Background:

Extended-spectrum b-lactams are commonly included in empirical antibiotic regimens for the treatment of Gram-negative infections. The emergence of extended spectrum b-lactamase (ESBL)-producing bacteria poses a serious threat to the continued use of this family of antibiotics. Since ESBLs have previously been uniformly susceptible to b-lactamase inhibitors (e.g. tazobactam or clavulanic acid), inhibitor/b-lactam combinations (e.g. piperacillin/tazobactam) have been advocated as potential therapeutically effective agents.

Methods:

In June 2003, a clinical isolate of Escherichia coli was recovered from a 82-year-old woman nursed on the high dependency surgical ward in St James's University Hospital Leeds, UK. The patient had received courses of ceftazidime and piperacillin/tazobactam (Pip/Taz). The organism was isolated from a urine specimen. Speciation was confirmed biochemically with API 20E system. The organism was resistant to ceftazidime, cefotaxime, aztreonam, Pip/Taz and amoxicillin/clavulanic acid and was susceptible to meropenem, imipenem and cefoxitin using a disk diffusion method. ESBL production was sought using the disc synergy and the MAST ID tests. PCR using specific primers was used to screen for the presence of blaSHV and blaTEM. Nucleotide sequence analysis was used to determine the identity of the resistance determinants.

Results:

ESBL production was demonstrated with both the disc synergy and the MAST ID tests. PCR showed the organism to harbour a blaTEM. Nucleotide sequence analysis identified the resistant determinant as a TEM-26 b-lactamase with an additional mutation at amino-acid position 69 with the replacement of methionine by valine. This mutation has previously been shown to confer resistance to beta-lactamase inhibitors.

Conclusions:

To our knowledge this is the first report of a TEM extended-spectrum b-lactamase also conferring resistance to Pip/Taz. This highlights the continuing global emergence and mutability of this clinically important family of enzymes. It emphasises the importance for vigilance in identifying novel resistance mechanisms and the need for prudent use of antimicrobials to preserve their clinical efficacy.