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We aim to characterise multiple ertapenem-resistant (ERT-R, n = 15) Enterobacteriaceae isolates identified as presumptive carbapenemase producers in a Portuguese hospital in a short period of time (March–July 2010). Antibiotic susceptibility patterns, β-lactamases, genetic relatedness [pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST)], plasmid content and major enterobacterial porins were investigated. Ertapenem resistance was associated with deficiencies in major porins and, in some cases, extended-spectrum β-lactamase (ESBL) or AmpC β-lactamase production among outbreak and non-outbreak clones. Most isolates (n = 8) corresponded to two ERT-R Klebsiella pneumoniae ST15 PFGE-types: (i) a sporadic variant (Kp-A-ERT, n = 1) presenting a premature stop codon in ompK36 and (ii) an epidemic variant (Kp-B-ERT, n = 7) exhibiting a new OmpK36 porin …