title: Beta-lactamases in Enterobacteriaceae infections in children.
abstract: Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections.
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK; Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP, UK. Electronic address: cmoxon@liverpool.ac.uk.
authors.forename: Christopher Alan
authors.initials: CA
authors.lastname: Moxon
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK; Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP, UK. Electronic address: Stephane.Paulus@alderhey.nhs.uk.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Paulus
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000096:biosynthesis; D002648:Child; D003091:Colistin / Q000008:administration & dosage / Q000627:therapeutic use; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D005578:Fosfomycin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005578:Fosfomycin; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; C063912:carbapenemase; D003091:Colistin
keywords: AmpC beta-lactamases; Antimicrobial resistance; Carbapenemase producing Enterobacteriaceae; Enterobacteriaceae; Extended β-lactamase producers; Paediatrics