Effects of clindamycin on derepression of beta-lactamases in gram-negative bacteria

Depression of beta-lactamases in certain non-fastidious Gram-negative bacilli has been responsible for (i) the rapid development of resistance to a variety of beta-lactam antibiotics and (ii) antagonism between beta-lactam antibiotics. Therefore, the effects of a variety of inhibitors of macro-molecular synthesis on derepression of beta-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 effective inhibitor of derepression of beta-lactamases in some of the strains examined. In one enterobacter isolate, clindamycin completely prevented derepression of beta-lactamases. This effect was highly specific as clindamycin did not influence constitutive beta-lactamase or depression of other inducible enzymes in this same strain. These results suggest that clindamycin may selectively inhibit synthesis of beta-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 beta-lactam antibiotics.