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):

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.