killing of Proteus mirabilis by polymorphonuclear leukocytes and therapeutic efficacy.

The relationship between the in vitro antibacterial activity of carbenicillin in the presence of leukocytes and the therapeutic efficacy of the antibiotic against experimental infection in animals was investigated. Proteus mirabilis strains 3 and 60 were selected as the test strains. The susceptibility of these strains to carbenicillin was similar in the conventional broth medium, but differed in the presence of rabbit polymorphonuclear leukocytes or defibrinated rabbit blood; the antibiotic-susceptibility of strain 60 increased with blood components, whereas that of strain 3 did not change greatly. Bacterial cells of these strains, which had been treated with carbenicillin at a concentration of 200,ug/ml, were injected intraperitoneally in mice and the viable cells which invaded the blood stream were counted at regular intervals. The results showed that the invasiveness of strain 60 from the peritoneal cavity into the blood stream was more strongly inhibited by carbenicillin-pretreatment than that of strain 3. When rabbits were given a single intramuscular dose of 20 mg carbenicillin/kg body weight immediately after intravenous challenge with strains 3 and 60, strain 60 disappeared from the blood stream more rapidly than strain 3. These results suggest that the in vitro antimicrobial activity of antibiotics should be evaluated not only in conventional medium but in the presence of body fluids such as serum, blood and leukocytes.