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Carbapenem-resistant Enterobacteriaceae (CRE) have been defined as carbapenem-nonsusceptible and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca. Some exclude ertapenem resistance from the definition.
As of 2013 hard-to-treat or untreatable infections of carbapenem-resistant Enterobacteriaceae (CRE), also known as carbapenemase-producing Enterobacteriaceae (CPE), were increasing among patients in medical facilities. CRE are resistant to nearly all available antibiotics.
The concern is that carbapenem is often used as a drug of last resort when battling resistant bacterial strains. New slight mutations could result in infections for which healthcare professionals can do very little, if anything, to treat patients with resistant organisms. A number of mechanisms cause carbapenem resistance in the Enterobacteriaceae.
PZ-601 is a carbapenem antibiotic currently being tested as having a broad spectrum of activity including strains resistant to other carbapenems. Despite early Phase II promise, Novartis (who acquired PZ-601 in a merger deal with Protez Pharmaceuticals) recently dropped PZ-601, citing a high rate of adverse events in testing.
Nacubactam is an investigational β-lactamase inhibitor being developed for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae (CRE). It belongs to the diazabicyclooctane (DBO) class of compounds and exhibits a dual mechanism of action.
The infection was identified as a carbapenem-resistant Klebsiella pneumoniae strain bearing the novel gene bla NDM-1. The authors concluded that the new resistance mechanism "clearly arose in India, but there are few data arising from India to suggest how widespread it is". [15]
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Among the most concerning resistant pathogens are Carbapenem-resistant Enterobacteriaceae (CRE), Methicillin-resistant Staphylococcus aureus (MRSA), and Clostridioides difficile (C. diff), all of which continue to be responsible for severe healthcare-associated infections (HAIs).