The carbapenemase is out there

truth

A PNAS paper on the genomic diversity of carbapenemase producing bacteria in the US reports strong evidence of carbapenamase (an enzyme produced by bacteria that breaks down carabapenem antibiotics) activity but no sign of a carbapenemase gene. This provides a timely reminder that we are only really scratching the surface in our understanding of carbapenemases and how they work.

It is great to see PNAS publishing this detailed genomic evaluation of CPE. Isolates were collected over 16 months from 4 US hospitals: 3 in Boston (on the East coast), and one from California (in the West). A fairly random selection of isolates from earlier years was also included. They also collected carbapenem-susceptible isolates as species and time-matched ‘controls’. I was unable to find details on the selection criteria for the isolates – exactly how were they selected? Do they represent all CPE, or just some? Also, importantly, what screening was in place in the different hospitals, because this will bear heavily on one of the outcomes of the study: the number of genotypically related clusters identified.

The sample size is pretty small, with a total of 55 carbapenem-resistant Enterobacteriaceae included. KPC was the most common carbapenemase, accounting for 36 (65%) of the CPE, and K. pneumoniae was the most common species identified. A known mechanisms of carbapenem resistance (either by means of a carbapenemase or other mechanisms) could not be identified in 7 (13%) of the 55 isolates. In two of these 7, the team established that plasmid content could transform a sensitive bacterium into a resistant one, suggesting that a plasmid-mediated carbapenemase was responsible. However, despite extensive digging into the genomic material, nothing that looked like a functional carbapnemase could be found, suggesting a novel mechanism could be at play. The study also looked at the potential for horizontal gene transfer, making the case that the identification of transponons with related sequences flanking carbapenemases is evidence of recent horizontal transfer.

The study is useful in highlighting the limitations of our current level of understanding around carbapenemases, and probably argues for a pragmatic approach based on phenotypic identification of carbapenem resistance, supplemented by genotypic methods. For example, the finding of novel/unusual mechanisms of carbapenemase resistance certainly argues against using a PCR kit with primers for 4 or 5 carbapenemases without concurrent phenotypic culture.

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3 thoughts on “The carbapenemase is out there

  1. So if I am understanding this correctly, our current methodology can still identify CPE or CRE but the mechanism for the resistance is not always clear. That will impact the study of resistance transmission but can it also impact clinical management?

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  2. Agree with Jon that this is a very elegant and sophisticatd analysis, but …….. the epidemiological inferences also require an elegant and sophisticated data/sample collection. It looks like these were (consecutive?) isolates from clinical cultures, over a considerable time peiod, that had not very obvious epidemiological linkage. I get the impression that these represent the tip of the iceberg, as the non-infected carriers were not included.
    In the last sentence of their discussion they state: “However, studies based on clinical cultures from hospitalized patients alone are insufficient to fully identify and interrupt transmission; therefore, we must extend these studies further to include isolates from outside of tertiary hospital settings and from asymptomatic carriers.”

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  3. “However, despite extensive digging into the genomic material, nothing that looked like a functional carbapnemase could be found, suggesting a novel mechanism could be at play.”.

    If there was no evidence of a carbapenemase gene, would this imply that there are other mechanisms of resistance to carabapenem antibiotics at play?

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