Declining cephalosporin and fluoroquinolone non-susceptibility among bloodstream Enterobacteriaceae from the UK: links to prescribing change?

Objectives: The UK saw major increases in cephalosporin and quinolone resistance amongst Enterobacteriaceae from 2001 to 2006, with cephalosporin resistance largely reflecting dissemination of CTX-M extended-spectrum beta-lactamases (ESBLs). We review subsequent trends. Methods: Data were extracted from Public Health England's national database (LabBase), which collects susceptibility results for bloodstream isolates from hospital microbiology laboratories in England, Wales and Northern Ireland, and from the BSAC Bacteraemia Resistance Surveillance System, which centrally tests bloodstream isolates from 25-40 sentinel UK and Irish laboratories. Reference laboratory submissions were also reviewed. Results: LabBase and BSAC data showed that rates of non-susceptibility to cephalosporins and quinolones rose amongst Escherichia coli and Klebsiella spp. until mid-decade (2004-07) before plateauing or falling; similar falls in non-susceptibility began slightly earlier in Enterobacter spp. These reversals in trend occurred whilst the incidence of E. coli bacteraemias was rising, the incidence of Klebsiella bacteraemias was stable and the incidence of Enterobacter bacteraemias was falling; they were not paralleled in EARS-Net data for continental Europe and did not reflect the displacement of single mechanisms. They coincided with large reductions in hospital cephalosporin and quinolone use, owing to concern about Clostridium difficile, with replacement by penicillin/beta-lactamase inhibitor combinations, which have borderline activity against ESBL producers, but consistently lack activity against carbapenemase producers. Conclusions: Non-susceptibility to cephalosporins and quinolones has declined among bloodstream Enterobacteriaceae in the UK, probably reflecting prescribing shifts. The penicillin/b-lactamase inhibitor combinations that have largely replaced cephalosporins and quinolones may add to selection for carbapenemase producers.