In Vitro Activity of Piperacillin/tazobactam and Other Broad-spectrum Antibiotics Against Bacteria from Hospitalised Patients in the British Isles

Piperacillin/tazobactam is used for empirical therapy of severe and complex infections. We assessed its activity, 9 years after launch, against consecutive, clinically significant isolates from in-patients in UK and Ireland. Standardised disc susceptibility tests were performed on 5031 isolates at 28 hospitals. For quality assurance purposes, 5% of these isolates were collected centrally for MIC tests, as were those with exceptional resistances. Compared with a similar pre-launch survey in 1991, there were major increases in the proportions of Staphylococcus aureus, Pseudomonas aeruginosa, beta-haemolytic streptococci and Enterococcus faecium isolates collected, balanced by decreases in Escherichia coli, Proteus mirabilis and coagulase-negative staphylococci. These changes in species prevalence mostly favoured organisms with inherent resistance(s) or-in the case of S. aureus-reflected the massive increase of MRSA, up from 0.7% of all isolates in 1991 to 14.8% in 2001. Based on the disc tests, piperacillin/tazobactam retained activity against 87% of Enterobacteriaceae isolates, 95% of P. aeruginosa, 99% of streptococci and 96% of Enterococcus faecalis. Resistance nevertheless had increased since 1991 in E. coli from 4 to 10%, Klebsiella spp. (5 to 21%) and in AmpC-inducible Enterobacteriaceae (17 to 23%), though not in P. mirabilis or P. aeruginosa. MIC tests confirmed most of the piperacillin/tazobactam resistance found by disc tests in Enterobacter spp., but indicated susceptibility for about half of the E. coli isolates recorded as resistant in disc tests. This situation might be remedied by reducing the zone breakpoint, but this would increase the "false susceptible" rate unacceptably. Thus, if disc tests suggest that an isolate is marginally resistant to piperacillin/tazobactam and the drug is sought as therapy, it is recommended that MIC be determined with, e.g., an Etest.