Detection of high-risk carbapenem-resistant Klebsiella pneumoniae and Enterobacter cloacae isolates using volatile molecular profiles

摘要

Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are alarming in the clinical setting, as CRE isolates often exhibit resistance to most clinically-available antibiotics. Klebsiella pneumoniae carbapenemase (KPC) is the most common carbapenemase carried by CRE in North America and Europe, frequently detected in isolates of K . pneumoniae , Escherichia coli , and Enterobacter cloacae . Notably, KPC-expressing strains often arise from clonal lineages, with sequence type 258 (ST258) representing the dominant lineage in K . pneumoniae , ST131 in E . coli , and ST78 and ST171 in E . cloacae . Prior studies have demonstrated that carbapenem-resistant K . pneumoniae differs from carbapenem-susceptible K . pneumoniae at both the transcriptomic and soluble metabolomic levels. In the present study, we sought to determine whether carbapenem-resistant and carbapenem-susceptible isolates of K . pneumoniae , E . coli , and E . cloacae produce distinct volatile metabolic profiles. We were able to identify a volatile metabolic fingerprint that could discriminate between CRE and non-CRE with an area under the receiver operating characteristic curve (AUROC) as high as 0.912. Species-specific AUROCs were as high as 0.988 for K . pneumoniae and 1.000 for E . cloacae . Paradoxically, curing of KPC-expressing plasmids from a subset of K . pneumoniae isolates further accentuated the metabolic differences observed between ST258 and non-ST258.