Interactions of FCE 22101 with class I beta-lactamases

Hyperproduction of chromosomal Class I beta-lactamase causes resistance to newer cephalosporins in Enterobacter cloacae, Citrobacter freundii, Serratia spp. and indole-positive Proteeae. We examined the interactions of FCE 22101 with these enzymes, measuring (i) antibiotic lability to pure enzyme, (ii) inducing power and (iii) activity against beta-lactamase-inducible strains and their -depressed and -basal mutants. Turnover numbers of FCE 22101 were between 0.7 and 1.5 molecules hydrolysed/min/enzyme molecule, compared with ranges of 0.5-40 for cefotaxime (950 for the Proteus vulgaris cephalosporinase) and 4400-22,000 for cephaloridine. FCE 22101 induced enzyme synthesis strongly below the MIC and antagonized labile weak inducers such as cefotaxime and mezlocillin. Like imipenem, but unlike newer cephalosporins, FCE 22101 had equal activity against inducible strains and derepressed mutants, and did not significantly select derepressed mutants from inducible populations. beta-Lactamase basal mutants of E. cloacae and C. freundii were four- to eight-fold more sensitive than inducible and derepressed organisms whereas beta-lactamase-basal, -inducible and -derepressed Proteeae and Serratia spp. were equally sensitive. This difference reflected the larger amounts of enzyme produced by the E. cloacae and C. freundii strains, rather than kinetic differences in enzyme activity.