Induction of beta-lactamase in Gram-negative bacteria

The induction of beta-lactamase in Gram-negative bacteria in vitro has been established. It is possible to distinguish between high and low beta-lactamase inducers in vitro. This differentiation is clinically irrelevant because induction has little effect on the treatment of a bacterial infection with beta-lactam antibiotics. Regardless of the amount of induced beta-lactamase, the kill kinetics are usually not affected. In mutated cells, the regulatory mechanism is destroyed by inactivation of the relevant genes with respect to their regulatory function, particularly by inactivation of the amp D gene. These mutants overproduce the beta-lactamase constitutively, which results in an enzyme level that significantly exceeds the induced level. The induction process is probably not the cause of clinical failures associated with the use of beta-lactam antibiotics. It is concluded that the selection of resistant mutants with constitutive overproduction of beta-lactamase is the reason for most of these treatment failures.