Are our attempts to contain CPE going down the drain?

I posted recently on the potential risk of CPE contamination of sinks, drains, and hospital wastewater. The question in my mind then was whether contamination is a smoking gun or innocent bystander regarding CPE transmission? What we really need is an intervention to show that better management of sinks and drains results in reduce CPE transmission. And now, we have one! The findings suggest that attempts to control CPE will go down the drain if we don’t intervene to improvement the management of sinks and drains.

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Looking back on a CPE plasmid attack in the Northwest of England

A genomic study of 44 isolates of CPE from various species identified between 2008 and 2010, mainly from the Northwest of England, has concluded that plasmids played a key role in the early dissemination of CPE.

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Promiscuous plasmids: a rapid reflection from ECCMID 2017

I came to ECCMID 2017 with a very specific question: do we need to think beyond ‘same-bug-same-gene’ horizontal transmission from a practical IPC view point in order to address the threat of IPC? The answer, unfortuantely, is yes!

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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.

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KPC Casanova carbapenemase

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The risk of interspecies transmission of carbapenemase genes is a real concern. We can barely get our heads around many different types of carbapenemase in a whole host of Gram-negative bacteria (compare the relative simplicity of methicillin resistance in S. aureus: a single gene, in a single species). Throw in interspecies horizontal transmission of carbapenemases and things get really tricky! Do we implement different control strategies to try to interrupt the transmission of carbapenemases (in contrast to the organisms themselves)? Could you have a multispecies outbreak of a carbapenemase on your hands and not even realise it?

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Is CRE lurking in nursing homes?

Nursing home CRE

They say that things come in threes, so following hot on the heels of blogs about MRSA and other MDROs in nursing homes, I was struck by a recent outbreak report of CRE associated with nursing homes the Netherlands.

Following the admission of a patient from a Greek ICU, a nosocomial transmission of CRE (ST258 KPC K. pneumoniae) occurred. By the way, this occurred despite the hospital recognising the risk of CRE at the time of admission from the Greek ICU, perform an admission screening and implementing pre-emptive contact precautions. Then the index patient was transferred to a nursing home, where subsequent transmission occurred to four other patients.

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CRE “trafficking” plasmids through hospital surfaces

A team from the NIH Clinical Center in the US present a fascinating study, exploring the transmission of carbapenemase-encoding plasmids in unprecedented detail. The intro does a good job of introducing the ‘triple threat’ from CRE: pan-drug resistance, sharply increasing prevalence, and the potential for the horizontal transfer of carbapenemase genes between Enterobacteriaceae species. They introduce the idea of “plasmid trafficking”, which evokes images of shady bacteria dealing in antibiotic resistance genes (a la the infamous cartoon below):

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NIH is a hospital that takes CRE seriously, after being stung by an outbreak in 2011. A quick look at who they screen for CRE illustrates just how seriously they take the threat:

  • ICU / high-risk patients screened twice weekly.
  • All patients screened monthly.
  • Admissions from other hospitals screened for CRE…twice (and given pre-emptive contact precautions until negative cultures are confirmed, for good measure).

They also performed some environmental sampling and recovered several CRE from the hospital environment. This will surprise some, but Enterobacteriaceae do have the potential to survive on surfaces for longer than you may expect.

Surveillance cultures identified 10 patients with KPC-producing Enterobacteriaceae and environmental surveillance identified 6 KPC-producing Enterobacteriaceae. They combined these with several historic isolates from the 2011 outbreak, and a couple of imported isolates to give a sample size of 20 isolates. They wanted to dig deeper into these isolates to explore whether or not they shared any plasmids. And here’s where it gets rather complicated. Conventional whole genome sequencing produces many short reads (100-500 bp) but these cannot distinguish between plasmids and chromosome-encoded genes. Therefore, the authors used a technique called single-molecule, real-time (SMRT) to generate longer reads (around 1000 bp) that make it possible to distinguish between plasmids and chromosome-encoded genes. [I know that I’ve over-simplified this clever genomics massively – but I’ll quickly get out of my depth otherwise!]

The report presents a picture of rare patient-to-patient nosocomial transmission (only 1 of 10 patients were thought to be in-hospital acquisitions), continual importation of diverse CRE, and a complex network of even more diverse plasmids. To illustrate the diversity, one strain of CRE contained no fewer than three distinct KPC-encoding plasmids!

The authors find some evidence of environmental spread of carbapenemase-encoding plasmids, with the carbapenemase-encoding plasmid from a patient matching plasmids recovered from different species of Enterobacteriaceae found in the patient’s environment. What the authors did not demonstrate is transmission of carbapenemase-encoding plasmids from the environment to patients – but I wouldn’t want to be admitted to a room with CRE lurking in the hospital environment!

There’s quite a bit of science around the horizontal transmission of plasmids within biofilms. Combine this with the recent finding of biofilms on dry hospital surfaces, and you have a concerning new angle on how CRE may be transmitted in hospitals.

Image credit. Nick Kim, with permission.

Article citation: Conlan S, Thomas PJ, Deming C et al. Single-molecule sequencing to track plasmid diversity of hospital-associated carbapenemase-producing Enterobacteriaceae. Sci Transl Med 2014; 6: 254ra126.