β-Lactam coselection of sensitive and TEM-1 β-lactamase-producing subpopulations in heterogeneous Escherichia coli colonies

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Abstract
We tested the effect of different concentrations of cefamandole, cefotaxime, cefoxitin and imipenem on homogeneous and heterogeneous bacterial stationary colonies. A reduction of not more than 100-fold in the bacterial colony population was obtained with sensitive Escherichia coli K12 strains. When an E. coli strain producing high levels of TEM-1 β-lactamase constituted 6% or more of the population, the whole colony was resistant to cefamandole, but still sensitive to cefotaxime, cefoxitin or imipenem. Thus in the case of cefamandole the sensitive subpopulation is co-selected by the resistant one. It is suggested that the occurrence of resistant subpopulations, as a small part of an apparently sensitive E. coli population, can lead to therapeutic failures with β-lactamase-sensitive agents.