The effects of therapeutic concentrations of ampicillin on non-beta-lactamase and beta-lactamase producing strains of Neisseria gonorrhoeae were studied. A small but significant fraction of bacteria in a gonococcal population was found to respond in a bacteriostatic rather than a bactericidal way upon ampicillin treatment. In agreement with this was the finding of morphologically unaltered cells in the scanning electron microscope after ampicillin exposure. Ampicillin treatment of beta-lactamase producing gonococci caused a significant release of the enzyme into the surrounding growth media. However, initially all beta-lactamase activity was cellbound. The rate of initial ampicillin hydrolysis was much higher in intact cells of N. gonorrhoeae (TEM-1) than in cells of Escherichia coli K-12 (TEM-1). This suggests that the diffusion rate of ampicillin is much higher in the former organism. The viability of gonococci (TEM-1) was unlike E. coli (TEM-1) affected by low concentrations of ampicillin. However, after complete hydrolysis of ampicillin, viable gonococci (probably bacteriostatic reacting cells) were able to initiate new growth. This heterogeneity of the cell population to penicillin killing is probably one reason why beta-lactamase producing gonococci despite a rather low MIC-value to ampicillin cause infections that are not susceptible to therapy by this agent.
Ampicillin Escherichia coli