Prevalence and mechanisms of cephalosporin resistance in Enterobacteriaceae in London and South-East England
ABSTRACT To investigate the molecular epidemiology of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in London and South-East England.
A prospective study involving 16 hospital microbiology laboratories in London and South-East England was undertaken over a 12 week period. Each laboratory submitted up to 100 consecutive cephalosporin-resistant Enterobacteriaceae isolates judged clinically significant by microbiology staff. Centralized testing was undertaken to confirm organism identification and cephalosporin resistance and to analyse resistance mechanisms.
The predominant mechanism of cephalosporin resistance in isolates from both hospital and community settings was the production of CTX-M-type ESBLs, with CTX-M-producing Escherichia coli as the most numerous resistant organism overall. Other major mechanisms of cephalosporin resistance included production of non-CTX-M ESBLs and AmpC beta-lactamases. Most ESBL (both CTX-M and non-CTX-M) producers were multiply resistant to non-beta-lactam antibiotics, including trimethoprim, ciprofloxacin and gentamicin.
CTX-M enzymes, which were unrecorded in the UK prior to 2000, have become the major mechanism of cephalosporin resistance in Enterobacteriaceae in South-East England. E. coli has overtaken Klebsiella and Enterobacter spp. to become the major host for ESBLs. Due to the multiple antibiotic resistance exhibited by many ESBL-producers, these changes have major implications for antimicrobial therapy.
Full-textDOI: · Available from: Russell Hope, May 27, 2014
SourceAvailable from: Fritz Sörgel[Show abstract] [Hide abstract]
ABSTRACT: The efficacies of tigecycline and ceftazidime against fatal pneumonia in rats caused by an extended-spectrum β-lactamase (ESBL)-positive Klebsiella pneumoniae strain or its wild-type (WT) progenitor were compared. Ceftazidime at 12.5 or 50 mg/kg of body weight twice daily (b.i.d.) was effective (50% or 100% rat survival) in pneumonia caused by the WT isolate but unsuccessful (100% rat mortality) in pneumonia caused by the ESBL-positive variant. In contrast, tigecycline at 6.25, 12.5, or 25 mg/kg b.i.d. showed dosage-dependent efficacy up to 100% rat survival irrespective of the ESBL character of the infecting organism.Antimicrobial Agents and Chemotherapy 01/2013; 57(1). DOI:10.1128/AAC.01154-12 · 4.45 Impact Factor
Article: Ceftaroline[Show abstract] [Hide abstract]
ABSTRACT: Cephalosporins are widely used antibiotics throughout the world. However, with the availability of multiple agents in this class with varying spectrum of activity and clinical use, selecting the most appropriate cephalosporin can become convoluted. Ceftaroline, a new-generation cephalosporin recently approved in the United States for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection may further complicate this dilemma. Ceftaroline is easily distinguishable compared to the other intravenous cephalosporins given its activity against methicillin-resistant Staphylococcus aureus (MRSA) including multidrug-resistant MRSA. Unfortunately, its Food and Drug Administration–approved indications offer little benefit for the antimicrobial, given cheaper, oral, and more experienced antimicrobials for these indications exist. Ceftaroline may be more appealing in the treatment of infections that require broad-spectrum intravenous antibiotics empirically (eg, endocarditis, meningitis, and osteomyelitis), especially if MRSA is a concern. However, future studies are needed to evaluate its efficacy for these indications. Until these are completed, ceftaroline should be considered as an alternative for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection at this time.Infectious Disease in Clinical Practice 01/2014; 22(1):8-17. DOI:10.1097/IPC.0b013e3182948d1c
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ABSTRACT: To describe the prevalence and risk factors for infection due to AmpC β-lactamase-producing Escherichia coli (AmpC-EC). For the prevalence study, all clinical isolates of E. coli with reduced susceptibility to third-generation cephalosporins were prospectively included from June 2010 to November 2011. For risk factor analysis, a case-control study was conducted. Cases were patients with an infection due to AmpC-EC. Controls were patients infected with cephalosporin-susceptible E. coli, matched 1 : 2. Detection of blaAmpC genes was done with a multiplex AmpC-PCR, and hyperproduction of E. coli chromosomal blaAmpC by quantitative RT-PCR. Alteration of the blaAmpC promoter was studied by PCR and sequencing. We identified 243 (1.1%) AmpC-EC strains out of 21 563 clinical isolates. Three cases with strains carrying ESBLs, 18 strains that were considered due to colonization and 8 cases lost to clinical follow-up were excluded. Finally, 214 cases were included in the analysis. Ninety-one cases (42.5%) and 269 (62.8%) controls were strictly community acquired (P < 0.001). Thirty-five (16.3%) cases and 186 controls (43.5%) did not have any identifiable risk factor (P < 0.001). Among cases, 158 (73.8%) were found to harbour an acquired AmpC (73.4% CMY-2). Previous use of fluoroquinolones [OR 2.6 (95% CI 1.12-3.36); P = 0.008] was independently associated with AmpC-EC in the multivariate analysis. Prevalence of AmpC in E. coli remains low in our area. Plasmid acquisition (CMY type) represents the main mechanism of AmpC production. A high proportion of community-acquired isolates and patients with no identifiable risk factors were found. Previous use of fluoroquinolones was identified as a risk factor. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.Journal of Antimicrobial Chemotherapy 12/2014; 70(3). DOI:10.1093/jac/dku468 · 5.44 Impact Factor