IMPACT OF BETA-LACTAMASES ON THE CLINICAL USE OF BETA-LACTAM ANTIBIOTICS

beta-Lactamase production is a very common mechanism of antibiotic res istance, occurring in a wide variety of important pathogens involved i n both community-acquired and nosocomial infections. The beta-lactamas es can be divided into four classes (A, B, C, and D), each of which co ntains both chromosomal and plasmid-encoded enzymes. The impact of bet a-lactamases on the clinical use of beta-lactam antibiotics depends on the spectrum of activity of the enzymes, the prevalence of beta-lacta mase production in a given species, the frequency of involvement of th e pathogen in infections, and whether the infection is treated in hosp ital or in the community. The class A and class C beta-lactamases gene rally have the most impact on clinical practice. Plasmid-mediated clas s A enzymes are produced by a wide range of common pathogens; these en zymes are primarily penicillinases such as TEM(1), SHV1 and ROB(1), bu t in addition include extended-spectrum beta-lactamases which can also hydrolyze cephalosporins. The vast majority of the class A enzymes ca n be inhibited by currently-available beta-lactamase inhibitors. The c lass C enzymes or cephalosporinases, production of which is related to the presence of beta-lactam inducers, are present in nosocomial patho gens such as members of the Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. Constitutive hyperproduction of class C enzyme s, resulting from mutations in regulatory genes, leads to third-genera tion cephalosporin resistance in these organisms. To provide the best antimicrobial treatment, and to ensure that beta-lactam antibiotics ar e used to their optimum effect, clinicians need to remain aware of the prevalence of particular beta-lactamases in their areas or institutio ns, and to make use of appropriate counter measures such as beta-lacta m/beta-lactamase inhibitor combinations.