An unusual and interesting outbreak of CPE was published recently in Clinical Infectious Diseases. Several key points: don’t rely solely on a PCR detecting the “Big 5” carbapenemases (NDM, KPC, OXA-48, IMP, VIM) – at some point you need to test for phenotypic carbapenemase activity; WGS can really help us in unravelling complex transmission routes; and covert plasmid propagation within and between species is a reality.
A recent US study has investigated CPE contamination of sinks, drains, and wastewater. Carbapenemase-producing bacteria were identified throughout the drainage and water system, from drains in patient rooms, right through to wastewater sampled through manholes adjacent to the hospital. My main question in all of this is whether this huge reservoir of carbapenemases in hospital wastewater is a risk for patients. The lack of genetic similarity between isolates in hospital wastewater and isolates from patients suggest not, but I suspect there’s an indirect link and these carbapenemases find their way into isolates affecting humans, which is supported by genetic links between the plasmids carrying the carbapenemases.
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!
I am currently involved in some research that requires a clear distinction between CPE (i.e. Enterobacteriaceae that produce a carbapenemase) and non-carbapenemase-producing CRE. Since ‘non-carbapenemease-producing carbapenem-resistant Enterobacteriaceae’ is a bit of a mouthful, I need to come up with some sort of acronym. I would appreciate your thoughts on the scheme set out below:
You can read more thoughts on acronyms for carbapenem-resistant bacteria in a previous post here.
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.
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?
European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) project
The EuSCAPE project aimed to improve understanding of the occurrence and spread of CPE. LINK
About European Antibiotic Awareness Day
European Antibiotic Awareness Day is a European health initiative coordinated by ECDC which aims to provide a platform and support for national campaigns on the prudent use of antibiotics. Each year across Europe, the European Antibiotic Awareness Day is marked by national campaigns on the prudent use of antibiotics during the week of 18 November. Prudent use means only using antibiotics when they are needed, with the correct dose, dosage intervals and duration of the course. Follow the European Antibiotic Awareness Day: #EAAD. http://antibiotic.ecdc.europa.eu
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The World Health Organization is leading a global campaign for the first World Antibiotic Awareness Week with the slogan “Antibiotics: Handle with Care”. The campaign calls on individuals, governments and health and agriculture professionals to take action to address this urgent health problem. The first World Antibiotic Awareness Week will take place on 16-22 November. Follow the World Antibiotic Awareness Week: #AntibioticResistance. www.who.int/drugresistance.
Carbapenemase-producing organisms (including CPE) present important clinical challenges: the “triple threat” of high levels of antibiotic resistance, virulence, and potential for rapid spread (locally, regionally, nationally, and globally)! However, these organisms somewhat ironically also present challenges to detection in the clinical laboratory. You’d expect that since these organisms are so important clinically they’d be dead easy to detect in the clinical lab – but this isn’t the case.
A comprehensive review published in Clinical Microbiology Reviews provides an overview of the diagnostic approaches to detect carbapenemase producers in the clinical lab. Figures 6 and 7 of the review provide a useful overview of the two broad approaches you could take: culturing organisms on agar plates, or using nucleic acid amplification techniques (NAAT – most commonly PCR) directly from a rectal swab.
I have thought a lot (probably too much) about the best way to describe the issue of carbapenem resistance in Enterobacteriaceae. I decided ages ago that CRE (a la the CDC) is the way to go as a generic term to describe the problem. But the more I think about it, the more I am coming around to the idea that CPE (a la PHE) is better. And here’s why:
- The real issue from a clinical and infection control viewpoint is CPE. Enterobacteriaceae that are resistant to carbapenems by means other than an acquired carbapenemase (i.e. CRE that are not carbapenemase producers) are important, but they don’t seem to have the same capacity to spread as carbapenemase producers.
- It’s a really confusing situation in terms of terminology. From the “end user” staff member on the front line and patient, all that really counts is whether it is a CPE or not. It’s really rather confusing to tell a patient that the have a “CRE that is also a carbapenemase producer” – easier just to say “you have a CPE”. (I accept that you will also need to tell a patient if they have a CRE that is not a carbapenemase producer – but I think this way around is easier.)
- CPE is already en vogue in the UK (mainly due to the PHE Toolkit) so using any other term risks confusion at the time of patient transfer. (Clearly, this point is reversed if you are working in the US!)
I still think that “CRO/CPO” is not the way to go, given the gulf in epidemiology between the Enterobacteriaceae and the non-fermenters (although, sometimes, begrudgingly, you have to go there). What I mean by this is that you will sometimes detect a carbapenemase gene from a PCR but don’t yet know whether it is from a non-fermenter or Enterobacteriaceae species. In this circumstance, this has to go down as a ‘CPO’.
So, there you have it, a personal U-turn. CRE -> CPE. But I wonder whether CDC and PHE and the international community will ever agree a common term…