Characterization of AmpC-Mediated Resistance in Clinical Salmonella Isolates Recovered from Humans during the Period 1992 to 2003 in England and Wales

Abstract

The increase in AmpC-mediated resistance in salmonellae constitutes a serious public health concern, since these enzymes confer resistance to a wide range of ␤-lactams. One hundred six isolates were selected from 278,308 Salmonella isolates based on resistance to ampicillin and cephalosporins and were subjected to further characterization. Nine isolates had a cefoxitin inhibition diameter <17 mm and were proven to be AmpC positive by multiplex PCR. Sequence analysis revealed the presence of bla DHA-1 , bla CMY-2 , and bla CMY-4 genes. All nine isolates presented different pulsed-field gel electrophoresis restriction profiles. The AmpC genetic determinants were present in transferable plasmids of around 11, 42, 70, 98, and 99 MDa. A combination of size and restriction fragment length polymorphism (RFLP) analysis showed that all the bla CMY plasmids investigated in our study were different, which suggests that bla CMY may be located in different plasmid environments. Some United Kingdom isolates linked to foreign travel showed RFLP plasmid patterns consistent with plasmids previously seen in the United States, which suggests that bla CMY-2 has also been disseminated through plasmid transfer. The fact that two of the domestically acquired United Kingdom isolates presented previously unseen RFLP plasmid patterns could indicate that these strains have followed routes different from those prevalent in North America or other parts of the world. This study represents the first report of bla CMY genes in Salmonella isolates in the United Kingdom and the first report of CMY-4 in Salmonella enterica serotype Senftenberg worldwide.Plasmid-mediated AmpC ␤-lactamases originate from the transfer of chromosomal genes onto plasmids. This transfer has resulted in plasmid-mediated AmpC enzymes in isolates of Escherichia coli, Klebsiella pneumoniae, Salmonella spp., Citrobacter freundii, Enterobacter aerogenes, and Proteus mirabilis. These plasmid-mediated ␤-lactamases have similar substrate profiles to the parental enzymes from which they appear to be derived, although the vast majority are noninducible. Several AmpC-type enzymes have been described including FOX, MOX, CMY, DHA, ACC, MIR, ACT, and LAT. Of particular interest in Salmonella are the CMY enzymes, especially CMY-2. There are currently 13 bla CMY genes identified, falling into two distinct groups based on DNA sequence homology. One group includes the genes CMY-2 to -7, LAT-1 to -4, and BIL-1 and originates from C. freundii (21), while the second group includes the genes for MOX-1 and -2, CMY-1, and CMY-8 to -11 and has an unknown origin (21). CMY-2 was first identified in a human clinical case of K. pneumoniae from Greece (4). Since then, CMY-2 has been identified in a large number of different human and animal Salmonella serovars (Newport [22] Most Salmonella infections result in moderate gastroenteritis, which resolves spontaneously. However, systemic infections, such as bacteremia and meningitis, may also develop and require antibiotic treatment. These invasive infec...

Characterisation of CTX-M and AmpC genes in human isolates of Escherichia coli identified between 1995 and 2003 in England and Wales

“…In agreement with this observation, these two plasmids transferred a resistance phenotype not only to ␤-lactams but also to other classes of antimicrobials (see Table 2). CMY-2 plasmids from E108137 and E128986 appear to be new types and were different to those seen in UK Salmonella [39], suggesting that bla CMY-2 in some UK E. coli may be located on different plasmid backbones than in Salmonella from the UK and USA. CMY-2 plasmids have been shown to transfer between Salmonella and E. coli and to be transmitted between food animals and humans [40].…”

AmpC β-Lactamases

“…When treatment is indicated, fluoroquinolones are as effective as they are with pansusceptible Salmonella strains (74), but a few strains that are resistant to both fluoroquinolones and extended-spectrum cephalosporins have appeared (338). CMY-2-producing nontyphoid Salmonella strains have been isolated in other countries, as have Salmonella strains producing AmpC ␤-lactamases CMY-4, CMY-7, ACC-1, and DHA-1 (19,135,213,314). CMY producers belong to several serogroups, with Salmonella enterica serovars Typhimurium and Newport (113) being the most common.…”

Broad-spectrum β-lactamases amongEnterobacteriaceaeof animal origin: molecular aspects, mobility and impact on public health

“…The different surveillance programmes around the world have made it possible to obtain good knowledge of β‐lactam usage in food and non‐food animals (Schwarz & Chaslus‐Dancla, 2001; Schwarz et al , 2001; Guardabassi et al , 2008; CDC, 2004; Batchelor et al , 2005a, b; Li et al , 2005; CIPARS, 2006; DANMAP, 2006; McEwan & Fedorka‐Cray, 2006; Lloyd, 2007; Hammerum & Heuer, 2009). By way of summary, ampicillin and amoxicillin are regarded as the drugs of choice in avian medicine in many continents.…”