AmpC β-Lactamases

Abstract

SUMMARY AmpC β-lactamases are clinically important cephalosporinases encoded on the chromosomes of many of the Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor-β-lactam combinations. In many bacteria, AmpC enzymes are inducible and can be expressed at high levels by mutation. Overexpression confers resistance to broad-spectrum cephalosporins including cefotaxime, ceftazidime, and ceftriaxone and is a problem especially in infections due to Enterobacter aerogenes and Enterobacter cloacae, where an isolate initially susceptible to these agents may become resistant upon therapy. Transmissible plasmids have acquired genes for AmpC enzymes, which consequently can now appear in bacteria lacking or poorly expressing a chromosomal blaAmpC gene, such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Resistance due to plasmid-mediated AmpC enzymes is less common than extended-spectrum β-lactamase production in most parts of the world but may be both harder to detect and broader in spectrum. AmpC enzymes encoded by both chromosomal and plasmid genes are also evolving to hydrolyze broad-spectrum cephalosporins more efficiently. Techniques to identify AmpC β-lactamase-producing isolates are available but are still evolving and are not yet optimized for the clinical laboratory, which probably now underestimates this resistance mechanism. Carbapenems can usually be used to treat infections due to AmpC-producing bacteria, but carbapenem resistance can arise in some organisms by mutations that reduce influx (outer membrane porin loss) or enhance efflux (efflux pump activation).

Co-production of ESBL and AmpC β-Lactamases in Clinical Isolates of A. baumannii and A. lwoffii in a Tertiary Care Hospital From Northern India

“…Acinetobacter inherently produces chromosomally mediated AmpC type cephalosporinases which are also known as Acinetobacter derived cephalosporinases (ADCs), which mediate resistance to cephalothin, cefazolin, cefoxitin, most of the penicillins and β-lactamase inhibitor β-lactam combinations. More than 25 varieties of AmpC β-lactamases that share ≥ 94% protein sequences have been described for Acinetobacter spp [4].…”

“…Acinetobacter inherently produces chromosomally mediated AmpC type cephalosporinases which are also known as Acinetobacter derived cephalosporinases (ADCs), which mediate resistance to cephalothin, cefazolin, cefoxitin, most of the penicillins and β-lactamase inhibitor β-lactam combinations. More than 25 varieties of AmpC β-lactamases that share ≥ 94% protein sequences have been described for Acinetobacter spp [4].PER-1 was the first ESBL to be reported in A. baumannii and strains harbouring PER-1 demonstrate a high level resistance to penicillins and extended spectrum cephalosporins, but it fortunately does not confer resistance to carbapenems. Routine detection of strains harbouring ESBLs may be difficult, because the synergy existent between third-generation cephalosporins and clavulanic acid, which is typically observed with ESBL-producing Enterobacteriaceae, which tends to be minimal with Acinetobacter spp.…”

An ancient family of mobile genomic islands introducing cephalosporinase and carbapenemase genes in Enterobacteriaceae

“…Automated resistance analysis with the VITEK 2 system revealed increased MIC values to the carbapenems meropenem (8 mg/L) and imipenem (8 mg/L), which were subsequently confirmed by Etests. Imipenem Etests on MHA with or without 250 mg/L cloxacillin revealed that imipenem resistance was significantly reduced in the presence of cloxacillin, which is an inhibitor of β-lactamases of the AmpC-type [17]. Specifically, the MIC was reduced to 0.125 mg/L (Figure 1).…”

Actualización de la resistencia a antimicrobianos de bacilos Gram negativos aislados en hospitales de nivel III de Colombia: años 2006, 2007 y 2008

“…Al igual que para E. coli y K. pneumoniae productores de BLEE, los carbapenems son la primera opción terapéutica para infecciones graves causadas por bacterias productoras de AmpC (25). La resistencia de Enterobacteriaceae a carbapenems es muy inusual, menor de 5% en nuestro estudio, y se reporta ya que es importante en el tratamiento de infecciones producidas por bacterias multirresistentes y por ser un marcador para la aparición de carbapenemasas, especialmente de la KPC (Klebsiella pneumoniae carbapenemase) en nuestro país (10,26).…”