The Rate of Killing of Escherichia coli by -Lactam Antibiotics Is Strictly Proportional to the Rate of Bacterial Growth

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Abstract
Nongrowing bacteria evade the bactericidal activity of .beta.-lactam antibiotics. We sought to determine if slow growth rate also alters bactericidal activity. The bactericidal activity of two .beta.-lactams on Escherichia coli grown in glucose limited chemostats was compared for generation times ranging from 0.7 to 12 h. The degree of killing varied with drug structure and with E. coli strains. However, all killing rates were a constant function of the bacterial generation time: slowly growing bacteria became progressively more phenotypically tolerant to .beta.-lactam antibiotics as the generation time was extended.