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Objectives Although carbapenem susceptibility testing has been recommended for all Enterobacteriaceae from clinical specimens, for practical reasons a carbapenem is not included in many primary antibiotic panels for urine specimens. The 'iCREST' study sought carbapenemase-producing Enterobacteriaceae (CPE) in routine urine specimens yielding Gram-negative growth in five diagnostic laboratories in the UK. We sought also to compare locally and centrally determined MICs of meropenem and ceftazidime/avibactam. Methods Positive growth from up to 2000 urine specimens per laboratory was plated onto chromID® CARBA SMART agar. Suspected CPE colonies were tested locally by Etest for susceptibility to meropenem and ceftazidime/avibactam, and referred to central laboratories for PCR confirmation of CPE status and microbroth MIC determination. Results Twenty-two suspected CPE were identified from 7504 urine specimens. Ten were confirmed by PCR to have NDM (5), IMP (2), KPC (2) or OXA-48-like (1) carbapenemases. Locally determined ceftazidime/avibactam MICs showed complete categorical agreement with those determined centrally by microbroth methodology. The seven ceftazidime/avibactam-resistant isolates (MICs ≥256 mg/L) had NDM or IMP metallo-carbapenemases. Conclusions The frequency of confirmed CPE among Gram-negative urinary isolates was low, at 0.13% (10/7504), but CPE were found in urines at all five participating sites and the diversity of carbapenemase genes detected reflected the complex epidemiology of CPE in the UK. These data can inform local policies about the cost-effectiveness and clinical value of testing Gram-negative bacteria from urine specimens routinely against a carbapenem as part of patient management and/or infection prevention and control strategies.

Summary Pseudomonas aeruginosa with decreased levels of meropenem susceptibility were identified in the Royal Infirmary Edinburgh in 2002. Within the affected group of patients, none had meropenem-resistant P. aeruginosa when they arrived in the intensive care unit (ICU). Seven isolates from the ICU were collected five months after the decreased susceptibility to meropenem was identified. In order to investigate if resistance was a problem in P. aeruginosa throughout Edinburgh, both in hospital- and community-acquired isolates, a prospective study was performed. The susceptibilities of 104 P. aeruginosa to imipenem, meropenem, ceftazidime, piperacillin/tazobactam and ciprofloxacin were investigated. Meropenem had the highest activity against these isolates and the lowest MIC90 (2 mg/L), followed by imipenem (4 mg/L), ciprofloxacin (8 mg/L), piperacillin/tazobactam (16 mg/L) and ceftazidime (32 mg/L). These isolates were also analysed genotypically by pulsed-field gel electrophoresis. Five of the seven ICU isolates were identified, one isolate was 98% similar and the other was 85% similar to the ICU isolates. One isolate from the prospective study had approximately 90% genotype similarity to the six ICU isolates with ≥98% similarity. There was no clonality within the strains from the prospective study and clusters with >90% similarity comprised at five or less isolates. Isolates with the same resistance patterns did not necessarily have the same genotypic profile. Strains isolated from different patients on the same day were also not necessarily related. The conclusions of this study were that while the seven ICU isolates were clonal or highly related, they were not widespread throughout Edinburgh and the P. aeruginosa within Edinburgh were highly varied.

Mixed populations of Pseudomonas aeruginosa, comprising a carbapenem-susceptible and a carbapenem-resistant strain, containing either the IMP or VIM β-lactamases, were exposed to imipenem. They developed resistance to both imipenem and meropenem. When the same mixed populations were exposed to meropenem, only the mixture containing the VIM β-lactamases became resistant to both carbapenems.