The mechanisms of synergistic effect of antibiotics. A mechanism of synergism, cephaloridine with gentamicin on cephaloridine resistant gram negative bacilli.

Twelve strains out of 75 Gram negative rods, which were isolated at the clinical laboratory in the hospital, were highly resistant to cephaloridine (CER) and relatively sensitive to gentamicin (GM). Nine strains out of the 12 strains revealed synergistic effect when small doses of GM were used together with CER. A mechanism of synergistic effect on Enterobacter cloacae, 1 strain of the 9 strains, was studied through change of beta-lactamase activities. The levels of viable cell count decreased when small doses of GM were added compared with the ones obtained without the addition of GM. Similarly the levels of protein concentration and beta-lactamase activities in the sonicated component of sediment decreased, so did the level of beta-lactamase activities per cell. On the contrary, however, the beta-lactamase activities in the supernatant fluid showed no difference irrespective of the GM. Based upon the above mentioned findings, it is suggested that synergistic effect of CER and GM might be due to inhibition of protein synthesis as well as due to subsequent inhibition of beta-lactamase synthesis. This is compared with the author's previous study, in which the mechanism of synergistic effect of CER and chloramphenicol (CP) was partly due to inhibition of protein synthesis, but mostly due to inhibition of beta-lactamase synthesis.