AmpC type β-lactamases are such type of beta-lactamases which are not inhibited by clavulanic acid but are inhibited by boronic acid. These are clinically important cephalosporinases encoded on the chromosomes of many Enterobacteriaceae and a few other organisms. In such organisms they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor/β-lactam combinations. The plasmid-borne AmpC beta-lactamases were found in bacteria such as Escherichia coli and Klebsiella spp in the late 1980s [1,2]. However, the first bacterial enzyme reported to destroy penicillin was the AmpC β-Lactamase of Escherichia coli dated back in 1940 without its specific name to be called as AmpC β-Lactamase. The systematic study of the genetics of penicillin resistance in E. coli began in 1965.
With the exception of the AmpC β-lactamase of Psychrobacter immobilis (secreted mainly into the external medium), majority of the enzymes are located in the bacterial periplasm [3].
AmpC type β-lactamases can be mediated either by chromosome or plasmid. The plasmid mediated AmpC β-lactamases can hydrolyze all β-lactam except cefepime and carbapenem. These genes are derived from inducible chromosomal genes being mobilized in various organism. The commonly reported genotypes are ACC, FOX, MOX, DHA, CMY, CIT and EBC [5,6 and 7].
The identication technique of AmpC β-lactamase-producing isolates are still evolving and are not yet optimized for the clinical laboratory because of which has underestimated mechanisms of these resistance. Carbapenems can usually be used to treat infections due to AmpC-producing bacteria, but carbapenem resistance can arise in some organisms by mutations. These mutations either reduce influx (outer membrane porin loss) or enhance efflux (efflux pump activation).
The regular testing procedure includes three dimensional extract test, AmpC disk test, Boronic acid disk test and disk approximation test phenotypically. These phenotypic tests do not differentiate between chromosomal and plasmid mediated AmpC β-lactamases. Hence, plasmid-mediated AmpC β-lactamases are mostly detected with the multiplex AmpC PCR test involving specific primer for the genes that induces the resistance.
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| Fig. 1: Representation of positive boronic acid disk test.Left: 30 μg cefoxitin disk supplemented with 300μg of phenyl boronic acid. Right: 30 μg cefoxitin disk alone. [Interpretation: An organism that demonstrates a defined increase (≥5-mm) in zone diameter around the antibiotic disk with added boronic acid consider to be an AmpC producer.] |
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