Activity of amikacin and ampicillin in succession and in combination

One strain each of Escherichia coli and Streptococcus faecalis were exposed to amikacin and ampicillin in combination as well as in succession. Exposure to ampicillin for 1 hr followed by amikacin for 3 or 4 hr had the greatest antibacterial activity when the antibiotics were applied in succession. The least effective exposures for both organisms were 1 hr to amikacin followed by 3 or 4 hr to ampicillin. Exposure to the antibiotics in combination each at 1 MIC had the overall greatest antibacterial activity. Simultaneous exposure to the antibiotic combination does not necessarily mean simultaneous activity of both ampicillin and amikacin on the E. coli. The cell wall autolytic activities produced by ampicillin are triggered within 10 min after physical contact with the bacteria. In contrast, amikacin requires at least 30 min after physical contact to manifest its activity on the ribosome. Although physical exposure to both antibiotics in the combination is simultaneous, the specific activity of each is in fact sequential, with ampicillin acting first. This explains the synergistic effect of the combination. It appears, therefore, that the synergistic or antagonistic affect of a drug combination is determined by the sequence and timing of the antibacterial manifestations of its components.