Although all of them are beta-lactamases, there are differences among them.
Extended spectrum beta lactamases (ESBL) hydrolyse oxyimino beta lactams like ceftazidime, cephotaxime, ceftriaxone and monobactum but have no effect on cephamycins carbapener and related compounds.
The variety of β-lactamases with wide spectra of substrate specificity illustrates the drug resistance mechanisms. Three major groups of these enzymes are usually distinguished, class C cephalosporinases (AmpC), extended-spectrum β-lactamases (ESBLs) and different types of β-lactamases with carbapenemase activity, of which the so-called class B metallo-β-lactamases (MBLs) are of the greatest concern.
AmpC β-lactamase production is one of the mechanisms of resistance to β-lactam antibiotics in Gram negative bacteria conferring resistance to a wide variety of β-lactam antibiotics including 7-α-methoxy cephalosporins (cefoxitin or cefotetan), oxyimino cephalosporins (cefotaxime, ceftazidime, ceftriaxone), monobactam (aztreonam) and are not inhibited by clavulanic acid.
Resistance in bacteria to carbapenems is due to the production of carbapenem hydrolyzing enzymes called carbapenemases. Klebsiella pneumonia carbapenemase (KPC) was first identified in 2000 among the isolates of K. pneumonia. The emergence of carbapenem resistance in K. pneumoniae has become a substantial clinical problem, most typically attributed to production of KPC.
Carbapenem resistance in K. pneumoniae may be due to other causes; these include β-lactamase production and the production of metallo-β–lactamases (MBL).
beta-lactamases are classified by two different schemes: according to structural homology (Ambler's Classification) or hydrlytic properties (Bush's and Jacoby's classification).
According to the Ambler's classification, there are 4 groups of beta-lactamases:
Group A: which regroups penicillinases (which hydrolyze generally only penicillins and sometimes early-generation cephalosporins), extended-spectrum beta-lactamases (ESBL) which hydrolyze late-generation cephalosporins (such as CTX-M-type) and class A carbapenemases which hydrolyze penicillins, cephalosporins and carbapenems (KPC for Klebsiella penumoniae carbapenemase belongs to this group).These enzymes are inhibited or partially inhibited by class A inhibitors such as Clavulanate or tazobactam.
Group C: AmpC or cephalosporinases which exhibits a greater hydrolysis for cephalosporins in comparison to benzylpenicillin. Among representative enzymes, you can found CMY-family AmpC.
Group D: Oxacillinase regroups enzyme able to hydrolyze cloxacillin or oxacillin. It’s a wide group of beta-lactamase and some of them can hydrolyse carbapenem such as e.g. OXA-48 or OXA-23.
The last group group B or metallo-beta-lactamase (MBL) differs from the three others by the fact that they possess in the active site metallic ions whereas group A, C and D are serine-active enzymes. This group exhibits a broad-spectrum hydrolysis including all beta-lactams except aztreonam and these enzymes are not inhibited by clavulanate/tazobactam. Among these enzymes, NDM-, VIM- and IMP-type are widely distributed.
The following slides are part of the presentation at the CDS workshop of the 2013 Australian Society for Microbiology Annual Scientific Meeting to illustrate the recognition of these beta-lactamases.
The following slides, illustrating the beta-lactamases, can also be viewed using the link.
http://web.med.unsw.edu.au/cdstest
As per AMBLER's classification of Beta lactamases there are 4 groups : A,B,C,D
A,C,D have serine at their active site and B have zinc and metal ions at their active site.
usually A(TEM/SHV/CTXM) & D are plasmid mediated and B &C are chromosomal.
Class A & D undergo mutation to produce ESBLs.
- Class A/D: Resistant to Penicillin,Cephalosporins and monobactams but sensitive to Betalactamase inhibitors , cephamycins and carbapenems.
- Class A/DESBLs : Resistant to Penicillin,Cephalosporins and monobactams, cephamycins - may or may not be resistant to Betalactamase inhibitors - sensitive to carbapenems
- Class B are called MBLs (Metallo-betalactamases) : Resistant to Penicillin, Cephalosporins, Betalactamase inhibitors , cephamycins and carbapenems but sensitive to monobactams (aztreonam) only.
- Class C are called AmpC betalactamases : Plasmid induced enzymes : Resistant to Penicillin, cephalosporins 1st,2nd and 3rd generations, beta lactamase inhibitors, cephamycins but sensitive to 4th generation cephalosporins and carbapenem
Extended-Spectrum-β-Lactamase, AmpC, and Carbapenemase Issues
Kenneth S. Thomson
What are ESBL?
ESBL stands for “extended-spectrum beta-lactamases” and designates enzymes which alter a broad spectrum of beta-lactam antibiotics, thus making them ineffective. Bacteria which produce these enzymes become insensitive (resistant) to important active substances such as aminopenicillins (e.g. ampicillin), cephalosporins (including those of the third and fourth generation) and monobactams. This resistance can be detected in various bacteria species, in particular enterobacteria which include Salmonella, Klebsiella and Escherichia coli among others. The genes for these enzymes lie on transmissible gene sections and can be ex- changed between bacteria of the same type or of different types (horizontal gene transfer).
What are AmpC?
AmpC beta-lactamases (AmpC) are enzymes which convey resistance to penicillins, second and third generation cephalosporins and cephamycins. They also result in resistance to combinations of these antibiotics and substances which are actually intended to inhibit the effect of beta-lactamases. They do not convey resistance to fourth generation cephalospor- ins. The genes for these enzymes occur naturally in some bacteria species as so-called chromosomal AmpC (e.g. in E. coli, but not in Salmonella up to now). The enzymes are only actually formed and only become effective under certain conditions. The important thing is the increasing number of AmpC genes localised outside the chromosome on so-called plas- mids, which is why they are often referred to as ”plasmidic AmpC” (pAmpC). They ensure the constant formation of the enzyme and lie on transmissible gene sections. These can be ex- changed between bacteria of the same type or of different types (horizontal gene transfer).
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