SYNERGY OF T-1982 FOR BACTERICIDAL EFFECT WITH THE COMPLEMENT AND CULTURED MACROPHAGES

Abstract

To clarify the prominentin vivo effect of T-1982, a new parenteral cephem antibiotic, studies were carried out on the synergetic bactericidal and phagocytic effect of the drug with serum complement and cultured mouse macrophages. Other investigations were also performed to see whether or not the drug possesses a direct immuno-potentiating effect to host animals.
10⁵ cells of Escherichia coli NIHJ JC-2 were completely killed within several hours in the presence of T-1982 at the concentration of 50% growth inhibition (ID₅₀) plus 20% human serum and 2% guinea pig complement, each of which showed incomplete bactericidal activity. This effect was found to be most prominent in T-1982 among known cephem antibiotics.
Since T-1982 binds the PBP 3, lb and Ia, cells ofE. coli are converted into filamentous bodies with bulges in the presence of subMIC of the drug. When live cells of E. coil NIHJ JC-2 were added to the mouse cultured macrophages with 1 to 1/2 MIC of T-1982, the filamentous bacterial cells were well phagocytized and digested within 4 hours. Whereas, normal bacterial cells added to the macrophages in the absence of the drug multiplied in the animal cells and destroyed them at 4 hours after incubation.
No immunostimulating effects were confirmed when mice were pretreated with T-1982 and then challenged with Candida parapsilosis or C. albicans. It was suggested that the prominence of in vivo effect of T-1982 depends upon the conversion of bacterial surface as to be easily killed by host defence mechanisms.