Relationship Between beta-Lactamase Activity and Resistance of Enterobacter to Cephalothin

The relationship between cephalosporin β-lactamase activity and resistance to cephalothin was investigated in strains of Enterobacter cloacae and E. aerogenes. β-Lactamase activity was detected in all strains, but a quantitative correlation between amount of β-lactamase activity and level of resistance to cephalothin was not observed. Permeability barriers to cephalothin were observed and varied from strain to strain. β-Lactamase activity was increased by growing organisms in the presence of penicillin G. These enzymes hydrolyzed cephalosporins more rapidly than penicillins. Penicillinase-resistant penicillins, especially those of the isoxazolyl series, effectively inhibited Enterobacter β-lactamase. A synergistic antibacterial effect was observed when organisms were exposed to cephalothin and oxacillin in combination, and the resistance of even very small inocula to cephalothin was reduced by addition of oxacillin. Oxacillin probably exerts its effect by inhibiting β-lactamase at an intracellular site. Intracellular β-lactamase may make an important contribution to the resistance of even small inocula of gram-negative bacilli to cephalosporin and penicillin antibiotics. Although β-lactamase plays a significant role in the resistance of Enterobacter to cephalothin, other factors, such as permeability barriers, also participate in determining the level of resistance.