Non-susceptibility trends among Enterobacteriaceae from bacteraemias in the UK and Ireland, 2001-06

Background: Enterobacteriaceae are common agents of bacteraemia, with Escherichia coli accounting for 20% of the cases. Reflecting this importance, members of the family constitute 4 of the 12 collection groups in the British Society for Antimicrobial Chemotherapy (BSAC) Bacteraemia Surveillance Programme. Methods: MICs from the BSAC surveillance programme were reviewed, along with bacteraemia reports received by the Health Protection Agency (HPA) via its CoSurv/LabBase system. Isolates with unusual resistances were subjected to molecular analysis. Results: The BSAC and HPA systems both revealed dramatically increasing resistance to cephalosporins, ciprofloxacin and gentamicin among E. coli and Klebsiella spp., with cephalosporin resistance largely contingent on the spread of CTX-M extended-spectrum β-lactamases (ESBLs); fluoroquinolone resistance also increased among Proteus mirabilis and ESBL-negative E. coli. Carbapenem resistance remained extremely rare, but two Enterobacter spp., from the same patient in different years, had KPC carbapenemases, while a few isolates had carbapenem resistance contingent upon combinations of β-lactamase and impermeability, and ertapenem MICs for AmpC-derepressed Enterobacter spp. rose over time. Three new agents - ceftobiprole, doripenem and tigecycline - were tested. Ceftobiprole was broadly active, except against ESBL producers and Klebsiella oxytoca hyperproducing K1 enzyme, and was variable against AmpC-derepressed Enterobacter spp. and against Proteus vulgaris. Doripenem was more potent than imipenem. Tigecycline was almost universally active against E. coli, but low-level non-susceptibility (MIC 2 mg/L) was frequent among Klebsiella spp. Conclusions: E. coli and Klebsiella spp. showed dramatic shifts, with sharply rising non-susceptibility to cephalosporins, ciprofloxacin and gentamicin. The rise in cephalosporin resistance reflected dissemination of CTX-M ESBLs. Carbapenems remain broadly active and new agents offer potential.