Abstract
Derepression of β-lactamases in certain non-fastidious Gram-negative bacilli has been responsible for (i) the rapid development of resistance to a variety of β-lactam antibiotics and (ii) antagonism between β-lactam antibiotics. Therefore, the effects of a variety of inhibitiors of macromolecular synthesis on derepression of β-lactamase were investigated with four strains each of enterobacter and Pseudomonas aeruginosa. When tested at concentrations that were not inhibitory to growth, clindamycin was the most effect inhibitor of derepression of β-lactamases in some of the strains examined. In one enterobacter isolate, clindamycin completely prevented derepression of β-lactamases. This effect was highly specific as clindamycin did not influence constitutive β-lactamase or derepression of other inducible enzymes in this same strain. These results suggest that clindamycin may selectively inhibit synthesis of β-lactamase under repressor control in some bacteria without affecting synthesis of other proteins or replication. Such selective inhibition may provide a new approach for the enhancement of the antibacterial activity of certain β-lactam antibiotics.