Combined action of decreasing concentrations of azlocillin and sisomicin on Pseudomonas aeruginosa as assessed in a dynamic in vitro model.

The effect of decreasing concentrations of azlocillin and sisomicin on Pseudomonas aeruginosa was examined. Logarithmically growing bacterial cultures were incubated in an ultrafiltration cell, and after adding the antibiotics, the culture medium was diluted every 20 min without any decrease in cell density. The turn-over of medium resulted in the elimination of azlocillin with a half-life of 75 min. This simulated serum kinetics in vivo. When testing sisomicin, small amounts of this agent were added during every dilution step to achieve a half-life of 120 min. Growth conditions were comparable in all experiments. The simultaneous combination of azlocillin and sisomicin resulted in strong synergism as assessed by higher killing rates and more prolonged growth inhibition of surviving bacteria. Comparable results were observed when both drugs were added at intervals of 40 min. When applied at intervals of 120 min, the combined effect of azlocillin and sisomicin was reduced, but still superior to the effect of double the concentration of each compound alone. Thus, neither pre-treatment with azlocillin nor with sisomicin impaired the antibacterial activity of the combination partner. This seems to be of clinical importance since the agents may be administered at different times during combined therapy.