What do beta-lactamases mean for clinical efficacy?

beta-Lactamases have proved to be extremely important in influencing therapy with penicillins and cephalosporins against gram-positive and gram-negative aerobic and anaerobic species. Both plasmid mediated beta-lactamases which are primarily of a constitutive penicillinase type and the inducible chromosomal enzymes which are primarily cephalosporinases are important. The use of penicillins to treat Haemophilus, Neisseria gonorrhoeae, Escherichia coli, Klebsiella, Salmonella, Shigella and Pseudomonas infections must be based upon the relative incidence of beta-lactamase producing strains. In the same manner cephalosporins can be used to treat infections due to Enterobacter, Serratia and Bacteroides only if the compounds are beta-lactamase stable and not good inducers of beta-lactamase activity. Although altered permeability is important in the resistance of some Pseudomonas and Enterobacter to beta-lactams, the resistance really is due to a combination of reduced entry of molecules and strategically placed beta-lactamases. It is only in some Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and Streptococcus faecalis strains that altered penicillin-binding proteins make a significant contribution to the resistance to beta-lactams. beta-lactamases will continue to be the most important factor in clinically significant resistance of bacteria to both penicillins and cephalosporins.