beta-Lactam resistance amongst Enterobacter species.

Following the introduction of extended-spectrum cephalosporins into clinical use, the prevalence of species belonging to the genus Enterobacter has increased because of their natural resistance to earlier cephalosporins and their ability to develop resistance rapidly to the newer drugs. beta-Lactam resistance in this genus is due, for the most part, to the presence of a Bush group 1 chromosomal cephalosporinase. This enzyme is normally inducible and resistance to older cephalosporins, cephamycins and aminopenicillins results from either the extreme lability of the drugs to the enzyme or from their inducer activities. Resistance to newer penicillins, cephalosporins and monobactams is attributable to the selection of mutants which express large amounts of the enzyme. Such mutants arise as the result of a spontaneous mutation in one of the regulatory genes responsible for suppressing enzyme expression. Since the enzyme has very high affinity for the newer cephalosporins, this, coupled with the slow penetration of the drugs into the cell, provides a very efficient mechanism of resistance. Recent surveys in the USA and elsewhere have shown that the increased prevalence of multi-beta-lactam-resistant strains of enterobacter is due to the increased use of the newer cephalosporins. Attempts to prevent these problems include the more judicious use of newer beta-lactam antibiotics and the development of enhanced-potency cephalosporins which are able to avoid resistance because they have lower enzyme affinity and permeate more rapidly into the cell.