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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.

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