IMPORTANT AND EMERGING BETA-LACTAMASE-MEDIATED RESISTANCES IN HOSPITAL-BASED PATHOGENS - THE AMP-C ENZYMES

Resistance to third-generation cephalosporins mediated by beta-lactama ses is an increasing problem for clinical therapeutics. A wide range o f Enterobacteriaceae produce these AmpC enzymes (Bush-Jacoby-Medeiros group 1), including Enterobacter spp., Citrobacter freundii, Morganell a morganii, Providencia spp., and Serratia marcescens. Resistance via this mechanism has been shown to be statistically correlated with the rise of some third-generation cephalosporins, and the infections cause d by these stably derepressed enzyme-producing species seem to occur m ost frequency in the seriously ill. More recently the genes encoding t his enzyme have been documented on plasmids capable of transfer into o ther species such as Klebsiella pneumoniae. Fourth-generation cephalos porins, with stability and lo ic, affinity for the Amp C beta-lactamas es and the ability to penetrate rapidly into the periplasmic space of Gram-negative organisms, offer a viable alternative in the treatment o f these infections or as empiric regimens. Furthermore, these compound s (example: cefpirome) possess greater potency against the frequently occurring Gram-positive cocci such as oxacillin-susceptible staphyloco cci and the streptococci (including some penicillin-resistant strains) as compared to previously used anti-pseudomonal cephalosporias, cefta zidime. (C) 1998 Elsevier Science Inc.