Characterization of carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream isolates at a Taiwanese hospital: Clinical impacts of lowered breakpoints for carbapenems

This study was conducted in order to characterize carbapenem-nonsusceptible Klebsiella pneumoniae isolates and to evaluate the impacts of recently lowered interpretative breakpoints for carbapenems for Enterobacteriaceae. Among 152K. pneumoniae bloodstream isolates suspected as AmpC or extended-spectrum β-lactamase (ESBL) producers, 58 (38.2%) isolates were currently interpreted as nonsusceptible to ertapenem, imipenem, or meropenem, and 42 (72.4%) of them were categorized as carbapenemsusceptible by the previous criteria. The high revision rate was associated with the predominance (79.3%) of DHA-1 among the carbapenem-nonsusceptible isolates due to both polyclonal and clonal spread. ESBLs were common (~57%) in both ertapenem-susceptible and -nonsusceptible isolates; however, 84.8% of the carbapenem-nonsusceptible isolates were also AmpC producers. The IMP-8 metallo-β-lactamase was detected in three isolates. Polyacrylamide gel electrophoresis suggested decreased OmpK35 expression in all but one ertapenem-nonsusceptible isolate, and genetic disruptions of ompK35 and ompK36 were detected in 30 and six ertapenemnonsusceptible isolates, respectively. A comparison between patients infected by AmpC- or ESBL-producing ertapenemsusceptible (n062) isolates and those with isolates revised as ertapenem-nonsusceptible (n041) revealed more cases of malignancies (36.6% versus 14.5%; p=0.01) and higher Charlson score (p=0.033) among the patients with ertapenemnonsusceptible isolates; however, the acquisition of an isolate revised as carbapenem-nonsusceptible was not identified as an independent mortality risk factor.