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Category: Bacterial Pathogenesis
β-Lactam Resistance in the 21st Century, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555817572/9781555813291_Chap05-1.gif /docserver/preview/fulltext/10.1128/9781555817572/9781555813291_Chap05-2.gifAbstract:
The β-lactamase community currently recognizes two major classification schemes based either on function or structure. Historically, these enzymes were separated according to biochemical activities, with classification based on hydrolysis of specific substrates and the sensitivity to selected inhibitors. After penicillin was used more frequently in post-World War II medicine, the incidence of penicillinase-producing Staphylococcus aureus increased in one British hospital from ≥8% in 1945 to almost 60% of clinical isolates in less than five years. Examples of apparent cause and effect relationships include the discovery of cephalosporin C and subsequent introduction of cephalosporin analogs, together with the introduction of broad-spectrum penicillins, such as ampicillin, leading to the identification of plasmid-encoded broad-spectrum penicillinases such as TEM-1. This ubiquitous β-lactamase among the Enterobacteriaceae, with the ability to hydrolyze not only many penicillins but also the early cephalosporins such as cephalothin, became the most prevalent plasmid-encoded enzyme in epidemiological surveys of the late 1970s and early 1980s. In the compilation shown, geographical areas reasonably close to each other sometimes exhibit different regional enzyme patterns. The level of β-lactam resistance produced by an enzyme is determined by a number of factors besides its intrinsic hydrolytic activity. β-Lactamases are ancient enzymes, widespread in the microbial world, that in recent years have coevolved with β-lactam antibiotics as aminopenicillins, cephalosporins, cephamycins, oxyimino-cephalosporins, monobactams, and carbapenems have been developed to target new pathogens or to overcome existing resistance.
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Effects of newly introduced β-lactam-containing agents on β-lactamase populations.
Effects of newly introduced β-lactam-containing agents on β-lactamase populations.
Functional groups of (3-lactamases based on Bush, Jacoby, and Medeiros scheme (16)
a With exceptions for particular enzymes.
b IC50 of clavulanic acid that were >10 µM were considered to be Clav( —). IC50 that were <1 µM were considered to be Clav(+). IC50 that were <1 µM for tazobactam are TZB (+).
c ESBL, extended-spectrum β-lactamase.
d IRTs, inhibitor-resistant TEM β-lactamases.
e New group not included in reference 16. Note that functional group 4 enzymes are not included, as this group has not been fully characterized.
Functional groups of (3-lactamases based on Bush, Jacoby, and Medeiros scheme (16)
a With exceptions for particular enzymes.
b IC50 of clavulanic acid that were >10 µM were considered to be Clav( —). IC50 that were <1 µM were considered to be Clav(+). IC50 that were <1 µM for tazobactam are TZB (+).
c ESBL, extended-spectrum β-lactamase.
d IRTs, inhibitor-resistant TEM β-lactamases.
e New group not included in reference 16. Note that functional group 4 enzymes are not included, as this group has not been fully characterized.
Known cassette-associated β-lactamase genes
Known cassette-associated β-lactamase genes
Likely origin of some plasmid-mediated bla genes
Likely origin of some plasmid-mediated bla genes
Reported regional occurrence of plasmid-encoded β-lactamases or β-lactamase families
a Includes Croatia, France, Greece, Italy, and Portugal.
b Two different enzymes in geographically separated regions (141; Quinn and Queenan, personal communication).
Reported regional occurrence of plasmid-encoded β-lactamases or β-lactamase families
a Includes Croatia, France, Greece, Italy, and Portugal.
b Two different enzymes in geographically separated regions (141; Quinn and Queenan, personal communication).
Susceptibility (S) and resistance (R) breakpoints for dilutional or disk susceptibility testing and recommended screening parameters for ESBL detection by the CLSI and British Society for Antimicrobial Chemotherapy (BSAC)
a For E. coli and Klebsiella spp. (2).
Susceptibility (S) and resistance (R) breakpoints for dilutional or disk susceptibility testing and recommended screening parameters for ESBL detection by the CLSI and British Society for Antimicrobial Chemotherapy (BSAC)
a For E. coli and Klebsiella spp. (2).