Characterization and Prevalence of the Different Mechanisms of Resistance to Beta-Lactam Antibiotics in Clinical Isolates of Escherichia coli

Abstract

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-,8-lactamase which resembled RTEM and was located behind a permeability barrier to penicillins but not to cephalosporins. This permeability barrier appeared to act synergistically with the ,B-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 ,8-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 E) were found to have low levels of different ,8-lactamases including a transferable ,8-lactamase which resembled R,,,6. Thus, different mechanisms producing resistance to ,B-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.

Outer-Membrane Penetration Barriers as Components of Intrinsic Resistance to Beta-Lactam and Other Antibiotics in Escherichia coli K-12

“…The BI's of penicillin, ampicillin, and cloxacillin were at least tenfold higher than predicted, although the other beta-lactams were close to the regression line; the reasons for these differences are not known. The lack of a penetration barrier for cephaloridine has been noted in other studies (16,27,38). The affinities of benzylpenicillin, ampicillin, cephalothin, and cephaloridine for the lysis-promoting target site(s) of Y10 are largely compatible with findings based on competitive binding 188 SCUDAMORE, BEVERIDGE, AND GOLDNER of beta-lactams to the isolated penicillin-binding protein 1 of E. coli (32).…”

A Possible Role of R Plasmids in Bacterial Permeability for β‐Lactam Antibiotics

“…It is known that a variety of mechanisms such as enzymatic inactivation, permeability barrier, irreversible binding to a strategically placed enzyme including f1-lactamases (trapping of antibiotics), and alteration of the target site of antibiotics are involved in bacterial resistance to f1-lactam antibiotics (2,4,12,14,(19)(20)(21). It is true that enzymatic inactivation and hydrolysis by f1-lactamases play the leading role in the drug-resistance mechanisms.…”

“…Since many ,8-lactam antibiotics resistant to hydrolysis by ,8-lactamases have been developed recently (5,7,17), it is possible that mutants acquiring resistance mechanisms other than ,8-lactamase production selectively appear. In fact, Medeirous et al (14) presented some evidence that the resistance of a few strains of Escherichia coli to ampicillin and to carbenicillin was due to their low permeability for the antibiotics. From this point of view, we studied the pos-333 sibility that R plasmids isolated from clinical isolates of Serratia marcescens might contribute to bacterial permeability for p-lactam antibiotics.…”

Relation of Beta-Lactamase Activity to Antimicrobial Susceptibility in Serratia marcescens

“…However, it has been shown (15) Cultures. The S. marcescens isolates used in this study were obtained from a variety of clinical specimens, submitted to departments of Bacteriology, Mayo Clinic, Rochester and University of Illinois Hospital, Chicago.…”