UTILIZATION OF TIME-KILL KINETIC METHODOLOGIES FOR ASSESSING THE BACTERICIDAL ACTIVITIES OF AMPICILLIN AND BISMUTH, ALONE AND IN COMBINATION, AGAINST HELICOBACTER-PYLORI IN STATIONARY AND LOGARITHMIC GROWTH PHASES

Assessment of in vitro susceptibility testing of Helicobacter pylori i s difficult because of the fastidious, slowly growing nature of this m icroorganism. The high rate of relapse observed clinically and a possi ble subpopulation of cells that are not actively replicating suggest t he potential need for bactericidal therapy in order to eradicate H. py lori. We used modified time-kill kinetic methodology in order to evalu ate the bactericidal activities of ampicillin and bismuth, alone and i n combination, against three strains of H. pylori in both a stationary (slow) growth phase and a logarithmic (rapid) growth phase. We found that ampicillin produced a decrease in CFU per milliliter (2 to 4 log( 10) units) for three strains of H. pylori when tested in logarithmic g rowth phases but was less inhibitory (<1-log(10)-unit decrease in CFU per milliliter) when tested in a stationary growth phase. In contrast, bismuth, when tested in a logarithmic growth phase, produced little i nhibitory effect, as the CFU for all strains tested increased above th e inoculum. However, when tested in a stationary grow th phase, bismut h produced a decrease in CFU per milliliter of <1 to >3 log(10) units) . The activities of these two agents when combined mimicked the activi ty of the most active drug alone for that growth phase. We conclude th at the clinical use of ampicillin combined with bismuth has been more effective than that of either agent used alone because ampicillin targ ets replicating cells, whereas bismuth targets cells that are not acti vely replicating.