Detection of Pseudomonas aeruginosa isolates producing VEB-type extended-spectrum β-lactamases in the United Kingdom

Objectives: The aim of this study was to investigate the presence of VEB enzymes among Pseudomonas spp. referred to the UK's national reference laboratory and with phenotypic evidence of extended-spectrum β-lactamase (ESBL) production. Methods: Antibiograms were analysed for Pseudomonas spp. referred from November 2003 to November 2007. Isolates with ≥4-fold ceftazidime/ clavulanate synergy were screened for bla_VEB alleles. Genes encoding metallo-β-lactamases (bla_MBL) were sought in isolates with positive imipenem/EDTA synergy tests. Selected PCR products were sequenced. PFGE of Spe I-digested genomic DNA was used to compare isolates. Results: Forty-nine (3.7%) of 1338 Pseudomonas spp. were considered potential ESBL producers; 40 were recovered for molecular testing. bla_VEB alleles were detected in 32 Pseudomonas aeruginosa isolates, comprising diverse PFGE types, from 12 UK hospitals and 1 in India. One UK centre referred 15 isolates with VEB-1 enzyme; these were serotype O15, representing a single PFGE-defined strain that also produced VIM-10 metallo-carbapenemase. This strain was resistant to all β-lactams, aminoglycosides and ciprofloxacin, remaining susceptible only to colistin (MICs ≤1 mg/L). Two other P. aeruginosa isolates co-producing both VEB and VIM enzymes were received from two other UK hospitals; one isolate represented inter-hospital spread of the O15 strain and the second was distinct. Conclusions: VEB enzymes have not been reported previously in the UK, but were produced by 80% of Pseudomonas spp. with phenotypic evidence of ESBL production. They co-existed with VIM carbapenemases in two strains, with one responsible for a major hospital outbreak. The incidence of ESBLs may be underestimated in Pseudomonas because ESBL phenotypes can be masked by other β-lactam resistance mechanisms.