Impact of beta-lactamases on the clinical use of beta-lactam antibiotics.
beta-Lactamase production is a very common mechanism of antibiotic resistance, occurring in a wide variety of important pathogens involved in both community-acquired and nosocomial infections. The beta-lactamases can be divided into four classes (A, B, C, and D), each of which contains both chromosomal and plasmid-encoded enzymes. The impact of beta-lactamases on the clinical use of beta-lactam antibiotics depends on the spectrum of activity of the enzymes, the prevalence of beta-lactamase production in a given species, the frequency of involvement of the pathogen in infections, and whether the infection is treated in hospital or in the community. The class A and class C beta-lactamases generally have the most impact on clinical practice. Plasmid-mediated class A enzymes are produced by a wide range of common pathogens; these enzymes are primarily penicillinases such as TEM(1), SHV(1) and ROB(1), but in addition include extended-spectrum beta-lactamases which can also hydrolyze cephalosporins. The vast majority of the class A enzymes can be inhibited by currently-available beta-lactamase inhibitors. The class C enzymes or cephalosporinases, production of which is related to the presence of beta-lactam inducers, are present in nosocomial pathogens such as members of the Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. Constitutive hyperproduction of class C enzymes, resulting from mutations in regulatory genes, leads to third-generation cephalosporin resistance in these organisms. To provide the best antimicrobial treatment, and to ensure that beta-lactam antibiotics are used to their optimum effect, clinicians need to remain aware of the prevalence of particular beta-lactamases in their areas or institutions, and to make use of appropriate counter measures such as beta- lactam beta- lactamase inhibitor combinations.
Nicolas-Chanoine
M H
MH
Service Microbiologie et Hygiène, Hôpital Ambroise Paré, 9 Avenue Charles de Gaulle, 92104 Boulogne Cedex, France.