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A survey of clinical isolates from a hospital laboratory showed that Escherichia coli could be grouped into three classes of beta-lactam-antibiotic resistance by results of routine susceptibility testing to ampicillin, cephalothin, and carbenicillin. E. coli highly resistant to ampicillin and carbenicillin but not to cephalothin (class I) were found to have one of two levels of R factor-mediated, periplasmic-beta-lactamase which resembled R(TEM) and was located behind a permeability barrier to penicillins but not to cephalosporins. This permeability barrier appeared to act synergistically with the beta-lactamase in producing high levels of resistance to penicillins. E. coli highly resistant to ampicillin and cephalothin but not carbenicillin (class II) were found to have a beta-lactamase with predominantly cephalosporinase activity which was neither transferable nor releasable by osmotic shock. E. coli moderately resistant to one or to all three of these antibiotics (class III) were found to have low levels of different beta-lactamases including a transferable beta-lactamase which resembled R(1818). Thus, different mechanisms producing resistance to beta-lactam antibiotics could be deduced from the patterns of resistance to ampicillin, cephalothin, and carbenicillin found on routine susceptibility testing. E. coli of class I were much more prevalent than the other classes and the proportion of E. coli that were class I increased with duration of patient hospitalization. The incidence of class I E. coli rose only slightly over the past 7 years and that of class II E. coli remained constant despite increased usage of both cephalothin and ampicillin. These observations emphasize that the properties of the apparently limited number of individual resistance mechanisms that exist in a bacterial flora, such as their genetic mobility and linkages and the spectrum of their antibiotic inactivating enzymes and permeability barriers, may govern the effect that usage of an antibiotic has upon the prevalence of resistance to it and to other antibiotics.

The Enterobacter species E. aerogenes, E. cloacae, and E. hafnia were examined for resistance to penicillin and cephalosporin derivatives. All were resistant to benzyl penicillin, ampicillin, 6 [d(-)alpha-amino-p-hydroxyphenylacetamido] penicillanic acid, cephaloridine, cephalothin, and cephalexin. A significant number were sensitive to carbenicillin and 6 [d(-)alpha-carboxy-3-thienylacetamido] penicillanic acid. No differences among the three species were noted. The beta-lactamase activity was cell-bound, and was not released by osmotic shock, toluene treatment, or diphenylamine treatment. It was rarely released into the growth medium. The beta-lactamase activity was primarily directed against cephalosporin derivatives. Synthesis of beta-lactamase was chromosomally mediated. Resistance to ampicillin seemed to be partly related to entry of the molecule into the bacteria since exposure to ethylenediaminetetraacetate lowered the minimal inhibitory concentration.