bla _CTX-M Genes in Clinical Salmonella Isolates Recovered from Humans in England and Wales from 1992 to 2003

Abstract

Cefotaximases (CTX-M) are a rapidly growing class A ␤-lactamase family that has been found among a wide range of clinical bacteria. One hundred and six isolates were selected from 278,308 Salmonella isolates based on resistance to ampicillin and cephalosporins and subjected to further characterization. Fourteen isolates were bla CTX-M PCR positive, and cefotaxime MICs for these isolates were >16 mg/liter. Furthermore, sequence analysis revealed the presence of type CTX-M9, -15, or -17 to -18. All 14 isolates presented different PFGE restriction profiles, although six Salmonella enterica serotype Virchow isolates formed a tight cluster. The bla CTX-M genetic determinants were present in transferable plasmids of ϳ63, 105, and >148 kb. Plasmid restriction analysis showed that both horizontal transfer of similar plasmids among different clones and transfer of genes between different plasmids were likely mechanisms involved in the spread of bla CTX-M genes. We have found that CTX-M enzymes have emerged in community-acquired infections both linked to foreign travel and domestically acquired. This is the first report of a CTX-M enzyme in Salmonella in the United Kingdom. Also, it represents the first report of a bla CTX-M gene in Salmonella enterica serotype Stanley and a bla CTX-M-15 gene in Salmonella enterica serotypes Anatum, Enteritidis, and Typhimurium.Antimicrobials are essential for the treatment of invasive infections caused by Salmonella spp. However, it is well known that these organisms have been successful at acquiring resistance to a broad range of commonly used antimicrobials (5, 6). Extended-spectrum cephalosporins and fluoroquinolones are often used in the treatment of invasive cases of salmonellosis. However, the utilization of these drugs in treating complicated Salmonella infections is becoming seriously compromised by the increasing development of fluoroquinolone and extendedspectrum cephalosporin resistance. A recent example of this is treatment failure due to in vivo acquisition of a plasmid containing the bla CTX-M-3 gene by Salmonella enterica serotype Anatum (12).Cefotaximases (CTX-M) are class A ␤-lactamases that in general present higher levels of hydrolytic activity against cefotaxime than against ceftazidime. Ceftazidime MICs for organisms producing these enzymes are sometimes in the susceptible range. Many laboratories use ceftazidime resistance alone as an indicator of extended-spectrum ␤-lactamase production. For this reason, CTX-M-producing isolates may be missed by routine susceptibility testing performed by clinical microbiology laboratories. CTX-M enzymes comprise a rapidly growing family distributed both over wide geographic areas and among a wide range of bacteria of clinical significance. There are five major CTX-M groups (groups 1, 2, 8, 9, and 25) (3).In order to assess the current presence of organisms and genes of concern in England and Wales, the present work aimed to screen a large collection of Salmonella isolates of human origin with for the presence of bla CTX-M genes. S...

Development of a multiplex PCR system and its application in detection of blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes in clinical Klebsiella pneumoniae and Escherichia coli strains

“…To further ascertain the efficiency of the new M-PCR system, each of the PCR products from the strains that tested positive for the bla group genes were subjected to direct bidirectional DNA sequencing using either the M-PCR primers or sequencing primers 24,25 (shown in Table 1). The DNA sequencing data were compared with known bla allele sequences (Lahey Clinic website: http://www.lahey.org/Studies/other.asp#table1) by multiple-sequence alignment using the ClustalW2 online program.…”

Regional outbreak of CTX-M-2 β-lactamase-producing Proteus mirabilis in Japan

“…AJ416343) have also been reported to associate with bla CTX-M-2 and bla CTX-M-9 genes (Saladin et al, 2002;Eckert et al, 2006). CTX-M enzymes have been found predominantly in members of the Enterobacteriaceae, most prevalently in E. coli, K. pneumoniae and Salmonella enterica serovar Typhimurium in South America (Radice et al, 2002;Villegas et al, 2004) and Europe (Baraniak et al, 2002;Batchelor et al, 2005;Livermore & Hawkey, 2005), although they are rarely isolated in Japan (Yagi et al, 2000). The spread of CTX-M enzyme-producing E. coli among community-and hospital-based patients has also been reported (Woodford et al, 2004).…”

Curing vector for IncI1 plasmids and its use to provide evidence for a metabolic burden of IncI1 CTX-M-1 plasmid pIFM3791 on Klebsiella pneumoniae

“…The CTX-M class of ESBLs has become the most prevalent type isolated from clinical settings (Livermore et al, 2007), and is increasingly common in community and veterinary isolates (Batchelor et al, 2005;Pitout et al, 2005). Awareness of the potential spread of this resistance in livestock has increased (Horton et al, 2011).…”